The Mutationism Myth: III Foundations of Evolutionary Genetics

 
This is the fifth 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

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The Curious Disconnect

Today in the Curious Disconnect we continue with our series on the Mutationism Myth. In this oft-told story (see part 1), the discovery of genetics in 1900 leads to rejection of Darwin's theory and the rise of "mutationism", a laughable¹ theory that imagines evolution by mutation alone, without selection. "Mutationism" prevails for a generation, until Fisher, Haldane and Wright show that genetics is the missing key to Darwinism. In the conclusion to the story, the world is set right again when the "Modern Synthesis", combining selection with Mendelian genetics, shoulders aside the mutationist heresy, which ends up in the dustbin of history with the other "doomed rivals" of Darwin's great theory.²

Thats the story, at least. In reality- as we found out in part 2-, the Mendelians rejected Darwin's errant principles of heredity, not his principle of selection. What kind of view did the Mendelians develop? Addressing this question is our next challenge. Today, in part 3, we'll consider aspects of the Mendelian view that became the foundations of mainstream 20th-century thinking. In part 4, we'll delve into some "non-Darwinian" or "anti-Darwinian" aspects that were rejected, or merely ignored.

The Mutationism Myth. 3. Foundations of evolutionary genetics

Darwin's "Natural Selection" theory posited a smooth and automatic process of adaptation to altered conditions, dependent on infinitesimal hereditary fluctuations ("indefinite variability", in Darwin's terminology) induced by the effect of "altered conditions of life" on the "sexual organs". As we discovered in part 2, geneticists rejected fluctuation because it is incompatible with the assumption of exclusively Mendelian inheritance, an assumption embraced eagerly by geneticists, and held in suspicion by others for many years. As Bateson wrote:

"To Darwin the question, What is a variation? presented no difficulties. Any difference between parent and offspring was a variation. Now we have to be more precise. First we must, as de Vries has shown, distinguish real, genetic, variation from fluctuational variations, due to environmental and other accidents, which cannot be transmitted." (p. 95)

and as Morgan wrote:

"As has been explained, the kind of variability on which Darwin based his theory of natural selection can no longer be used in support of that theory, because, in the first place, in so far as fluctuating variations are due to environmental effect, these differences are now known not to be inherited, and because, in the second place, selection of the differences between individuals, due to the then existing genetic variants, while changing the number of individuals of a given kind, will not introduce anything new. The essential [feature] of the evolutionary process is the occurrence of new characteristics." p. 148-149 of Morgan (1932) ³

Because heredity and variation did not behave in the manner assumed by Darwin and his followers, it was up to a new generation of evolutionists to develop a new understanding of evolution. Thus, at a time when naturalists were dismissing genetics and clinging to 19th-century views of heredity, including Darwinism and Lamarckism, a group of Young Turks⁴ was laying the foundations of the genetics-based understanding of evolution that dominated the 20th century.

The concept of population genetics

To understand these foundations, I need to say a few words about the theoretical side of evolutionary genetics, often referred to as "population genetics". Please recall from Theory vs. Theory that when we talk about population genetics theory or music theory, thats a different sense of "theory" from Lamarck's theory or the prion theory of disease. Previously, we called them theory₂ (body of abstract principles) and theory₁ (grand conjecture).

Population genetics theory₂ (roughly speaking) works out the implications of transmission genetics in populations of reproducing organisms, focusing on implications of such Mendelian phenomena as biparental inheritance, chromosome assortment, mutation, recombination, sex-linked inheritance, and so on.

As it exists today, population genetics theory₂ covers a wide range of possible worlds, and thus a wide range of possible theories₁. For instance, it provides classic equations to treat allele frequencies continuously and deterministically (e.g., Hardy-Weinberg), and at the same time, it provides another framework for addressing probabilistic changes with random drift. Is evolution deterministic or probabilistic? Population genetics theory₂ doesn't say- it allows us to consider both possibilities. Is evolutionary change smooth or does it come in chunks? Population genetics theory₂ doesn't say: it provides a quantitative genetics framework for continuous changes in quantitative characters, and a completely different framework for molecular evolutionists examining discrete characters. There are limiting cases where these different frameworks converge in some respects, but there is not any single realizable world in which all of population genetics theory₂ applies, thus theoretical population genetics can't be understood as a theory₁.

Crudely speaking, three frameworks of population genetics theory have been important in the 20th century: the stability analysis⁵ of systems of continuous allele frequencies, initially deterministic a la Hardy-Weinberg (or Lewontin-Kojima and so on) and later stochastic; the "quantitative genetics" theory of generational change in continuous-valued phenotypic characters (with implicit genetics) subject to selection; and the dynamics of the steady-state origin-fixation process, which was not an important paradigm until Kimura proposed the neutral theory.

The Bateson-Saunders equilibrium

In a landmark 1902 report to the Evolution committee of the Royal Society, Bateson and Saunders report some of their own findings and, more generally, try to explain the new science of Mendelian genetics, and the implications of Mendel's rules for evolution. In one of many fascinating comments, Bateson and Saunders suggeest that:

"It will be of great interest to study the statistics of such a population [with recognizable Mendelian characters] in nature. If the degree of dominance can be experimentally determined, or the heterozygote recognised, and we can suppose that all forms mate together with equal freedom and fertility, and that there is no natural selection in respect of the allelomorphs, it should be possible to predict the proportions of the several components of the population with some accuracy. Conversely, departures from the calculated result would then throw no little light on the influence of disturbing factors, selection, and the like.

Those of you who know your population genetics will recognize, in this passage, a paradigm that continues to play a key role in contemporary research as a "zero-force" model, describing the case of an unperturbed system, i.e., a system at rest. Deviations from this resting state indicate the perturbing effect of some factor or force.

