Some thoughts on the conceptual immune system of the “Synthesis”

As noted in Bad Takes #3, there is a long tradition of dismissing internalist-structuralist thinking on the false grounds that such ideas are necessarily appeals to teleology or mystical inner urges. If an alternative theory can be dismissed in this manner a priori, as an absurdity, then no further effort is required: no complex theoretical modeling is required, no time-consuming experiments, and no difficult analyses of empirical data. Instead, one simply considers a caricature of the alternative theory, dismisses it as absurd, and goes back to assuming that selection is the ultimate source of meaning and explanation in biology.

Indeed, a key part of the conceptual immune system of the neo-Darwinian thought-collective is a series of facile arguments, each representing some type of excluded-middle or false-dilemma fallacy.

To reject thisArgue against this versionIgnoring this version
SaltationEvolution only takes leaps; new features must arise fully formedEvolution normally includes steps or jumps reflecting distinctive variations
CatastrophismThe emergence of key innovations or higher taxa requires catastrophes (revolutions)Non-normal catastrophes play a disproportionate role in major evolutionary episodes
MutationismEvolution is driven by mutation pressure without selectionThe timing and character of evolutionary change strongly reflects the timing and character of mutation events
OrthogenesisEvolution moves in a pre-determined straight line due to mystical inner urgesThe course of evolution strongly reflects mutational-developmental channeling of variation

In the long history of evolutionary thinking, one can find examples in which authors advocate, or seem to advocate, ideas in both the second and third columns. If our aim is to identify, explore and evaluate theories about how the world really works, we are naturally drawn to the best version of a theory, not the stupid version most easily knocked down by facile arguments, i.e., a genuine approach to scientific inquiry entails a focus on the third column.

However, if we want to understand how a thought-collective perpetuates itself decade after decade, we need to understand propaganda. Within the neo-Darwinian thought-collective, the focus is on arguments against the theories in the second column, used to reject what Dawkins calls the “doomed rivals” of neo-Darwinism. In Synthesis propaganda, these excluded-middle arguments are used to maintain the all-important TINA doctrine: There Is No Alternative.

In a healthy and diverse intellectual environment, excluded-middle fallacies have no power. However, the Synthesis created an intellectual monoculture. Within this monoculture, the labels for alternative views were repeatedly associated with bad ideas and subjected to ridicule, turning the labels into bogeymen (a bogeyman is an imaginary creature invoked by adults to scare children into compliance). Through ridicule and the fear of ridicule, the system inhibits alternative thinking and preserves the appearance, if not the substance, of a neo-Darwinian status quo. The conceptual immune system is working when gatekeepers use these terms to shut down debate, but the system also works via self-censorship: well meaning scientists, fearing they will be ridiculed as extremists— or merely fearing they will be misunderstood—, avoid using historically correct terminology like “saltation” or “mutationism” or “neo-Darwinism”, and avoid making accurate references to historic debates.


Orthogenesis appears to be the most successful bogeyman, e.g., the wikipedia page for Orthogenesis repeatedly misleads readers by suggesting that orthogenesis is intrinsically teleological or non-materialistic, in spite of the fact that the article cites, and even directly quotes, multiple scholarly sources that rebut this tendentious linkage. On the talk page, the main author refers bluntly to “God-directed evolution towards a preplanned final goal, which is what orthogenesis is about.” But this is not what orthogenesis is about. Scholarly sources cited in the article (Levit and Olsson; Ulett; Popov; Gould; Schrepfer) repeatedly identify orthogenesis as a general theory about directions that emerge from tendencies of variation, and indicate that the term has been used with a range of views from mystical and teleological to fully materialistic, with well known scientists like Cope or Eimer representing the more respectable materialistic versions. That is, historical scholars describe a general theory, but wikipedians under the influence of Synthesis culture sense that the reason the world needs a wikipedia article on orthogenesis is to serve the conceptual immune system of neo-Darwinism by documenting the foolishness of alternative views.

Self-censorship is well illustrated by scientists who reject gradualism but distance themselves from terms like “saltation” or “macromutation.” For instance, Arthur (2004), after making clear he is a saltationist, e.g., like Goldschmidt, reassures readers he wants to “make clear I am not a ‘saltationist’ like Goldschmidt” (p. 107). Orr and Coyne (1992) utterly ransacked the historic Synthesis case for gradualism yet they say this:

“We hasten to add, however, that we are not ‘macromutationists’ who believe that adaptations are nearly always based on major genes. The neo-Darwinian view could well be correct. It is almost certainly true, however, that some adaptations involve many genes of small effect and others involve major genes. The question we address is, How often does adaptation involve a major gene?”

But under natura non facit saltum, the answer to how often major-effect mutations contribute to adaptation is “almost never,” which (as Orr and Coyne already know) is incorrect. Note that one of the authors of Orr and Coyne (1992) went on to become the go-to defender of orthodoxy for science reporters (see below), and the other eventually went in the opposite direction, citing Bateson approvingly and dismissing gradualism as “little more than a mathematical convenience” (Orr, 2005). Maybe that is why the paper is at war with itself.

Svensson (2023) is deploying the conceptual immune system in the following passage:

Given the strong experimental and empirical evidence against directed mutations (Lenski and Mittler 1993; Futuyma 2017; Svensson and Berger 2019) and the failure of the early mutationists to appreciate the power of natural selection, it is astonishing that some contemporary evolutionary biologists are pushing for a revival of mutationism or mutation-driven evolution (Stoltzfus 2006; Nei 2013; Stoltzfus and Cable 2014). Mutationism was closely connected to the theory of orthogenesis…

Here Svensson encourages readers to join him in scoffing at scientists by linking them to 3 different bogeymen, none of which features in the cited works by Stoltzfus (2006), Nei 2013 and Stoltzfus and Cable (2014).[1] These authors all treat “mutationism” sympathetically, but none rejects the power of selection, e.g., the title of Stoltzfus (2006) is literally “Mutationism and the dual causation of evolutionary change”. None of these pieces invokes directed mutation or advocates what readers would recognize as orthogenesis (i.e., the excluded extreme): Svensson is simply fabricating links to two more bogeymen to increase the chances of ridicule. The piece by Stoltzfus and Cable (2014) is not science but a lengthy historical analysis that debunks the mutationism myth being employed by Svensson in the same sentence.

Importantly, the main clause in the first sentence above from Svensson does not refer to a scientific theory but to persons “pushing for revival.” That is, Svensson does not say that a scientific position is wrong, nor does Svensson express “astonishment” at an idea, but instead the author expresses astonishment at the behavior of persons, i.e., the grammar of the sentence indicates that this is an overt attempt at personal shaming. The “pushing for revival” rhetoric also misrepresents the 3 cited sources, e.g., here is the final paragraph of Stoltzfus (2006):

Nei clearly conceives of his own thinking as “neo-Mutationism”, i.e., something different from historic mutationism, and his main focus is on explaining new thinking and applying it to molecular evolution rather than engaging in historical debates. Stoltzfus and Cable (2014) argue, based on a scholarly analysis of the views of Morgan, Bateson, de Vries and Punnett, that contemporary thinking is closer to their ecumenical view than to neo-Darwinism, i.e., not pushing for revival but reporting on a retreat from a former orthodoxy, one that is easily documented (see The shift to mutationism is documented in our language).

Though the “pushing for revival” rhetoric is false and unscientific, it represents a skillful use of rhetoric by Svensson: he is directly tapping into the conceptual immune system, relying on the fact that his readers have been trained to respond with aversion to the words “mutationism”, “orthogenesis” and “directed mutation.”

Role in Synthesis tribalism

Sometimes, references to the strawman versions of non-Darwinian theories are not focused on ridiculing outsiders or doubters, but on rallying followers to align with their tribal identity. For instance, consider Futuyma (2015):

The seeming exclusivity of the ES [Evolutionary Synthesis] can be understood (and excused, if deemed necessary) only by appreciating the state of evolutionary discourse in the early twentieth century (see Simpson 1944; Rensch 1959; Bowler 1983; Reif et al. 2000). Darwinism was in “eclipse” (Huxley 1942; Bowler 1983), in that almost no biologists accepted natural selection as a significant agent of evolution. (The exceptions were chiefly some of the naturalists.)… Hugo de Vries and Thomas Hunt Morgan, founders of genetics, instead interpreted mutations as a sufficient cause of evolution… [omitted comments on Lamarckism and orthogenesis]… Those who today disparage the Evolutionary Synthesis as a constrained, dogmatic assertion that evolution consists only of natural selection on random genetic mutations within species must recognize that the authors of the Synthesis were responding to an almost complete repudiation of natural selection, adaptation, and coherent connection of macroevolution to these processes.