In 1908, Hardy and Weinberg independently derived solutions for the frequencies of genotypes and alleles in the zero-force model of Bateson and Saunders. The mathematical solution to the Hardy-Weinberg equilibrium, as it came to be called, is sufficiently trivial that publishing it was nearly beneath the dignity of G.H. Hardy, the archetypal pure mathematician. In his paper, Hardy seems to sneer at biologists, saying "I should have expected the very simple point which I wish to make to have been familiar to biologists". Legend has it that Hardy learned of this problem while playing cricket with Punnett, the Mendelian, providing an early example of how interdisciplinary work is done.

The research program that eventually developed around this model was exactly as Bateson and Saunders imagined: compute the Hardy-Weinberg equilibrium, compare this to the observed frequencies, then interpret any deviations in terms of "the influence of disturbing factors". Researchers continue to use it, as one may find by searching PubMed with "hardy-weinberg AND 2009 [date]", which yields 532 publications for 2009. Contemporary philosophers discussing causation in evolutionary theory make frequent reference to Hardy-Weinberg as a zero-force law (see Stephens, 2001).

Given the crystal-clear statement of the problem by Bateson and Saunders, including the assumptions and the interpretive framework, should we not call it the Bateson-Saunders-Hardy-Weinberg equilibrium (or the Bateson-Saunders-Weinberg equilibrium, saving Hardy the embarrassment of receiving credit for something practical ⁶)?

Morgan's origin-fixation process

An entirely different, but similarly prescient, model is found in T.H. Morgan's 1916 book:

"If through a mutation a character appears that is neither advantageous nor disadvantageous, but indifferent, the chance that it may become established in the race is extremely small, although by good luck such a thing may occur rarely. It makes no difference whether the character in question is a dominant or a recessive one, the chance of its becoming established is exactly the same. If through a mutation a character appears that has an injurious effect, however slight this may be, it has practically no chance of becoming established.
If through a mutation a character appears that has a beneficial influence on the individual, the chance that the individual will survive is increased, not only for itself, but for all of its descendants that come to inherit this character. It is this increase in the number of individuals possessing a particular character, that might have an influence on the course of evolution." (187-189)

This is an abbreviated framework for understanding evolution under the "new mutations" or "mutation-limited" view that is now commonplace in molecular evolution. A new mutation arises and may "become established- we would say "become fixed" or "reach fixation" in population-genetics jargon- with a probability (not a certainty) that depends on its effects. If its effects are injurious, is has practically no chance of being established, and so on.

Morgan's verbal description is remarkably accurate. Later, in the 1920s, Haldane, Wright, and Fisher began to work out some approximations for the probability of fixation of a new mutant allele. For newly introduced neutral alleles,  (substitute 2N for diploids), where N is the population size, and this value is not affected by recessivity or dominance, just as Morgan says; for a newly introduced beneficial allele, , where s is the selective advantage; for a significantly deleterious allele, the probability of fixation is vanishingly small. Later, diffusion theory was used to derive a more general expression for the probability of fixation (e.g., Gillespie, 1998, p. 82)

where the starting frequency p would be 1/N for a new mutation in the haploid case (and 1/2N for the diploid case).

To the extent that there was a distinctive "mutationist" perspective on evolutionary genetics that was rejected for its non-Darwinian implications, this was it. While Haldane, Fisher and Wright worked out the theory₂ for the probability of fixation of a new mutation, they didn't use this knowledge for anything important, because evolution by new mutations was not part of their theory₁ of evolution. Instead, Morgan's view of evolution as a series of mutation-fixation events was rejected by the Modern Synthesis as the "lucky mutant" view, and was ignored for nearly 50 years; Kimura popularized a neutral version of this view, which remained associated with neutral evolution for another 30 years; and in the past 10 years, Morgan's perspective is emerging as a more general view that may serve as the basis for models of adaptation (e.g., Orr, 2002).

The Mendelian interpretation of continuous variation

The advocates of Darwin's view of blending inheritance and fluctuation fought hard against Mendelism early in the 20th century, leading to the infamous biometrician-Mendelian debate. Thus, a century ago, it was necessary to defend Mendelian principles from attack by those who- disparaging Mendelism's simplistic rules and suspecting its experimental foundations in "artificial" breeding- held out hopes for a fuzzier, more organic conception of heredity and variation that would fit better with Darwin's view. In Bateson's 1902 "defense" of Mendelism, he provides a Mendelian interpretation of continuous variation:

"In the case of a population presenting continuous variation in regard to say, stature, it is easy to see how purity of the gametes in respect of any intensities of that character might not in ordinary circumstances be capable of detection. There are doubtless more than two pure gametic forms of this character, but there may quite conceivably be six or eight. When it is remembered that each heterozygous combination of any two may have its own appropriate stature, and that such a character is distinctly dependent on external conditions, the mere fact that the observed curves of stature give 'chance distributions' is not surprising and may still be compatible with purity of gametes in respect of certain pure types." (p. 31)

By "chance distribution", Bateson is invoking what we now call a "normal distribution". Such a distribution "may still be compatible with the purity of the gametes", i.e., compatible with Mendelian inheritance, because it can result by the combined effects of a multiplicity of Mendelian loci (6 or 8, he imagines), each with 2 homozygotes and 1 heterozygote, with environmental variation due to "external conditions".

Thus, Bateson interpreted quantitative characters precisely as we do today, as the result of overlaying environmental fluctuation on a discrete distribution of genetic types. This interpretation is not due to little Ronny Fisher, the 12-year-old boy who would grow up to be a founder of mathematical population genetics and would declare that genetics was the key to Darwin's theory⁷, but to Bateson and other geneticists, including Danish botanist Wilhelm Johannsen and the Swedish geneticist Herman Nilsson-Ehle.

The Mendelian interpretation was bolstered by a series of precise quantitative experiments conducted by Johannsen with the Princess bean. Johannsen isolated 19 stable self-fertilizing lines, each of which produced seeds with a different average weight. Planting any single variety would produce a smooth distribution of seed weights. Johannsen selected larger beans to plant a new generation, but this had no significant effect on the distribution of seed weights, proving that this newly arising variation was not heritable Darwinian fluctuation, but non-heritable somatic variation. Johannsen coined the terms "genotype" and "phenotype" to help explain this distinction.

By 1909, both Johannsen and Nilsson-Ehle had contrived to generate populations that, at the level of "genotype", were known mixtures of discrete Mendelian types, but which- at the level of "phenotype"- produced a nice smooth bell-shaped distribution. Johannsen's distributions of beans are reproduced in the figure below (right) from Morgan (1916; online source). 

The evolution of quantitative characters

Finally, the Mendelians developed a causal theory for the gradual change in a quantitative character due to selection that negotiated the phenotype-genotype distinction and was appropriately probabilistic.

In the Darwinian view based on fluctuation and blending of hereditary substances, the superficial appearance that the whole population has shifted continuously and homogeneously reflects the underlying reality that hereditary substances have shifted continuously and homogeneously.

The new Mendelian view differed in two respects. First, given the genotype-phenotype distinction, selection of a particular phenotypic range implicates hereditary factors indirectly and probabilistically. For instance, Punnett (1911) constructs a simplified example in which there are just 3 genetically defined types, A, B and C, with mean weights of 10, 12 and 14 grains (a "grain" is a unit of weight equal to 0.065 gram). "A seed that weighs 12 grains may belong to any of these three strains. It may be an average seed of B, or a rather large seed of A, or a rather small seed of C" (p. 162; online source):

"On this view we can understand why selection of the largest seed[s] raises the average weight in the next generation. We are picking out more of C and less of A and B, and as this process is repeated the proportion of C gradually increases and we get the appearance of selection acting on a continuously varying homogenous material and producing a permanent effect."

Second, as the Mendelians stressed repeatedly, the end result of this process is a not a new complement of hereditary factors, but a mixture of old components in new and different proportions. The hereditary factors are not changed by this process (as Darwin and his followers wrongly believed): only their proportions in the population are changed. Without new mutations, the new population would never transcend the genetic limits inherent in the original mix.

Homework

The popular view of history reflected in the Mutationism Myth is that our contemporary understanding of evolution began with Fisher, Haldane and Wright, not with Bateson, Morgan, Johannsen, Punnett and others. I see this as a whitewashed version of history, in which the contributions of the Mendelians have been erased.

But lets consider for a moment that, just as Darwin's followers did not give up on blending inheritance without a nasty fight that created lasting suspicions about geneticists, they are not likely to give up Synthesis Historiography⁸ without a nasty fight that will leave a stain on critics such as myself. So, how does one convincingly establish a point about influence or credit? How do we know whose views were influential and whose views were purged? Here are some examples of types of information that might be useful:

• A popular evolution education web site has a timeline listing important contributors to evolutionary thinking. The timeline has a gap of a whole generation between the late-19th-century neo-Darwinians (e.g., Weismann) and the early "Synthesis" architects. Kimura is not listed.
• Morgan published several books on evolution that went through multiple printings; the Boston Public Library includes his 1916 book in its list of 100 most influential books of the 20th century.
• The Oxford Encyclopedia of Evolution, which includes biographic entries, does not have an entry for any Mendelian except Morgan, whose evolutionary views are not discussed.

In what other ways might we establish objectively that certain scientists, and not others, receive credit for their work and get included in histories? How could you generate a large amount of data quickly? How could one show an unwarranted or extra-scientific bias for or against certain authors, i.e., excluding the alternative possibility that "the judgment of history" favoring one person over another reflects true scientific merit?

Conclusion

The Mutationism Myth suggests that our contemporary understanding of evolution did not emerge until Fisher, Haldane and Wright combined Darwin's principle of selection with Mendelian genetics; and that a generation was wasted while Mendelians developed a "doomed rival" to Darwin's great theory, in the form of a "mutationist" view that denied selection.

In fact, the Mendelians did not develop such a view. Instead, their interpretations paved the way for the Modern Synthesis and laid the foundations for our contemporary genetics-based understanding of evolution: they developed the Hardy-Weinberg model, interpreted quantitative trait evolution correctly, and even thought ahead to the "new mutations" perspective currently making inroads into evolutionary genetics.

Among the Mendelians, I also would count Nikolai Vavilov, the extraordinary Russian geneticist who started the first global seed bank (which persists today at the Vavilov Institute), leading expeditions that collected some 200,000 seeds. In 1922 he made a fascinating contribution to "mutationist" thinking, proposing parallel variations as a key component of parallel evolution. Vavilov was sent by the Soviets to a prison camp, where he died in 1943.

The Soviets purged Vavilov because of his opposition to Lysenkoism, the non-Mendelian theory of genetics with a Lamarckian theme of improvement-through-effort that fit nicely with Soviet ideology. Why were the contributions of Mendelians purged from our history, leaving the false impression of a generation-long gap in our intellectual history? Why don't we count Bateson, Morgan, Punnett, Johannsen, and others among the "founders" of modern evolutionary thinking? Possible answers to this question will emerge in part 4 of The Mutationism Myth, where we explore the non-Darwinian aspects of Mendelian thinking, and in part 5, where we consider the "Modern Synthesis" as a restoration of Darwinian orthodoxy.