As an argument about scientific history, this is a chain of fallacies.[1] The first fallacy is that critics of neo-Darwinism such as de Vries and Morgan denied the agency and importance of selection, or that they accepted mutations as a sufficient basis of evolution. But let us suppose that critics of neo-Darwinism denied selection: how does that justify or explain the architects making selection all-important, the exclusive source of order and direction? Wouldn’t it have been wiser to counter the extremists with a more moderate position? That makes two fallacies. Now, set aside those two fallacies, i.e., suppose that critics denied selection and that this somehow justifies advocacy of an opposing extreme. Where does that leave us today? We now have a choice of two extreme theories, neither of which fits the evidence. The logical choice is to declare both of these dinosaurs extinct, right? Given that “excusing” is something we do for people not for theories, why does Futuyma make this a matter of literally “excusing” dead people? And given that we are called on to forgive, why does Futuyma conclude that we must direct out sympathy to one specific group of extremists rather than both?

Of course, the appeal of Futuyma’s rhetoric is based on tribalism, not logic. Synthesis Historiography tells us that, before the Great Synthesis unified the kingdom, bringing a period of peace and prosperity, there was an era of chaos and darkness called The Eclipse, when the light of Darwin was absent, with constant war between the tribes of Lamarckians, Darwinians, mutationists, orthogenesists and saltationists. In order to unify the kingdom and return the throne to the House of Darwin (the rightful rulers), the knights of the Synthesis had to purge the anti-Darwinians, who behave irrationally and hold views with obvious flaws. That is, the origin story for the Synthesis tribe has a historic battle in which the good guys use reason and evidence to beat the bad guys whose heads are full of nonsense.

In the passage quoted above, Futuyma is calling on the power of these shared cultural tropes, naming The Eclipse and all the classic bogeymen— Lamarckism, saltations, orthogenesis and mutationism— to remind tribal members which side they are on: the good guys fighting against the benighted enemies of Darwin and selection. Thus Futuyma skillfully manipulates in-group readers using a shared mythology, with arguments that will seem bizarrely illogical to an outsider.

Capturing the middle ground for Darwin

In most contexts, the system of false-dilemma arguments suffices to maintain ideological conformity and rally the faithful. However, sometimes there are doubters or rebels or merely ordinary scientists who stumble on an unorthodox result and wonder if there might be something of value in alternatives to neo-Darwinism.

In this case, gatekeepers must offer a more sophisticated argument. One common approach is appropriation: conceding some aspect of the alternative view, but describing it in different language, grounding it in familiar sources and associating it with illustrious ancestors, and insisting that this actually part of the mainstream tradition and is not the same thing as any historical alternative to neo-Darwinism.

For instance, when confronted with evidence that evolution may sometimes reflect developmental channeling of variation, the guardians of orthodoxy may admit that the evidence exists, but insist that it is not very compelling, that this is definitely not orthogenesis, and anyway, that this possibility was foreseen by Darwin’s apostles and disciples, therefore it is already part of tribal culture. Futuyma (2017) makes this type of appropriation argument, citing the following passage from Mayr:

“Every group of animals is ‘predisposed’ to vary in certain of its structures, and to be amazingly stable in others . . . Only part of these differences can be explained by the differences in selection pressures to which the organisms are exposed; the remainder are due to the developmental and evolutionary limitation set by the organisms’ genotype and its epigenetic system . . . the epigenotype sets severe limits to the phenotypic expression of such [random] mutations; it restricts the phenotypic potential. The understanding of this limitation facilitates the understanding of evolutionary parallelism and polyphyletic evolution.”

Mayr (1963) p. 608

A better historic source to cite for this idea would have been Eimer or indeed, dozens of other non-Darwinian scientists who advocated much more forcefully for a role of internal developmental biases. However, to cite Eimer would be to go outside the Synthesis tradition.

Mayr typically was disdainful of internalist theories and evo-devo— he said the developmentalists were “hopelessly confused” because they didn’t understand that development is just a proximate cause—, and he repeatedly invoked the contrary neo-Darwinian position that, because natural populations have infinite variability, when the same thing happens twice in evolution, this must be because it is the uniquely apt solution. In the above passage, Mayr appears to have gone off-script (his meaning is not precisely clear: one could interpret this as a statement about epistatic effects mediated by selection). However, Futuyma, (2017) is happy to accept the above statement as justification to fully appropriate developmental bias on behalf of the Synthesis tradition. He literally writes, “The idea that development can influence the direction of evolution was fully congenial to the architects of the ES.” Note that this is a statement about people and not about scientific theories, i.e., there is no explanation of how developmental bias follows from the shifting gene frequencies theory, or why Mayr was wrong to reject developmentalist arguments in the 1980s and 1990s. He does not even attempt such a theoretical reconciliation (for an attempt, see Amundson 2005 or Scholl and Pigliucci 2010). He quotes some people and declares on this basis that the case is closed. He is not defending any theory of causation, but defending the fullness and authority of tradition.

Even as a claim about tradition, the notion that the architects of the Modern Synthesis were “fully congenial” to the idea of internal dispositions is clearly false. For evo-devo people who fought for respectability against Synthesis gatekeepers, this must feel like gaslighting. Mayr is merely stating an idea in vague terms. He doesn’t actually use the key word “direction” in the cited passage, which is important (for those of us who think about these things) because it leaves open whether he is allowing directionally biased effects (more up than down) or merely dimensional effects (more trait 1 than 2). We can’t tell because this is just hand-waving and Mayr has not provided an explicit theory that would clarify such issues. When scientists are serious about an idea, they typically invest intellectual labor in exploring, applying, and defending an idea, clarifying their own thinking, and making important distinctions (e.g., think of how Simpson or Mayr developed terminology for modes of speciation or evolutionary rates). Did Mayr publish any research on internal dispositions? Did he inspire an evo-devo research program with his forceful advocacy of developmental bias? Did he offer a terminology to recognize different classes of bias? No, none of that. A more accurate description of historical sources would be that some of the architects toyed with orthogenesis-adjacent ideas while (more typically) advocating for the standard neo-Darwinian view that, because variation is abundant in all directions, systematic patterns reflect selection and not variation.

Let’s return to the issue of gradualism vs. saltationism. At one extreme is the position of natura non facit salta, i.e., nature does not take leaps. Thinkers such as Fisher and Darwin thought that, for practical purposes, all evolutionary changes are composed from infinitesimal effects. Darwin said that his theory would “absolutely break down” if any organ could not have been formed by a succession of infinitesimal changes. The intermediate position of historic saltationists such as Bateson and T.H. Huxley is that evolution has some jumps. The contrary extreme from gradualism, in which evolution is (for practical purposes) all large jumps, is found only as a strawman theory.

As explained in Why size matters, the gradualist position is not arbitrary for neo-Darwinism and other views that assume empirical adaptationism. If selection and variation are like the potter and the clay, with variation merely providing raw materials and selection providing shape and direction, then variation has to be composed of fine particles. If all change is small, it is possible to argue that selection governs evolution and can do anything, working from infinitesimal variation in every trait. But if evolutionary change comes in chunks, this immediately takes something out of the control of selection—the character and timing of discrete variations—, and then we need some kind of theory for the character and timing of variations in order to have a workable theory of evolution.

In other words, empirical adaptationism necessarily provokes theories of gradualism (in the sense of infinitesimalism). This is not just a logical conclusion, it is how scholars such as Beatty or Gould have reconstructed the actual development of Darwin’s thinking. Likewise, the empirical conclusion that saltations actually occur in evolution provokes the search for internalist theories that address the generation of non-infinitesimal variations. This is not just a logical conclusion, it is why Bateson cataloged distinctive variations in order to study evolution.

Darwin provided some early examples of the excluded-middle arguments outlined above. In his writings, he nearly always embellishes his case against discrete evolutionary steps by referring to them with dramatic language as “monstrosities”:

I reflected much on the chance of favorable monstrosities (i.e., great and sudden variations) arising. I have, of course, no objection to this, indeed it would be a great aid, but I did not allude [in OOS] to the subject for, after much labor, I could find nothing which satisfied me of the probability of such occurrences. There seems to me in almost every case too much, too complex, and too beautiful adaptation, in every structure, to believe in its sudden production.

Why “great and sudden”? Why not “modest”? Why not “medium-sized and sudden”? Describing saltations in provocative and negative language is a common rhetorical trick, e.g., Wright associates them literally with “miracles”:

“From assisting Prof. Castle, I learned at firsthand the efficacy of mass selection in changing permanently a character subject merely to quantitative variability. Because of this and a distaste for miracles in science, I started with full acceptance of Darwin’s contention that evolution depends mainly on quantitative variability rather than on favorable major mutations. ” (Wright S. 1978. The Relation Of Livestock Breeding To Theories Of Evolution. Journal Of Animal Science 46:1192-200.)

Note that Wright misrepresents Darwin’s position as calling for “mainly” rather than exclusively quantitative variability, i.e., natura non facit saltum.

This reliance on strawman arguments and misdirection sometimes makes it difficult to determine what Darwin’s followers actually believe. Clearly they are against monstrosities, but how large of a non-monstrosity will they tolerate? Clearly Wright is against miracles and for quantitative variability, but what exactly does that mean? When gradualism fails, will he claim that there are no miracles and insist he was right all along?