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References

Batson, W., and E. R. Saunders. 1902. Experimental Studies in the Physiology of Heredity. Reports to the Evolution Committee. Royal Society. (Bateson%20saunders&pg=PP1#v=onepage&q&f=false">online source)

Bateson, W. 1902. Mendel's Principles of Heredity: A Defense. Cambridge University Press, Cambridge. (online source)

Bateson, W. 1909. Heredity and Variation in Modern Light. Pp. 85-101 in A. C. Seward, ed. Darwin and Modern Science: Essays in Commemoration of the Centenary of the Birgh of Charles Darwin and of the Fiftieth Anniversary of the publication of the Origin of Species. Cambridge, London.

Gillespie, J. H. 1998. Population Genetics: A Concise Guide. Johns Hopkins University Press, Baltimore, MD.

Morgan, T. H. 1932. The Scientific Basis of Evolution. W.W. Norton & Co., New York.

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

Punnett, R. C. 1911. Mendelism. MacMillan. http://www.archive.org/stream/mendelism00punn#page/172

Stephens, C. 2001. Selection, Drift, and the "Forces" of Evolution. Philosophy of Science 71:550-570.

Sturtevant, A. H. 1965. The Early Mendelians. Proceedings of the American Philosophical Society 109:199-208.

Vavilov, N. I. 1922. The Law of Homologous Series in Variation. J. Heredity 12:47-89.


Notes

¹ As quoted in part 1, mutationism is a source of "mirth" for Dawkins.

² The words "doomed rivals" are also from Dawkins. Back when I was a lad in school, my evolution professor- Dr. Kenneth Christiansen, who has been at Grinnell College for at least 45 years and is still there today- had a slightly gentler way of referring to alternative theories as the "also-rans".

³ Note that Morgan's choice of words leaves some wiggle room that some other kind of variability could be offered "in support of" Darwin's theory. A century ago, admiration for Darwin was nearly universal, as it is today. The meaning of Darwin's theory, and ownership of the "Darwin" brand, were contested by scientists. By 1950, the "Modern Synthesis" school had captured the Darwin brand and began to use it more aggressively than they had dared to do before. However, things might have turned out differently. De Vries labeled himself as a "Darwinian". Bateson and others sometimes cozied up to "Darwinism".

⁴ Sturtevant (1965) lists 22 Mendelians who published from 1900 to 1905, and notes that all but 5 were under 40 (the older exceptions are de Vries, Garrod, Johannson, Wilson and Lang).

⁵ "stability analysis" means finding the "attractors" or points of stability in a dynamic system.

⁶ Hardy reveled in the purity of mathematics and stated that he had no desire to do anything useful. He said that his most important discovery was Srinivasan Ramanujan, a largely self-taught Indian genius who had written to Hardy and others seeking a mentor- only Hardy recognized his genius.

⁷ Synthesis Historiography attributes the resolution of Darwinism and Mendelism to Fisher (1918). In reality, the problem that Fisher (1918) solved was how to derive Galton's law as a formal consequence of Mendelian principles. Either this is a red herring, or it suggests that as late as 1918, "Darwinism" still implied a rejection of Mendelism in favor of blending. Note that Galton himself lacked the ideological purism of his followers: he believed in discontinuous evolutionary changes and felt that this was a missing element in Darwin's theory.

⁸ "Synthesis Historiography" is Ron Amundson's term for the industry of writing versions of history in which the Modern Synthesis is presented as the manifest destiny of science, and Mayr, et al are the heroes, while their intellectual opponents are fools and knaves.

^*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_myth3 (Arlin Stoltzfus, ©2010)

Science Education and Teaching Controversy

I'm beginning to realize that there are (at least) two fundamentally different approaches to teaching science. One strategy, which I'll call the "fact-based" approach, concentrates on communicating facts about the natural world. The other approach, which I'll call the "methodological approach" concentrates on teaching students how to acquire knowledge.

In the fact-based approach to science education, the emphasis is on making sure that students have a sound knowledge of the basic principles of physics, chemistry, geology, and biology. Let's take the teaching of evolution as an example. If you follow this strategy then you will want your students to know about the main mechanisms of evolution and the known facts about the history of life. You will only teach things that are supported by scientific evidence. In order to pass the course, students must demonstrate that they have acquired, and understand, the facts.

The goal here is to send students out into the real world armed with an understanding of what science has learned. Hopefully they'll be able to use that knowledge of evolution to choose the "right" side in any controversy.

The methodological approach concentrates on teaching students how to acquire knowledge using the scientific method. This "method" is not the kindergarten version so often seen in schools but the more fundamental version that emphasizes evidence, skepticism, and rational thinking. The idea here is not only to teach facts—although that's important—but to teach why those facts should be accepted as true. Another major goal of this method is teaching critical thinking and the desired outcome is a group of graduates who will be able to apply the methodology to any problem they encounter in the future. This includes problems that don't fall into the traditional science fields of physics, chemistry, geology, and biology.

The fact-based approach tends to avoid any distractions that might confuse students about what is known and what isn't. Thus, Intelligent Design Creationism cannot be discussed in this type of curriculum because there's nothing factual about creationism. It's not part of science.

That restriction doesn't apply if you are trying to teach critical thinking because the most important part of your objective is teaching students how to argue and how to reason. In that approach, you actually want to encourage controversy and debate in the classroom because that's how you learn to distinguish between wheat and chaff, or science and pseudoscience.

I was prompted to think about these two different approaches by a recent issue of Science containing a number of articles about science education.¹ One of them is "Arguing to Learn in Science: The Role of Collaborative, Critical Discourse" by Jonathan Osborne [April 23, 2010: doi: 10.1126/science.1183944]. Here's the abstract ...

Argument and debate are common in science, yet they are virtually absent from science education. Recent research shows, however, that opportunities for students to engage in collaborative discourse and argumentation offer a means of enhancing student conceptual understanding and students’ skills and capabilities with scientific reasoning. As one of the hallmarks of the scientist is critical, rational skepticism, the lack of opportunities to develop the ability to reason and argue scientifically would appear to be a significant weakness in contemporary educational practice. In short, knowing what is wrong matters as much as knowing what is right. This paper presents a summary of the main features of this body of research and discusses its implications for the teaching and learning of science.

Clearly, this approach is consistent with bringing creationist ideas into the classroom in order to teach students why they are wrong. You will also want to bring up astrology and the ancient theory of demon possession if that helps make the point. You can't discuss every single controversy, but, at the very least, you should include the "active" ones—the ones students will encounter as soon as they step outside the classroom and watch FOX News or listen to their preacher on Sunday morning.

"Teaching the controversy" is good science if you adopt the methodological approach to science education but it's anathema if you adopt the fact-based approach.

Here's A.C. Grayling, a philosopher at Birkbeck College, University of London, and also a Fellow of St Anne's College, Oxford, giving his opinion on science education. Can you guess which approach he favors? Why isn't he aware of the "controversy" in science education? I wonder if he avoids all controversial topics in his philosophy classes?

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1. Thanks to Bruce Alberts who, as editor-in-chief, is trying to promote more emphasis on science education.

P.S. I don't want to discuss whether the methodological approach is possible in American schools. If you think that science teachers are too stupid to adopt this approach, or if you think that many of them are secret creationists, then that's an entirely different problem. It's a defeatist attitude to conclude that the quality of science teachers is so bad that science education can't be fixed. If you have bad science teachers then the first step is to replace them with good ones. The sooner the better.

Junk RNA or Imaginary RNA?

RNA is very popular these days. It seems as though new varieties of RNA are being discovered just about every month. There have been breathless reports claiming that almost all of our genome is transcribed and most of the this RNA has to be functional even though we don't yet know what the function is. The fervor with which some people advocate a paradigm shift in thinking about RNA approaches that of a cult follower [see Greg Laden Gets Suckered by John Mattick].

We've known for decades that there are many types of RNA besides messenger RNA (mRNA encodes proteins). Besides the standard ribosomal RNAs and transfer RNAs (tRNAs), there are a variety of small RNAs required for splicing and many other functions. There's no doubt that some of the new discoveries are important as well. This is especially true of small regulatory RNAs.

However, the idea that a huge proportion of our genome could be devoted to synthesizing functional RNAs does not fit with the data showing that most of our genome is junk [see Shoddy But Not "Junk"?]. That hasn't stopped RNA cultists from promoting experiments leading to the conclusion that almost all of our genome is transcribed.

Late to the Party

Several people have already written about this paper including Carl Zimmer and PZ Myers. There are also summaries in Nature News and PLoS Biology.That may change. A paper just published in PLoS Biology shows that the earlier work was prone to artifacts. Some of those RNAs may not even be there and others are present in tiny amounts.

The work was done by Harm van Bakel in Tim Hughes' lab, right here in Toronto. It's only a few floors, and a bridge, from where I'm sitting right now. The title of their paper tries to put a positive spin on the results: "Most 'Dark Matter' Transcripts Are Associated With Known Genes" [van Bakel et. al. (2010)]. Nobody's buying that spin. They all recognize that the important result is not that non-coding RNAs are mostly associated with genes but the fact that they are not found in the rest of the genome. In other words, most of our genome is not transcribed in spite of what was said in earlier papers.

Van Bekal compared two different types of analysis. The first, called "tiling arrays," is a technique where bulk RNA (cDNA, actually) is hybridized to a series of probes on a microchip. The probes are short pieces of DNA corresponding to genomic sequences spaced every few thousand base pairs along each chromosome. When some RNA fragment hybridizes to one of these probes you score that as a "hit." The earlier experiments used this technique and the results indicated that almost every probe could hybridize an RNA fragment. Thus, as you scanned the chip you saw that almost every spot recorded a "hit." The conclusion is that almost all of the genome is transcribed even though only 2% corresponds to known genes.

The second type of analysis is called RNA-Seq and it relies on direct sequencing of RNA fragments. Basically, you copy the RNA into DNA, selecting for small 200 bp fragments. Using new sequencing technology, you then determine the sequence of one (single end) or both ends (paired end) of this cDNA. You may only get 30 bp of good sequence information but that's sufficient to place the transcript on the known genome sequence. By collecting millions of sequence reads, you can determine what parts of the genome are transcribed and you can also determine the frequency of transcription. The technique is much more quantitative than tiling experiments.

Van Bekel et al. show that using RNA-Seq they detect very little transcription from the regions between genes. On the other hand, using tiling arrays they detect much more transcription from these regions. They conclude that the tiling arrays are producing spurious results—possibly due to cross-hybridization or possibly due to detection of very low abundance transcripts. In other words, the conclusion that most of our genome is transcribed may be an artifact of the method.

The parts of the genome that are presumed to be transcribed but for which there is no function is called "dark matter." Here's the important finding in the author's own words.

To investigate the extent and nature of transcriptional dark matter, we have analyzed a diverse set of human and mouse tissues and cell lines using tiling microarrays and RNA-Seq. A meta-analysis of single- and paired-end read RNA-Seq data reveals that the proportion of transcripts originating from intergenic and intronic regions is much lower than identified by whole-genome tiling arrays, which appear to suffer from high false-positive rates for transcripts expressed at low levels.

Many of us dismissed the earlier results as transcriptional noise or "junk RNA." We thought that much of the genome could be transcribed at a very low level but this was mostly due to accidental transcription from spurious promoters. This low level of "accidental" transcription is perfectly consistent with what we know about RNA polymerase and DNA binding proteins [What is a gene, post-ENCODE?, How RNA Polymerase Binds to DNA]. Although we might have suspected that some of the "transcription" was a true artifact, it was difficult to see how the papers could have failed to consider such a possibility. They had been through peer review and the reviewers seemed to be satisfied with the data and the interpretation.