Today the issue has been turned on its head. Saltationism is now the mainstream view, but “saltationism” is still presented as the straw-man theory that all evolutionary changes are dramatic leaps, or in which major taxon-defining traits must appear in a single step (e.g., Coyne). As we have seen, the contemporary scientists who conclude in favor of saltationism on empirical or theoretical grounds insist that they are not saltationists, and they sincerely hold the erroneous belief that they are aligned with Darwin and historical neo-Darwinism.

This is what happens when people absorb the TINA doctrine, i.e., they learn the lesson that neo-Darwinism is just what is reasonable, and all the alternatives are crazy, without learning neo-Darwinism as a substantive falsifiable position. Scientists are typically agile thinkers, great at making up rationalizations: if you train them to accept that gradualism is right, they will find some way to make it right, based on whatever assumptions and definitions yield the approved conclusion. For instance, note how the issue is framed by researchers cited by Chouard:

Many researchers have welcomed the return to favour of large-effect mutations and have resurrected Goldschmidt’s long reviled idea of the hopeful monster. But they can’t ignore the small-effect mutations. “We need much more data before the issue of large versus small can be settled”, says Coyne. Kingsley, like Coyne favours a middle-ground view, in which neither large- nor small-effect mutations are ruled out. “Our work has too often been portrayed as saying that Darwin was wrong” about big leaps in adaptation, he says. But in fact, none of the traits his group has studied is completely due to the effects of a single gene.

Instead of defending the all-small position of genuine neo-Darwinian gradualism, the traditionalists now defend the not-all-large (i.e., some-small) position that one “can’t ignore the small-effect mutations.”

Likewise, in response to Shapiro’s criticism that molecular saltations speak against Darwinism, Dean (2012) objects thus:

His stance is patently unfair. Thomas Huxley famously criticized Darwin for championing too gradualist a view of phenotypic evolution. Today’s Darwinists accept Huxley’s criticism . . . Horizontal gene transfer, symbiotic genome fusions, massive genome restructuring (to remarkably little phenotypic effect in day lilies and muntjac deer), and dramatic phenotypic changes based on only a few amino acid replacements are just some of the supposedly non-Darwinian phenomena routinely studied by Darwinists.

Notice the charge of being “unfair.” Here the author has gone all the way to a purely cultural position on neo-Darwinism: there is no fixed scientific theory attached to the brand, only a cultural tradition consisting of people (Darwinians) whose beliefs may change at any time. If the right sort of people start studying saltations or invoking them, this makes saltations part of neo-Darwinism.


I could go on, but these examples should be sufficient to make the point about how the conceptual immune system works. Excluded-middle arguments based on ridicule are the first line of defense, but when scientists stumble upon the middle ground, traditionalists will claim it for tradition, even if this involves misrepresenting history and shifting the goal-posts. When apologists for tradition shift from merely rejecting strawmen to appropriating the excluded middle on behalf of tradition, this represents a genuine scientific shift that is masked by conservative rhetoric. Being able to see through the misleading rhetoric is a skill that can be learned. In the current climate of evolutionary discourse, it is a necessary skill.

Another necessary skill is courage. The secret power of the conceptual immune system is that the excluded-middle arguments rely on ridicule delivered by gatekeepers, and the aura of ridicule remains when scientists discover the excluded middle.[2] Scientists want to be respected, not ridiculed, by their peers: this threat is enough to cow most of them into voluntarily making the wrong association, in order to avoid disrespect. If you use terms like “saltation”, “orthogenesis” or “mutationism” positively (or invoke “neo-Darwinism” negatively) even if your usage is historically correct and accurate, this guarantees that you will be subjected to knee-jerk reactions of ridicule, or you will be accused of seeking attention using inflammatory rhetoric. Clearly the past generation of scientists was afraid of saying such words even when they are perfectly apt and reasonable.[3] I hope that current and future generations will not be so fearful.


  • Arthur W. 2004. Biased Embryos and Evolution. Cambridge: Cambridge University Press.
  • Dean (2012) Review of Evolution: a View from the 21st Century. Microbe Magazine (available via the wayback)
  • Gould SJ. 2002. The Structure of Evolutionary Theory. Cambridge, Massachusetts: Harvard University Press.
  • Levit GS, Olsson L. 2006. “Evolution on Rails”: Mechanisms and Levels of Orthogenesis. Annals for the History and Philosophy of Biology 11: 97-136.
  • Mayr E. 1963. Animal Species and Evolution. Cambridge, Massachusetts: Harvard University Press.
  • Orr HA, Coyne JA. 1992. The Genetics of Adaptation: A Reassessment. American Naturalist 140:725-742.
  • Popov I. 2009. The problem of constraints on variation, from Darwin to the present. Ludus Vitalis 17:201-220.
  • Ulett MA. 2014. Making the case for orthogenesis: The popularization of definitely directed evolution (1890–1926). Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences 45:124-132.


[1] For a takedown of this passage from Futuyma, see Stoltzfus (2017). Critics of neo-Darwinism typically objected to its two main vulnerabilities, natura non facit saltum and the dichotomy of roles in which selection is the potter and variation is the clay. In every alternative to neo-Darwinism, the variation-generating process plays a dispositional role. Note that, in attempting to understand what critics of neo-Darwinism believe, one must not mistake skepticism about the quality and rigor of selective explanations for doubts about the (in principle) power of selection. Bateson did not deny selection as a true cause responsible for adaptation, but he was so jaded he thought that selective explanations would always be inaccessible to scientific proof and would remain mere armchair speculation. Nei seems to have a similar position.

[2] Because ridicule is such a strong demotivator, maintaining conformity does not require a large class of aggressive gatekeepers a la Svensson. A little bit goes a long way. As explained in the introductory paragraphs, most people don’t need to be shamed directly to avoid thinking unorthodox thoughts, they will just do it on their own because, again, people want to be respected.

[3] Note that accurately depicting mutationism, neo-Darwinism, or other historic views does not require any special courage for historians or other scholars who are not striving for, and are not dependent on, the approval of mainstream Synthesis culture. Among mainstream evolutionary thinkers, Allen Orr has shown courage in quoting Bateson approvingly and in depicting gradualism correctly as an extreme position. Gould was unafraid to show sympathy to non-Darwinian thinking, but his sympathy seems more like pity when one notices how frequently Gould associates critics of neo-Darwinism (e.g., de Vries, Goldschmidt, Bateson) with behavioral disorders, reinforcing the Synthesis tribal mythology in which only crazy people reject neo-Darwinism.

Bad takes #2. Evolution by “mutation pressure”

Unfamiliar ideas are often mis-identified and mis-characterized. It takes time for a new idea to be sufficiently familiar that it can be debated meaningfully. We look forward to those more meaningful debates. Until then, fending off bad takes is the order of the day! See the Bad Takes Index.

In his equally entertaining and obnoxious piece “The frailty of adaptive hypotheses for the origins of organismal complexity,” Lynch (2007) writes

The notion that mutation pressure can be a driving force in evolution is not new (6, 24–31)

citing works of Darwin, Morgan, Dover, Nei, Cavalier-Smith, and Stoltzfus and Yampolsky.

What does it mean to invoke evolutionary change due to a driving force of mutation pressure? This language suggests a process of population transformation by the mutational conversion of individuals, in contrast to population transformation by reproductive replacement.

That is, in a simplified world of discretely inherited types, we can imagine two general ways to transform a reproducing population from mainly type A to mainly type B. One mode is for an initially rare type B to take over the A population, over many generations, by the cumulative effects of differential reproduction, either biased (selection) or unbiased (drift). Individuals of type B over-produce, while A individuals die out, so that A individuals are replaced by unrelated B individuals. This is usually how we think about the transformation of populations: reproductive replacement. Selection and drift are often listed as the two main causes of evolution, and they act by reproductive replacement.

A second possible mode of change is for a population of predominantly A individuals to change by many separate events of A-to-B conversion (either individual conversion, or the cross-generational conversion of a lineage from parent to offspring). In this case, A individuals are lost, not by death, but by conversion, and likewise, B individuals are over-produced, not by the excess reproduction of B parents, but by conversion from A individuals. This process might take a single generation or many generations, depending on the rate of conversion (see image for a simulation).

A simulation of evolution by mutation pressure (from the mutation pressure page developed by John McDonald). N = 20 red squares at left represent individuals, with offspring generations going to the right. The reproductive variance is 0, so each individual leaves exactly 1 offspring in the next generation, inheriting the parental state or a mutated state with u = 0.025. By 100 generations, the population is mostly transformed, by mutational conversion alone, without reproductive differences.

In a more complex scenario, there are other possibilities. For instance, given diploid inheritance we could consider a process of biased gene conversion by which A1A2 genotypes are converted into A2A2. Suppose that A2 is recessive so that A1A1 and A1A2 have phenotype P1, and A2A2 has P2. In this scenario, biased gene conversion can transform a predominantly P1 population into a P2 population. Dover’s ideas about molecular drive combine effects of conversion and replacement.