That's gonna change. I suspect that from now on everybody is going to ignore the tiling array experiments and pretend they don't exist. Not only that, but in light of recent results, I suspect more and more scientists will announce that they never believed the earlier results in the first place. Too bad they never said that in print.

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van Bakel, H., Nislow, C., Blencowe, B. and Hughes, T. (2010) Most "Dark Matter" Transcripts Are Associated With Known Genes. PLoS Biology 8: e1000371 [doi:10.1371/journal.pbio.1000371]

Is God Dead?

 
I stumbled upon this while looking for something else. It's the cover from April 8, 1966. I remember it well. It didn't seem like such a big deal at the time. We all assumed the answer was "yes." Not a big deal in the '60s.

If I recall correctly, the inside article was about some dude named Friedrich Nietzsche. Weird name. Nobody cared. The cover said it all.

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The Essence of Christianity

Right now there's a conference going on in Oxford, United Kingdom—that hotbed of Christian apologetics (and Richard Dawkins). John Wilkins is there. One of the topics is defining religion [Ruminations in Oxford].

John's "ruminations" remind me of the ongoing debate over the conflict between science and religion. Everyone knows that the conflict exists but everyone has their own idea about how far it penetrates into religion. As you all know, various accommodationists are trying hard to wall off a protected area of religion that science cannot enter. That allows science and religion to co-exist peacefully.

In order to do this, the accommodationists have to define the essence of a religion. They agree that belief in a six thousand year old Earth conflicts with science but, according to them, that's not an essential belief in Christianity. The people who believe that sort of nonsense don't represent the serious "sophisticated" Christians (like the ones in theology at Oxford). So, what are the essential beliefs that don't conflict with the scientific way of acquiring knowledge?

Here's how Michael Ruse describes them in his latest book, Science and Spirituality: Making Room for Faith in the Age of Science (p. 182). I wonder how many of the people at the conference will agree with Ruse about the four items that are essential for Christians? I wonder how many of them agree with Ruse that none of these four conflict with the scientific way of thinking?

With an eye to the discussion of the previous chapters, I want to pick out four items or claims that are central to Christian belief—four items that the Christian takes on faith. If you do not believe in these, then you should not call yourself a Christian. First, that there is a God who is creator, "maker of heaven and earth." Second, we humans have duties, moral tasks here on earth, in the execution of which we are going to be judged. Hence, God stands behind morality. Third, Jesus Christ came to earth and suffered because we humans are special, we are worth the effort by God. The usual way of expressing this is to say that we are "made in the image of God." We have "souls." Fourth and finally, there is the promise of "life everlasting." We can go to heaven, what ever that means.

Let me spell out carefully what I see as the task in this and the next chapter. It is not to defend Christianity as a true or compelling belief system. I take it that you can enter these chapters as an agnostic or an atheist and depart in the same frame of mind. I do not want to dissuade people from Christianity, nor do I want to convince them of it. I want to explain in a fair manner what is meant by Christianity in terms of the four points introduced in the last paragraph. I also want to show that you could hold these, if you so wish, in the light of modern science—if you prefer, in the face of modern science. In other words, the Christian's claims are not refuted by modern science—or indeed threatened or made less probable by modern science.

Here's my quick take on the four items.

1. God the creator: It's possible to imagine a Deist God who starts off the known universe then goes off somewhere to watch perpetual reruns of The Lawrence Welk Show. (Where does he go?) This sort of God does not conflict directly with science, even if you define science as a way of knowing that requires evidence, skepticism, and rationality. It's an unnecessary God but a relatively harmless one compared to some others. Nobody I know believes in such a God, including Keith Ward, Ken Miller and Francis Collins.

2. God stands behind morality and He will judge us: There's no scientific evidence to support the notion that morality has anything to do with supernatural beings and plenty of evidence against it. There's no scientific evidence that you will be judged by anyone except other humans. This belief conflicts with science.

3. Jesus Christ is/was God: The idea that a supernatural being appeared on Earth in the form of a real human and lived among a group of primitive farmers in some obscure part of the world is not consistent with anything we know by applying scientific reasoning. It conflicts with science big time. So does the idea that we have something called a "soul" that no other animal possesses.

4. When you die you go to heaven: Totally inconsistent with a scientific way of thinking. In spite of several thousand years of tying, no evidence of heaven has ever been produced. Or hell, for that matter. There is nothing about this silly belief that's even remotely consistent with science.

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Visitors

 

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Clarity vs Obscurity

 
Richard Dawkins says, "There are people who are so in love with obscurity—a nice warm fuzzy feeling of obscurity and obscurantism—that, if you say something clearly, they feel threatened." See the video below.

For some reason this reminds me of a book I just read by Keith Ward called "The Big Questions in Science and Religion." Perhaps it's because of the blurb on the back cover that says,

Ward effortlessly flows from one fascinating insight to another about the often contentious relationship between diverse religious views and the new scientific knowledge. Writing with both passion and clarity, he masterfully converys the depth, the difficulty, and the importance of the greatest intellectual and existential questions of the modern age.

"Clarity"? Don't make me laugh. Keith Ward has never met an example of obscurantism that he doesn't embrace.

Ward is a colleague of Dawkins at Oxford. I wonder if Dawkins was thinking of him when he made his statement? Or, he may have been thinking of another colleague, Alister McGrath.

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[Hat Tip: Clarity - A very nice statement by Dawkins, at RichardDawkins.net.]

Correlations

 
It's fascinating how opposition to science correlates with other positions on various issues. There's a reason why we call them IDiots.

Canada is in the midst of a debate on abortion. Right now there are no laws in Canada that prohibit abortion. We are a pro-choice country.

The current Conservative government under King Harper wants to change that but they're going about it in a very underhanded way. The first step is to refuse funding to foreign aid programs that permit abortion. The second step seems to be to refuse federal funding to a number of women's groups that are pro-choice.

What has this got to do with correlations? Denyse O'Leary, that's what. Denyse is a well-known anti-science writer who support just about any cockamainy idea from Intelligent Design Creationists. Now she's weighed in on the abortion issue. Here's her open letter to the Prime Minister [Off topic: Advice to the government re abortion funding]. Judge for yourself whether her views on this issue are any more coherent than her anti-science views.

Mr. Prime Minister and excellent minister Bev Oda:

Please stand firm against the people who will get money from aborting babies in other countries, if you cave in.

This is for a number of non-religious reasons:

1. There is NO reason to believe abortion will even be voluntary. And what can we do if it isn't? It is better if we Canadians just do not fund it. (If people in other countries want to force women to be aborted, to meet grant-based population reduction quotas, we cannot stop them. But at least we had nothing to do with it, right? It's not like the cheque is stamped 'From a grateful CANADA'. Surely, there are some shames we cannot stoop to.)

2. Contrary to population whackos, most of the world is in steep demographic decline. This is bad news for business, pension plans, etc. Why add to the problem? Right now, YOUR government is advertising for healthy young workers from abroad. So we should kill their successors?

3. Abortion clinics are run by people who do not mind killing babies for a living. Even if you didn't agree that that is a problem, a number of other evils result, including: Teachers molest underage girls and ship them to clinics for discreet abortions, unbeknown to their parents. Abortion clinics may also function on the adoption black market. = Would you keep it for a while instead of killing it, if we get you some money?

4. No one should believe anything an abortion clinic operator says about not killing viable babies. If he really cared about stuff like that, he would not likely do what he does now. So you can assume, for practical purposes, it is unreliable.

5. Some babies may be sold for research that should never be done on a human being, but remember that they do not technically exist.

Stand firm! Most of the criticism I hear about your government comes from NOT standing up for traditional Canadian values. Most of the praise I hear is for doing so.

And REPEAL Section 13 and FIRE Jennifer Lynch. Quit fooling around about that too. People are really angry.

Traditional values and civil rights are important to the people who would re-elect you.

Did I mention that Denyse is a Roman Catholic? Do you think it's relevant?

I'm sure Stephen Harper will be so proud to have the support of an intellectual like Denyse O'Leary.

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Who Asked Katarin MacLeod to Review this Book

 
Katarin MacLeod reviews a new book on evolution—one that's intended to educate children who lack an understanding of science [Evolution (Biology)-Juvenile literature].

According to the short bio at the end of her review ...

Katarin MacLeod is an Assistant Professor in Science Education at St. Francis Xavier University in Antigonish, NS. Her areas of interest include physics educational research (PER), and the incorporation of science, technology, society and environment (STSE) outcomes into science courses at all levels to help students understand the relevancy of science, increase scientific literacy, and to promote citizenship.

Here's part of her review. You can judge for yourself whether she is competent to teach science education at St. Francis Xavier University.

Although the text is very good in describing the theory of Evolution, there are points in the book where the author makes comments that could imply that Evolution is more than a theory. For example, “…Charles Darwin revealed the solution to the mystery of evolution” (p. 7). He also makes the comment that Evolution is the most important idea in all of biology (p. 7). Such phrases may lead the reader into thinking that scientists completely understand the theory of Evolution which would be incorrect, else Evolution would be a principle or a law and not a theory. As well, it is a bit bold to claim that evolution is the most important idea in all of biology – biology is a huge field of study with other key discoveries.

Hint to Professor MacLeod. Before you review your next book on evolution you'd better brush up on the difference between a fact and a theory and learn that a theory can never become a law.

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[Hat Tip: Richard B. Hoppe at Panda's Thumb]

Shame on the Royal Ontario Museum

 
The Royal Ontario Museum (ROM) is sponsoring a lecture by Deepak Chopra. You can see for yourself on the ROM website: An Evening with Deepak Chopra.

Here's the blurb ...

An Evening with Deepak Chopra
Wednesday, June 23, 7:00 - 8:00 pm (Doors Open 6:00 pm)

Status: Registration Starts May 14!

Director's Signature Series
The Warrior Emperor and China's Terracotta Army

World renowned teacher, author and philosopher Deepak Chopra presents his latest concepts in the field of mind-body medicine bridging the technological miracles of the West with the wisdom of the East. He will show you how your highest vision of yourself can be turned into physical reality and discuss how you can become a living cell within the body of a living universe. You don't join the cosmic dance - you become the dance. Deepak will address the deeper meaning of our existence including: What is our true nature? What is the meaning and purpose of our existence? How can I transform myself? How can I make a better world? Deepak explains how the greatest spiritual secrets are tied up in this simple answer: You can't change the body without changing the self, and you can't change the self without bringing in the soul. He explains, "It's all one process, and it begins with knowing that your body exists to mirror who you are and who you want to be."

Deepak Chopra is the author of more than 56 books translated into over 35 languages, including numerous New York Times bestsellers in both the fiction and non-fiction categories. He is a fellow of the American College of Physicians, a member of the American Association of Clinical Endocrinologists, Adjunct Professor at Kellogg School of Management and Senior Scientist with The Gallup Organization. Time magazine heralds Deepak Chopra as one of the top 100 heroes and icons of the century and credits him as "the poet-prophet of alternative medicine." For more information visit: www.deepakchopra.com

Location: Convocation Hall, 31 King’s College Circle, University of Toronto

Cost: Price: Ground VIP: $175, Rise Area: $89, 1st Balcony: $69, 2nd Balcony: $49, Behind Stage: $25

Tickets are non-refundable.