One of the minor theories in Darwin’s Origin of Species is the mass transformation of individuals by direct effects of the environment. This idea was not unique to Darwin, but simply reflected 19th-century thinking by which heredity is (in effect) mediated by responsive memory-fluids that circulate in the body: after collecting bodily experiences, the memory-fluids gather in the gametes, and during reproduction, they blend, passing on a blended version of inheritance plus experience. Given this view, it was natural to suppose that, when animals or plants encounter a new environment, this results in a hereditary transformation by the cumulative effect of many environment-induced conversions.

The literature of the pre-Synthesis period includes some (typically ambiguous) references to population transformation by mutational conversion, e.g., Shull (1936) writes

If a given mutation were to happen often enough, and nothing opposed its survival, it could easily spread through the entire species, replacing all the other genes at the same locus.

Evolution by mutation pressure according to Haldane and Fisher

In the broader context of evolutionary theorizing, the mutation pressure theory appears most prominently as a strawman rejected by Haldane (1927, 1932) and Fisher (1930). That is, Haldane and Fisher did not advocate the notion of evolution by mutation pressure, but presented an unworkable theory as a way to reject the idea, popular among critics of neo-Darwinism, that evolutionary tendencies may reflect internal variational tendencies. In reality, the early geneticists typically argued, not for mutational transformation of populations, but for a two-step process of “mutation proposes, selection disposes” (decides); and the idea of orthogenesis was typically an appeal to what we might call “constraints” today. That is, the mutation pressure theory began as a dubious take on internalist thinking.

Regardless, Haldane and Fisher worked out the implications of evolution by mutation pressure, finding it unlikely on the grounds that, because mutation rates are small, mutation is a weak pressure on allele frequencies, easily overcome by opposing selection. Haldane concluded that this pressure would not be important except in the case of neutral characters or abnormally high mutation rates.

The conclusion of Haldane (1927)

To understand what Haldane is doing, one must bear in mind that, in the neo-Darwinian tradition, selection is the model of an evolutionary cause: other factors or processes are considered to be causal only to the extent that they look like selection. What selection does is to shift frequencies (and ultimately drive alleles to fixation), so Darwin’s modern followers define evolution as shifting frequencies and they define causal forces as pressures that might cause fixation. In effect, Haldane equates the importance of mutation with the potential for mutation pressure to drive allele frequencies. In this way of thinking, if mutation-biased evolution is happening, this is because mutation is driving alleles to high frequency against the opposing pressure of selection, which leads to Haldane’s conclusion that either (1) the mutation rate has to be abnormally high, or (2) selection has to be practically absent (i.e., neutrality). Fisher’s (1930) reasoning was similar. From the observed smallness of mutation rates, he drew a sweeping conclusion to the effect that internalist theories are incompatible with population genetics.

Provine (1978) identifies this argument (against evolution by mutation pressure) as one of the key contributions of theoretical population genetics to the Modern Synthesis, because it gave Darwin’s followers a seemingly rigorous basis to reject internalist theories (establishing the core Synthesis principle of There Is No Alternative). The argument was cited repeatedly by the architects of the Modern Synthesis (for examples, see Stoltzfus, 2017), and continues to be cited, e.g., Gould (2002) cites Fisher’s version of the argument and concludes that

Since orthogenesis can only operate when mutation pressure becomes high enough to act as an agent of evolutionary change, empirical data on low mutation rates sound the death-knell of internalism. (p. 510)

Subsequent work has partially undermined the narrow implications of the Haldane-Fisher argument, and completely undermined its broader application as a cudgel against internalism. Mutation pressure is almost never a reasonable cause of population transformation, because it would happen so slowly and take so long that other factors such as drift would intervene, as argued by Kimura (1980). The case studied by Masel and Maughan (2007) is a rare example in which evolution by mutation pressure is reasonable: the authors estimate an aggregate mutation rate of 0.003 for loss of a trait (sporulation) dependent on many loci, concluding that complex traits can be lost in a reasonable period of time due primarily to mutational degradation.

Thus, in spite of what one would conclude from Haldane (1927), patterns of mutation bias in evolution generally do not indicate evolution by mutation pressure via high mutation rates, or via neutral characters. Mutation-biased neutral evolution happens, not because mutation pressure is driving alleles to fixation in a biased way (instead, drift is the cause of fixation), but due to a bias in the origination process. And of course, Yampolsky and Stoltzfus (2001) showed that, when there is a bias in the introduction process, this can impose a bias on the course of evolutionary change even when fixations are selective, i.e., there is no requirement for neutral evolution.

In summary, the classic theory of evolution by mutation pressure is not much use in understanding evolution, and is mainly of historical interest for its role in an influential fallacy: generations of evolutionary thinkers believed wrongly that the mutation pressure theory proves mathematically that internalist theories are incompatible with population genetics.

Other theories

Now, with this background, we may return to Lynch’s bad take, associating various authors with mutation pressure as a driving force. Of the authors cited — Darwin, Morgan, Dover, Nei, Cavalier-Smith and my colleagues and I — none of them directly propose a theory of evolution by mutation pressure. However, the ideas of Darwin and Dover depict a process reliant on mass conversion: in Dover’s case, population transformation takes place by a dual process of conversion (gene conversion or sub-genomic replication) and reproductive replacement, and in Darwin’s case, it takes place by direct inherited effects of the environment.

Nei refers to “mutation-driven” evolution (the title of his 2013 book), but this is not a reference to mutation driving alleles to fixation. Nei’s usage of “drive” is descriptive or explanatory: evolution is mutation-driven to the extent that our understanding of important aspects of the course of evolution relies on knowing which mutations happen at what times. The same meaning is used in “Mutation-Driven Parallel Evolution During Viral Adaptation” (Sackman, et al. 2017). For an explanation of this meaning of “drive,” see Bad Take #4.

Likewise, the work from my colleagues and me is not about evolution by mutation pressure. From the very beginning, we have (1) followed Provine (1978) in noting the historical importance of the Haldane-Fisher argument against evolution by mutation pressure, and (2) promoted a theory for the effects of biases in the introduction process, obviously a different theory because it contradicts the implications of the mutation pressure theory.

So, what on earth does Lynch mean when he refers to evolution driven by mutation pressure? This is unclear. The model that Lynch (2007) presents immediately after the quoted statement is not a model of evolution by mutation pressure in the classic sense of Haldane and Fisher and IMHO does not correspond to what any of the cited authors are trying to say.

To understand what the model tells us, we must analyze it in detail, in comparison to the classic mutation-selection balance (also co-developed by Haldane and Fisher). The forces of population genetics are conceptualized like the laws of statistical physics, as mass-action pressures on allele frequencies due to the aggregate effect of countless individual events. In the case of mutation, countless individual events of mutational conversion from allele A1 to allele A2 result in a force or pressure of mutation shifting quantities of A1 to A2. Because there are innumerable independent events, each with an infinitesimal effect, we can represent the aggregate effect with a continuous quantity, e.g., we can write fA2‘ = fA2 + u fA1 to indicate the increase in fA2 due to mutation at rate u from allele A1, and we can write fA1‘ = (1 – u) fA1 to represent the corresponding reduction in the frequency of allele A1 due to mutation to allele A2.

In the classic conception of the mutation-selection balance, if A1 is favored over A2 by a selection coefficient s, then reproductive replacement by selection represents a pressure of magnitude s increasing fA1 and decreasing fA2, whereas mutation is a pressure of magnitude u with the opposite effect, acting by conversion (rather than reproductive replacement). The equilibrium frequency of A2 is roughly f = u / s, and this is typically a small number (much closer to 0 than to 1) because mutation rates are very small, e.g., a typical rate for a specific nucleotide mutation is 10-9 per generation. This is why Haldane concluded (above) that mutation would be unimportant unless selection is effectively absent (i.e., neutrality) or mutation rates are abnormally large (note how the classical mutation-selection balance of Haldane and Fisher is closely related to their argument about evolution by mutation pressure).

Lynch appears to reach a different solution to the same problem of the equilibrium frequency in a 2-allele system. His equation for the ratio of A1 to A2 is meS, where m is the forward-backward mutation bias favoring A1, and eS is the ratio of fixation probabilities where upper-case S = 2Ngs and lower-case s has the same meaning as above. However, this result actually does not represent the equilibrium frequency of A1 in a population of individuals, as for Haldane-Fisher: instead, it refers to the equilibrium distribution of infinitely many loci subject to an origin-fixation process, where each locus is fixed for A1 or A2, that is, meS is the expected ratio of (1) the fraction of loci fixed for A1 to (2) the fraction of loci fixed for A2.

(Figure 1 of Lynch, 2007)

This is easier to understand with a concrete example: the relative genomic frequency of two synonymous codons like CAT and CAC encoding histidine, where one of the codons (let’s assume CAC) is slightly more favored by selection.

The two cases, classic and Lynch, correspond to the large-population and small-population approximations for the ratio of favored to disfavored codons in Bulmer’s (1991) mutation-selection-drift model. In a large deterministic population, each histidine codon is fixed for the favored synonym (CAC), yet the disfavored codon (CAT) is maintained at low frequency in mutation-selection balance per Haldane-Fisher. In the small population, each histidine codon is fixed for either the favored codon (CAC) or the disfavored codon (CAT), and the frequency distribution of fixed states for loci is determined by the balance of two origin-fixation rates. So, in either case, if the disfavored codon is expected a fraction f of the time, then f is also the expected frequency of that codon over an infinite genomic set of histidine sites.

Thus, Lynch’s argument gives a different result because it refers to a different kind of mass-action pressure than Haldane and Fisher conceived. The relevant pressure in Lynch’s argument is the mass-action pressure due to events of origination aggregated over an infinite distribution of loci (sites). This origination pressure is not the same as classic mutation pressure, which is the mass-action pressure due to mutational conversion events aggregated over infinitely many alleles (in a population) at the same locus.

The result of this pressure (relative to a deterministic universe with only the favored codon), is to ensure that, for small values of S = 2Ngs, a substantial fraction of loci are fixed for the disfavored state; when S = 2Ngs becomes modestly large, this fraction is negligible. That is, mutation pressure, for Lynch, refers to something that ensures the predictable presence of deleterious states. By contrast, the theory of Yampolsky and Stoltzfus (2001) is about the way that biases in origination impose biases on which path, out of many possible, is taken by adaptation.

Clearly this model ensures the presence of deleterious states for small values of S, but it is not clear what justifies Lynch’s framing of this as an effect of a pressure of mutation (more precisely, a pressure of origination), rather than as an effect of random drift or of origin-fixation pressure. Mutation and fixation do not act separately in the context of the argument, and drift is profoundly important in ensuring that, in Lynch’s stochastic anti-paradise, a substantial fraction of everything is in a sub-optimal state. In a world that has deterministic selection, the favored codon always wins (and the disfavored one is never fixed by chance), even in small populations, and this will be true regardless of what we assume about mutation. Metaphorically, mutation is just knocking at the door, offering bad choices: drift has to open the door and let them in. On this basis, Lynch ought to point the finger at drift (not mutation) as the reason for non-optimality.

In fact, this is all utterly misleading when taken in context. After telling the reader that the idea of evolution by mutation pressure is not new, Lynch continues as follows

The notion that mutation pressure can be a driving force in evolution is not new (6, 24–31), and the conditions that must be fulfilled if mutation is to alter the direction of evolution relative to adaptive expectations are readily derived.

This is a sweeping claim about mutation and directionality! Yet, what follows is not a general model of effects of mutation on the direction of evolutionary change, but Bulmer’s model featuring fixations of deleterious alleles! That is, Lynch refers generally to mutational effects altering the “direction” of evolution, yet apparently, given his Manichean worldview, “direction” is just a matter of down vs up in fitness. And we just established that drift, not mutation, is the cause of deleterious fixations, which will happen even if there is no mutation bias (e.g., the disfavored codon will sometimes be fixed, even without any mutation bias). In the end, Lynch has presented correct mathematical results, but framed these results in an incorrect way that can only lead to confusion.

Accordingly, Svensson (here or here) has repeatedly claimed, citing Lynch’s paper, that an effect of mutation bias on adaptation would require “drift in small populations.” This error arises from a literal reading of Lynch, who (1) conflates diverse ideas (including ours) under the heading of evolution by mutation pressure, and then (2) makes a sweeping reference to mutational effects on “direction.” However, as explained, the effect requiring small populations in Lynch’s model is the fixation of a slightly deleterious allele by drift in small populations, whereas arguments about mutation-biased adaptation do not involve fixations of deleterious alleles at all, e.g., the behavior of the Yampolsky-Stoltzfus model does not rely in any sense on the fixation of deleterious alleles by drift.

What is the cause of so much misapprehension? The molecular revolution induced profound changes in thinking that have not been properly processed. Instead, we have attempted to squeeze a new understanding into the same old vocabulary— using old words for new concepts. In some cases, the result is verbal violence, as in the way that “Darwinian adaptation” is now used for the lucky mutant view previously known as a non-Darwinian theory of pre-adaptation. Familiar words are now overloaded with different concepts, and we have not paid attention to the problems caused by this overloading. Evolution by mutation pressure, in the classic Haldane-Fisher sense, means something different than what Lynch’s model means, which is something different than what the Yampolsky-Stoltzfus model means. The forces theory is inadequate, and leads scientists to incorrect conclusions, e.g., the assumption that mutation-biased evolution requires neutrality, which is pervasive in the literature.

The path toward greater clarity depends on making distinctions, e.g., distinguishing the introduction (origination) process from classical mutation pressure (across infinitely many copies of an allele in a population) and from origin pressure (across infinitely many loci). The reason to distinguish these, again, is that they behave differently, so that the rules for reasoning about one kind of causal process are different from the rules for reasoning about another.

Likewise, one must bear in mind that biological processes are not the same as the operators in models or mathematical formalisms, which capture only some of implications of biological processes for evolution. The classic conception of forces in population genetics includes a thing with the label “mutation” (and another thing with the label “selection”), but this thing does not have all the same implications as the biological process with the label “mutation.”

Sources that fail to make such distinctions will mislead readers with the impression that every reference to mutation is a reference to exactly the same evolutionary theory, when this clearly is not the case.


  • Fisher RA. 1930. The Genetical Theory of Natural Selection. London: Oxford University Press.
  • Gould SJ. 2002. The Structure of Evolutionary Theory. Cambridge, Massachusetts: Harvard University Press.
  • Haldane JBS. 1927. A mathematical theory of natural and artificial selection. V. Selection and mutation. Proc. Cam. Phil. Soc. 26:220-230.
  • Haldane JBS. 1932. The Causes of Evolution. New York: Longmans, Green and Co.
  • Haldane JBS. 1933. The part played by recurrent mutation in evolution. Am. Nat. 67:5-19.
  • Kimura M. 1980. Average time until fixation of a mutant allele in a finite population under continued mutation pressure: Studies by analytical, numerical, and pseudo-sampling methods. Proc Natl Acad Sci U S A 77:522-526.
  • Lynch M. 2007. The frailty of adaptive hypotheses for the origins of organismal complexity. Proc Natl Acad Sci U S A 104 Suppl 1:8597-8604.
  • Provine WB. 1978. The role of mathematical population geneticists in the evolutionary synthesis of the 1930s and 1940s. Stud Hist Biol. 2:167-192.
  • Shull AF. 1936. Evolution. New York: McGraw-Hill.
  • Stoltzfus A. 2006. Mutationism and the Dual Causation of Evolutionary Change. Evol Dev 8:304-317.
  • Yampolsky LY, Stoltzfus A. 2001. Bias in the introduction of variation as an orienting factor in evolution. Evol Dev 3:73-83.


Biased gene conversion is a newly recognized population-genetic force, non-identical with mutation, selection, or recombination. BGC is a conversion mechanism, not a replacement mechanism, but the formula for BGC is A1 + A2 –> A2 + A2, whereas the mutation formula is A1 –> A2. Similarly, the crossing-over formula is A1B1 + A2B2 –> A1B2 + A2B1. Thus, although the molecular operation of gene conversion is associated with cross-overs and with the machinery for recombination, the genetic operation of BGC is not the same thing as recombination.

Bad takes #4. Attacking the phrase “mutation-driven.”

Unfamiliar ideas are often mis-identified and mis-characterized. It takes time for a new idea to be sufficiently familiar that it can be debated meaningfully. We look forward to those more meaningful debates. Until then, fending off bad takes is the order of the day! See the Bad Takes Index.

In regard to reports of mutational biases influencing the changes involved in molecular adaptation, Svensson and Berger (2019) write

Despite the importance of mutations in these two studies, we emphasize that selection ultimately drove these adaptive allele frequency changes, rather than evolution being ‘mutation-driven’ as some might claim [1,7,8,13].

Actually the “mutation-driven” language is advocated in reference #1 (Nei’s book), but not in the other 3 sources cited.

The authors object that, whereas the term “drive” refers to a cause that drives an allele to fixation, the changes implicated in the cited studies reflect selective fixation rather than fixation by mutation. The implication is that sources 1, 7, 8 and 13 advocate a theory of population transformation, not by reproductive replacement (via selection or drift), but by mutation pressure, i.e., the cumulative effect of many events of mutational conversion, which is generally a bad idea for reasons pointed out by Kimura (1980), although there are rare cases where it makes sense, e.g., loss of a complex character (for a more thorough explanation, see Bad take #2).

But of course, fixation by mutation pressure is not the theory advocated in Nei’s 2013 book Mutation-Driven Evolution, nor the other sources cited, nor sources such as:

Sackman AM, McGee LW, Morrison AJ, Pierce J, Anisman J, Hamilton H, Sanderbeck S, Newman C, Rokyta DR. 2017. Mutation-Driven Parallel Evolution During Viral Adaptation. Mol Biol Evol. 34:3243-3253

Nor is this what Pennings, et al. (2022) mean when they clarify that “our study is focused on the dynamics of adaptation and reversal in the context of point mutation-driven, stepwise evolution, rather than evolution through horizontal gene transfer or plasmid conjugation”. Nor is this what Tenaillon (2014) means when he writes

“In particular, the long-term evolution of 12 replicate populations of Escherichia coli by R.E. Lenski unraveled a succession of mutation fixations that reached up to 10 % fitness effect (Lenski & Travisano 1994). Large effect mutations appeared therefore to be the drivers of adaptation.”

One must remember that the piece by Svensson and Berger (2019) is not a serious scholarly analysis, but a parody of bad Synthesis apologetics, a Sokal’s hoax exposing that— when the topic is either post-modernist cultural analysis or the status of evolutionary theory— it is possible to “publish an article liberally salted with nonsense if (a) it sounded good and (b) it flattered the editors’ ideological preconceptions.”

With their cheeky “mutation-driven” objection, the authors are parodying a bad-faith argument that does not address any genuine issue of dispute, but is simply a way to score points with the kind of guileless reader who thinks Masatoshi Nei needs a lesson in basic population genetics.

If we take away this false pretense, the remaining issue is semantic: should we (1) restrict “mutation-driven” only to the case in which mutation is a cause of allele fixation, i.e., the mutation pressure theory of evolution, or (2) allow an additional meaning of “driving” that seems more explanatory, i.e., evolution is mutation-driven to the extent that the explanation for the character and timing of evolutionary change refers to the character and the timing of mutations.

Which semantic position is justified? The issue is readily resolved by examining how “drive” is used in evolutionary discourse. Does the literature of evolutionary biology include a meaning of “driven” that would justify the use of “mutation-driven”?

In fact, a generic explanatory meaning for “drive” is well established, e.g., here is just a tiny sample of recent uses from the technical literature:

Population size is clearly a condition, not a change-making causal process. Therefore, whenever we hear our colleagues talking about population size “driving” something, this indicates an explanatory and not causal-mechanistic meaning of “drive.” The non-causal nature is unmistakable in the first example above, because what is being “driven” by population size is model choice, which does not physically exist in the realm of biology, but represents an abstraction in the realm of modeling. A cause X and its direct effect Y must occur in the same place, the locale of causation.

Note that this meaning of “drive” can be used — and often is used — with the concept of selection, i.e., we can talk about selection driving a thing, without that thing being an allele frequency, e.g.,

More generally, based on a purely descriptive analysis of patterns, e.g., a statistical analysis, scientists may refer to the predominant explanatory factor as the factor that “drives” the pattern. In this kind of claim, the implied chain of causation may be absent or unclear. As argued by Green and Jones (2016) in regard to “constraints,” scientists sometimes prefer a non-mechanistic language, because this allows them to discuss formal relations applicable to some system, without having to commit to a (potentially problematic) hypothesis for a mechanistic cause.

This does not mean that all uses of “drive” are equally welcome. When some authors above write that “These properties — and not function — seem to be the forces driving much of protein evolution” they are literally saying that properties are forces, which is gibberish. I find many of these uses of “drive” to be unhelpful, especially when results could be described more clearly using causal language (but see below).

To summarize, in their playful parody of Synthesis sophistry, Erik and David represent the “mutation-driven” issue with a delightfully empty misrepresentation sandwich. The meat is a weak semantic argument to the effect that the word “drive” must refer to population-genetic cause in the classic sense, a mass-action pressure that might cause allele fixation. Examples from the research literature demonstrate conclusively that the word “drive” simply does not have this restriction. This nutrient-poor semantic filling is sandwiched between two misrepresentations of the cited sources: (1) that they advocate the “mutation-driven” language (this is false for 3 of the 4 sources cited), and (2) that they invoke mutation pressure as a cause of fixation (this is false for all 4 sources).

Finally, note that we are having this discussion about language precisely because our customary causal language is insufficient. In the shifting-gene-frequencies theory of the Modern Synthesis, evolutionary causes are mass-action pressures (per statistical physics) that may cause allele fixations, e.g., selection and drift are seen as causes because they are potential causes of fixation. This theory of causes makes no distinction between shifts of a frequency from 0 to 1/N (or 1/(2N)) vs shifts among non-zero frequencies. When Haldane (1927) and Fisher (1930) addressed the potential for mutation-induced trends, they treated mutation as a cause of shifting and dismissed it as unimportant.

We have no other recognized causal language than statistical “forces” (“pressures”) at the population level. In particular, we have no recognized causal language for the effects of the introduction process: such effects are most often mis-described in terms of mutation pressure, or they are described indirectly or passively, as a matter of background conditions. The legacy of neo-Darwinism is that selection is the paradigm of a cause, and any other factor is judged to be causal or not depending on how much it acts like selection. Because the introduction process is not like selection at all, it has not been recognized as a causal process.

Attempts to describe the role of mutation actively rather than passively, with strong verbs, are certain to provoke opposition from the reactionary elements parodied by Svensson and Berger (2019). As I have written elsewhere, this position is cultural, not scientific: the reactionaries are culturally rigid but scientifically flexible. They will accept saltations (non-infinitesimal changes, major-effect alleles) and orthogenesis (tendencies due to internal biases) if the evidence demands it, but they will never endorse the terms “saltation,” “internal biases in evolution” or “orthogenesis,” because this would reveal a heretical departure from tradition. They will not reject mutation-biased adaptation due to biases in the introduction process, but they will describe it with old words while referencing dead authorities, in order to anchor new concepts in traditional sources (see also Bad Takes #5).


Kimura M. 1980. Average time until fixation of a mutant allele in a finite population under continued mutation pressure: Studies by analytical, numerical, and pseudo-sampling methods. Proc Natl Acad Sci U S A 77:522-526.

Bad takes #5. It’s just contingency

Unfamiliar ideas are often mis-identified and mis-characterized. It takes time for a new idea to be sufficiently familiar that it can be debated meaningfully. We look forward to those more meaningful debates. Until then, fending off bad takes is the order of the day! See the Bad Takes Index.

A common “stages of truth” meme holds that successful disruptive ideas are first (1) dismissed as absurd, then (2) resisted— the idea is declared unlikely and the evidence is strenuously disputed—, and finally (3) regarded as trivial and attributed to long tradition. Haldane’s version is that “The process of acceptance will pass through the usual four stages: (i) this is worthless nonsense; (ii) this is an interesting, but perverse, point of view; (iii) this is true, but quite unimportant; (iv) I always said so.” The QuoteInvestigator piece on the stages-of-truth meme has this version:

For it is ever so with any great truth. It must first be opposed, then ridiculed, after a while accepted, and then comes the time to prove that it is not new, and that the credit of it belongs to some one else

Svensson and Berger (2019)— in an article that reads like a Sokal’s hoax of Bad Synthesis Apologetics— model all the stages of truth in the same paper: (1) they dismiss strawman versions (e.g., mutation as an independent cause of adaptation) as absurd (see Bad Takes #3 and Bad Takes #4), (2) they present a clumsy version of the theory but dispute the evidence and declare it implausible based on a fabricated list of population-genetic restrictions, and (3) finally, implicitly admitting that the phenomenon is real and that the theory we proposed is correct, they describe it as trivial and familiar:

These studies therefore only exemplify how historical contingency and mutational history interact with selection during adaptation to novel environments [31, 38, 52], entirely in line with standard evolutionary theory and the uncontroversial insight that different genomic regions contribute differentially to adaptation driven by selection, with mutations merely providing the genetic input [53].

In this way, the reader is guided through the stages of truth from patent absurdity to yesterday’s news.

However, our focus here is only on the end-point of this progression, in which Svensson and Berger (2019) give the impression that the new work on mutation-biased adaptation represents ordinary textbook knowledge, so that these new results induce no changes in evolutionary reasoning, raise no new questions, and suggest no new priorities for research. The specific implication of the passage above is that these findings are merely a matter of “contingency” and present nothing original or new relative to the contents of references 31, 38 and 52.

[figure legend: A recent exploration of “contingency” by Wong (2019), revealing the lack of a precise meaning other than something vaguely to do with chanciness.]

Yet contingency is not a causal theory: it is an explanatory concept indicating that a system is non-equilibrium, so that the state of the system cannot be predicted without knowing the initial conditions and detailed dynamics. The notion of contingency, by itself, does not provide a theory of the dynamics. If we try to answer the odd question, “what does contingency predict about how the mutation spectrum shapes the spectrum of adaptive substitutions?” then we will get nowhere without a theory for the dynamics, and this theory will not be about contingency (an explanatory concept, not a cause of anything), but about the dynamical issue of how the details of mutation rates influence the spectrum of adaptive substitutions.

Svensson and Berger have a bad habit of misrepresenting cited works. What do refs 31, 38 and 52 say? References 31 and 38 are from the field of quantitative genetics, and simply do not provide any such dynamical theory, e.g., here is the abstract to reference 31:

The introduction and rapid spread of Drosophila subobscura in the New World two decades ago provide an opportunity to determine the predictability and rate of evolution of a geographic cline. In ancestral Old World populations, wing length increases clinally with latitude. In North American populations, no wing length cline was detected one decade after the introduction. After two decades, however, a cline has evolved and largely converged on the ancestral cline. The rate of morphological evolution on a continental scale is very fast, relative even to rates measured within local populations. Nevertheless, different wing sections dominate the New versus Old World clines. Thus, the evolution of geographic variation in wing length has been predictable, but the means by which the cline is achieved is contingent.

Reference 52 is Good, et al (2017), a deep sequencing study of samples from Lenski’s LTEE (long-term evolution experiment). This is mainly an empirical analysis of allele trajectories and clonal interference and so on. There are no explicit claims for an effect of mutation bias on the spectrum of adaptive substitutions (mutation bias is mentioned only in relation to mutators, but mutators generate a lot of hitch-hikers in this experiment, so that the influence of mutators on the set of adaptive changes is not clearly established). Indeed, the presentation of results indicates in various places (e.g., the comments on parallelism) that Good et al are not paying attention to the issue of how mutation bias influences probabilities of beneficial changes.

What is going on here? Svensson and Berger (2019) seem intent on illustrating how to avoid addressing the novelty of (1) a formal pop-gen theory that focuses on the introduction process, and which makes novel predictions about evolution based on tendencies of variation (addressing aspects of parallelism, trends, GP maps, findability, etc), in a way that directly contradicts the classic Haldane-Fisher “mutation pressure” argument, and (2) empirical results confirming a distinctive prediction of this theory, namely effects of mutation biases on adaptation (not requiring neutrality or high mutation rates), contradicting a long neo-Darwinian tradition of dismissing internal biases in evolution.

One way to avoid these key issues is to engage in whataboutery, i.e., responding to an issue by demanding attention to a second issue. What about other research? What about selection? Whataboutery provides the writer an opportunity to engage the reader on some related topic, e.g., for purposes of name-dropping. Rather than taking the opportunity to educate readers on the details of a new and exciting — but poorly known — body of work on mutation bias and molecular adaptation, i.e., rather than covering the studies that are the topic of their commentary, Svensson and Berger instead lavish their attention on older and much better known work on related topics by eminent scientists, e.g., the LTEE from Lenski and colleagues, lizard stuff from Jonathan Losos, the famous stickleback Pitx1 example, or David Houle’s work on fly wings.

More generally, Svensson and Berger (2019) illustrate how Synthesis apologists do not contemplate the practice of science in terms of falsifiable theories, precise reasoning, or the prospect of striking future discoveries, but are mainly concerned with crafting a narrative of traditions made of people, vague ideas, and flexible themes. They trivialize new work by assigning it to familiar and vague categories that make it seem ordinary, rather than mapping it to the specific issues that motivate it, make it significant, and raise unanswered questions for the future.

Model of Bell’s first telephone from 1875

To understand how this game works, consider a completely unrelated example, namely the invention of a telephone 150 years ago (image). The novelty-hating curmudgeon may object as follows: You say there is something new here? How arrogant to make such a claim! There is nothing new here at all! This is merely an engineered device, and inventors have been crafting devices for centuries! I could show you 15 devices from just the past few years that are more impressive than this one, with more parts. You have done nothing to acknowledge this past work. Have you no respect? There is no fundamentally new technology here, merely pieces of wood and metal and wire! I could build something like this in an afternoon for $25. There are no new electrical or mechanical principles at work, merely electrical currents and vibrations controlled by magnets. It looks like other devices I have seen. I could break it easily with a hammer. I doubt that it can fly like an airplane.

The problem is not that these objections are false statements. They could all be true. The problem is that they fail to address the crucial issue: the telephone prototype instantiates a generalizable technology to support remote voice communication through wires, thus over long distances.

Svensson and Berger have done an excellent job of illustrating how to play the irrelevant-objections-to-novelty game. When they argue that new work on mutation-biased adaptation is just another example of contingency, this represents the strategy of describing new work in a trivially general way, like saying that the first telephone is just a device. When they claim that the theory we proposed is already part of the Modern Synthesis, on the grounds that it can be broken down into familiar parts, this is like objecting that the telephone is made of familiar parts and therefore cannot be new.

Of course, the significance of a new device— or a new theory— is not in the list of parts, but in what the assembled whole accomplishes.

What is the actual significance of recent work on mutation-biased adaptation? The essence of neo-Darwinism is a dichotomy of variation and selection, in which variation merely provides raw materials (substance, not form), and selection is the source of order, shape, and direction. Theories of evolution subject to internal biases directly contradict neo-Darwinism and were considered heretical. The argument of Haldane and Fisher that such theories are incompatible with population genetics (see Bad takes #2) was eagerly adopted by the architects of modern neo-Darwinism, yet (1) this classic conclusion is unwarranted theoretically and (2) its implications are refuted empirically. These two provocative claims are established by recent work on mutation-biased adaptation; they are not part of textbook knowledge; they are not established in well known studies cited by Svensson and Berger to illustrate scientific name-dropping.


Good BH, McDonald MJ, Barrick JE, Lenski RE, Desai MM. 2017. The dynamics of molecular evolution over 60,000 generations. Nature 551:45-50.

Bad takes #3. Mutation bias as an independent cause of adaptation.

Unfamiliar ideas are often mis-identified and mis-characterized. It takes time for a new idea to be sufficiently familiar that it can be debated meaningfully. We look forward to those more meaningful debates. Until then, fending off bad takes is the order of the day! See the Bad Takes Index.

Svensson and Berger (2019) begin their opinion piece with a multifarious attack on the theory that mutation bias is “adaptive in its own right” or “an independent force” or something that “can explain the origin of adaptations independently of, or in addition to, natural selection.” They enthusiastically invoke versions of this theory in 5 different places, just on the first page (yellow highlights)!

They associate this theory with the line of argument on mutation bias and adaptation developed in work from my group (e.g., Yampolsky and Stoltzfus, 2001; Stoltzfus, 2006a, 2006b, 2012, 2019), and extended by studies such as:

None of these sources promote or assume a theory of mutation bias as an independent cause of adaptation, or a theory of mutation being adaptive in its own right. For instance, in the original twin-peaks model of Yampolsky and Stoltzfus (2001), the peak favored by the higher selection coefficient is accessible only via a lower mutation rate, and vice versa. Stoltzfus and Norris (2015) worked very hard to establish that— contrary to lore— transitions and transversions that change amino acids hardly differ in their fitness effects.

Thus, whereas some other authors have promoted the idea of adaptive mutation (e.g., Cairns, Caporale, Rosenberg), “natural genetic engineering” (Shapiro) or merely some statistical correlations between mutational patterns and fitness effects (Monroe, et al. 2022), the above sources do none of those things. Thus, Svensson and Berger (2019) are illustrating the concept of a strawman argument, criticizing an alternative view by relying on a false representation of that view.

The strawman argument of Svensson and Berger, 2019. The authors use this figure to misrepresent the theory of Yampolsky and Stoltzfus (2001), representing the hypothesis of mutation as an “independent cause of adaptation” by a thick arrow with a question mark. The other parts of this figure are intended to represent conventional thinking.

This form of this strawman argument has a long history. Repeatedly, critics of neo-Darwinism have suggested that observed tendencies or directions of evolutionary change cannot be explained solely by selection, but reflect internal aspects of mutation or development, and advocates of neo-Darwinism have responded by accusing these critics of proposing some form of directed mutation or adaptive mutation, or of engaging in mysticism or teleology. Is this simply a case of intellectual dishonesty? Perhaps, but a more sympathetic view is that this is an error in reasoning induced by an ideology that recognizes only one kind of directionality, so that every argument about directions (e.g., in phenotype space) is treated as an argument about intrinsically adaptive directions.

Because Darwin’s followers have used this strawman argument for over a century, we know how the advocates of internalist theories respond:

“I take exception here only to the implication that a definite variation tendency must be considered to be teleological because it is not ‘orderless.’ I venture to assert that variation is sometimes orderly and at other times rather disorderly, and that the one is just as free from teleology as the other. In our aversion to the old teleology, so effectually banished from science by Darwin, we should not forget that the world is full of order . . . If a designer sets limits to variation in order to reach a definite end, the direction of events is teleological; but if organization and the laws of development exclude some lines of variation and favor others, there is certainly nothing supernatural in this” (Whitman, 1919: see p. 385 of Gould, 2002)

In general, when we find that false arguments are maintained and nurtured for generations, this is because they are being used, not to resolve substantive scientific questions, but to maintain conformity within a closed ideological system, i.e., advocates of neo-Darwinism use these arguments to help each other avoid thinking any new thoughts, working together to keep the dream alive. Gatekeepers like Svensson and Berger try to discourage new thinking by treating it as bad science and careerism (in this case, with ironic results).

Of course, we must not confuse theories and people, e.g., a theory supported by bad arguments does not become a bad theory for this reason. The theory and its apologetics are two different things. We can define neo-Darwinism clearly in terms of the dichotomy of the potter (selection) and the clay (variation), and this concept stands by itself. Separate from this, there is a culture or a set of rhetorical practices associated with neo-Darwinian apologetics. It is this neo-Darwinian culture or thought-collective that has a sociological aspect and a self-protective urge that gives rise to the same pathologies as any cult or identity-group.

The false accusations of teleology or directed mutation are part of the conceptual immune system of the neo-Darwinian thought-collective (described in a separate post). This kind of strawman is used in two ways. The first line of defense against alternative views is to claim that they are inherently flawed or absurd: they represent mental errors that can be dismissed immediately, not alternative scientific theories that must be evaluated with research. This is what neo-Darwinians teach about history: the neo-Darwinian view is simply the rational evidence-based approach to evolution, whereas critics behave irrationally and hold views with obvious flaws.

Eventually, however, some of the more intellectually rigorous ones begin to sense that scientific theories are supposed to stand for something substantive and risky, and they begin to consider the plausibility of alternative ideas. In this case, the priests of the religion must offer a more sophisticated argument. In this second line of defense, the alternative is granted as a theoretical possibility, but (1) its importance is minimized, and (2) it is described in different language and grounded in the Darwinian faith tradition itself, by reference to obscure passages in the sacred texts. That is, the doubter is shown that the apostles and disciples of olden times, and even the great Lord Darwin himself, also experienced moments of doubt, posed difficult questions, and considered alternative views. The initiate now has a more sophisticated understanding of the faith, which does not demand inner purity, but merely outward piety. In this case, the faith is shown by creating constructive ambiguity that can be used to shift the focus of discussion from new scientific developments backwards to tradition and to the pantheon of heroes.

Svensson and Berger (2019) illustrate both strategies brilliantly. First they attack claims of mutation-biased adaptation by attacking the straw-man of “independent cause of adaptation,” then they present a more reasonable idea based on population genetics— a butchered version of the theory proposed by Yampolsky and Stoltzfus (2001)—, and present this as conventional wisdom. First they state absurdly that the theory is part of the neutral theory— which in their strangely twisted conception of history was somehow swallowed up by the Modern Synthesis— but they cite no source for this, e.g., the theory of Yampolsky and Stoltzfus (2001) appears nowhere in Kimura’s (1983) seminal book on the neutral theory. They also present a derivation of a key equation in Box 1, which gives a short series of mathematical results and names Haldane, Kimura, and Fisher without naming Yampolsky and Stoltzfus, guiding the reader to conclude falsely that the theory comes from famous dead people.

However, at the same that they appropriate the theory on behalf of Fisher, et al., they also purport to undermine it by claiming that it depends on unusual conditions including sign epistasis and drift in small populations (these are not actual requirements, but fabrications intended to make the argument seem more respectable).

For more bad takes on this topic

This is part of a series of posts focusing on bad takes on the topic of biases in the introduction of variation, covering both the theory and the evidence. For more bad takes, see the index to bad takes.


Gould SJ. 2002. The Structure of Evolutionary Theory. Cambridge, Massachusetts: Harvard University Press.

Bad takes #1. We have long known.

Unfamiliar ideas are often mis-identified and mis-characterized. It takes time for a new idea to be sufficiently familiar that it can be debated meaningfully. We look forward to those more meaningful debates. Until then, fending off bad takes is the order of the day! See the Bad Takes Index.

An anonymous reviewer responded to the manuscript of Stoltzfus and Yampolsky (2009) with the claim that “we have long known that mutation is important in evolution,” citing the following passage from Haldane (1932) as if to suggest that the message of our paper (emphasizing the dispositional role of mutation) was old news:

A selector of sufficient knowledge and power might perhaps obtain from the genes at present available in the human species a race combining an average intellect equal to that of Shakespeare with the stature of Carnera. But he could not produce a race of angels. For the moral character or for the wings, he would have to await or produce suitable mutations

We included it in the final version of the paper because, actually, this passage demonstrates the opposite of what the reviewer implies. What is Haldane suggesting?

I can’t resist a good story, so let’s begin with this 1930s photo of Italian boxer Primo Carnera, his friend and fellow heavyweight champ Max Baer, and Hollywood actress Myrna Loy. Baer dated Loy in real life. They made a movie together, the three of them (thus the staged publicity photo). Baer, one of the greatest punchers of all time and half-Jewish, became a hero to a generation of Jewish sports fans when he demolished Max Schmeling, the German champion, prompting Hitler to outlaw boxing with Jews. He literally killed one of his opponents, and repeatedly sent Carnera to the floor during their single fight.

Primo Carnera, Myrna Loy, and Max Baer in a publicity photo from the 1930s

But the point of this picture is that, although Baer was a formidable man, Carnera makes him look small. Other fighters were afraid to get in the ring with him. Though enormous — 30 cm taller and 50 kg heavy than the average Italian of his generation —, Carnera was not the aberrant product of a hormonal imbalance. This photo shows a huge man who is stocky but well proportioned, muscular, and surprisingly lean. Again, he was not a misshapen monster, but a man at the far extremes of a healthy human physique, which is precisely Haldane’s point.

Selective breeding to the quantitative extremes of known human ability, Haldane proposes, could produce a race combining the extreme of Carnera’s magnificent stature with Shakespeare’s magnificent verbal ability.

Haldane contrasts this with a different mode of evolution dependent on new mutations, which might produce a race of angels, if one could wait long enough for the mutations to happen. That is, Haldane is contrasting (1) a mode of evolution that could combine the known extremes of human ability with (2) a mode of evolution that could generate imaginary fictitious not-at-all-real creatures. Haldane, Wright and Fisher each argued that a mode of change dependent on new mutations would be too slow to account for the observed facts of evolution. They argued instead that evolution must take place on the basis of abundant standing variation.

That is, in the passage above, Haldane is not endorsing a mode of mutation-dependent evolution, but gently mocking it, in contrast to a mode of evolution that, based on quantitative standing variation, could produce a race of magnificently eloquent champions.

Thus, the reviewer’s comment was a bad take on Haldane, a misinterpretation of Haldane’s meaning.

In addition, the “we have always known” comment represents a more general category of bad take that substitutes, in place of a specific target of criticism, a much broader, fuzzier, or more generic claim. Note what the reviewer does not say: the reviewer might have said

“The authors’ implicit claim of novelty is preposterous. We have long known about the role of biases in the introduction process emphasized in this manuscript. Haldane (1932) and Fisher (1930) explored the theoretical implications of such biases, and Simpson and Mayr repeatedly incorporated a theory of internal variational trends into their interpretations of the fossil record. The authors must cite these sources instead of suggesting that their arguments are original.”

But of course, the reviewer does not say this, because nothing like this ever happened. Think about it.

Certainly, the reviewer is correct that scientists in the mainstream Modern Synthesis tradition have always known that mutation is important in evolution. More precisely, the importance they assigned to mutation was that it is ultimately necessary, because without mutations, evolution would grind to a halt. Haldane, Fisher, Ford, Huxley, Dobzhansky, and others said this explicitly.

However, they did not say that mutation is important as a dispositional factor. Instead, they argued explicitly against this idea, e.g., Haldane (1927) is the original source of the argument that mutation pressure is a weak force (see Bad takes #2).

The theory of biases in the introduction process, by contrast, says that mutation is important in evolution as a dispositional cause, a cause that makes some outcomes more likely than others, and that this importance is achieved (mechanistically) by way of biases in the introduction process.

So, the reviewer is making an implicit bait-and-switch argument. The theory of biases in the introduction of variation is a specific population-genetic theory with specific conditions and implications, and the reviewer is responding to this by saying “we have always known that mutation is important,” but this is not the same thing: the traditional importance assigned to mutation is not “dispositional cause that makes some outcomes more likely than others” but “ultimate source of raw materials without which evolution would grind to a halt.”

Finally, this bad take is part of a family of bad takes in which the novelty of a claim X is rejected on the grounds that X sounds vaguely like X’, or that X can be categorized as a member of some larger and fuzzier class of claims (see Bad Takes #5: Contingency). This is often the case with “we have long known” arguments. If the theory was in fact old, the reviewer would not have made a vague “we have long known” argument, but would have cited the original source of the theory, e.g., “Of course the theory of biases in the introduction process is not new, because Haldane proposed exactly the same theory 70 years ago and worked out its implications!” In fact, no such antecedent exists, which is why, to defend tradition, the reviewer must resort to a bait-and-switch argument.


Haldane JBS. 1932. The Causes of Evolution. New York: Longmans, Green and Co.

Stoltzfus A, Yampolsky LY. 2009. Climbing mount probable: mutation as a cause of nonrandomness in evolution. J Hered 100:637-647.