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I Don't Have Time for This!

 

The banner headline on the front page of The Toronto Star says, "U of T cracks the code." You can read the newspaper article on their website: U of T team decodes secret messages of our genes. ("U of T" refers to the University of Toronto - our newspaper thinks we're the only "T" university in the entire world.)

The hyperbole is beyond disgusting.

The work comes from labs run by Brendan Frey and Ben Blencowe and it claims to have discovered the "splicing code" mediating alternative splicing (Barash et al., 2010). You'll have to read the paper yourself to see it the headlines are justified. It's clear that Nature thought it was important 'cause they hyped it on the front cover of this week's issue.

The frequency of alternative splicing is a genuine scientific controversy. We've known for 30 years that some genes are alternatively spliced to produce different protein products. The controversy is over what percentage of genes have genuine biologically relevant alternative splice variants and what percentage simply exhibit low levels of inappropriate splicing errors.

Personally, I think most of the predicted splice variants are impossible. The data must be detecting splicing errors [Two Examples of "Alternative Splicing"]. I'd be surprised if more than 5% of human genes are alternatively spliced in a biologically relevant manner.

Barash et al. (2010) disagree. They begin their paper with the common mantra of the true believers.

Transcripts from approximately 95% of multi-exon human genes are spliced in more than one way, and in most cases the resulting transcripts are variably expressed between different cell and tissue types. This process of alternative splicing shapes how genetic information controls numerous critical cellular processes, and it is estimated that 15% to 50% of human disease mutations affect splice site selection.

I don't object to scientists who hold points of view that are different than mine—even if they're wrong! What I object to is those scientists who promote their personal opinions in scientific papers without even acknowledging that there's a genuine scientific controversy. You have to look very carefully in this paper for any mention of the idea that a lot of alternative splicing could simply be due to mistakes in the splicing machinery. And if that's true, then the "splicing code" that they've "deciphered" is just a way of detecting when the machinery will make a mistake.

We've come to expect that science writers can be taken in by scientists who exaggerate the importance of their own work, so I'm not blaming the journalists at The Toronto Star and I'm not even blaming the person who wrote the University of Toronto press release [U of T researchers crack 'splicing code']. I'll even forgive the writers at Nature for failing to be skeptical [The code within the code] [Gene regulation: Breaking the second genetic code].

It's scientists who have to accept the blame for the way science is presented to the general public.

Frey compared his computer decoder to the German Enigma encryption device, which helped the Allies defeat the Nazis after it fell into their hands.

“Just like in the old cryptographic systems in World War II, you’d have the Enigma machine…which would take an instruction and encode it in a complicated set of symbols,” he said.

“Well, biology works the same way. It turns out to control genetic messaging it makes use of a complicated set of symbols that are hidden in DNA.”

Given the number of biological activities needed to grow and govern our bodies, scientists had believed humans must have 100,000 genes or more to direct those myriad functions.

But that genomic search of the 3 billion base pairs that make up the rungs of our twisting DNA ladders revealed a meagre 20,000 genes, about the same number as the lowly nematode worm boasts.

“The nematode has about 1,000 cells, and we have at least 1,000 different neuron (cells) in our brains alone,” said Benjamin Blencowe, a U of T biochemist and the study’s co-senior author.

To achieve this huge complexity, our genes must be monumental multi-taskers, with each one having the potential to do dozens or even hundreds of different things in different parts of the body.

And to be such adroit role switchers, each gene must have an immensely complex set of instructions – or a code – to tell them what to do in any of the different tissues they need to perform in.

I wish I had time to present a good review of the paper but I don't. Sorry.

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Barash, Y., Calarco, J.A., Gao, W., Qun Pan, Q., Wang, X., Shai, O., Benjamin J. Blencowe, and Frey, B.J. (2010) Deciphering the splicing code. Nature 465: 53–59. [doi:10.1038/nature09000] [Supplementary Information]

Blogging Ethics

 

As Canadian Cynic notes, this applies to bloggers as well. It would be unethical for me to mention on my blog that I'd like Apple to send me a free iPhone 3Gs and a free iPad.

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Richard Dawkins on the Nature of Scientific (and Religious) Controversy

 

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[Hat Tip: Friendly Atheist]

The Mutationism Myth, II. Revolution

This is the fourth 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.

Arlin is going to explain to you why everything you thought you knew about mutationism is wrong. You may even be a supporter of mutationism without even being aware of it!

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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 with The Mutationism Myth, part 1. Then, in Theory vs Theory, we took a brief detour to distinguish theory₁ (grand conjecture) from theory₂ (body of abstract principles). Today we are back to the Mutationism Myth and our goal is to probe its claim that the scientific community rejected Darwin's ideas on erroneous grounds.¹

The Mutationism Myth, II. Revolution

The Mutationism Myth is a story told in the literature of neo-Darwinism, regarding the impact of the (re)discovery of Mendelian genetics a century ago. In this story, the discoverers of genetics (characterized as laboratory-bound geeks) misinterpret their discovery, thinking it incompatible with natural selection; the false gospel of these "mutationists" brings on a dark period that lasts until the 1930s, when theoretical population geneticists prove that genetics is the missing key to Darwinism; Darwinism is restored, and there is peace and unity in the land.

In typical versions of the mutationism story that we reviewed in part 1, the Mendelians cast a spell on the scientific community, convincing it of a false belief that either

• Mendelian genetics is inconsistent with the concept of natural selection or
• selection is irrelevant because mutational jumps alone explain evolution

For instance, Eldredge (2001) writes:

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

As noted earlier, a myth is not necessarily false. Some parts of the Mutationism Myth reflect history accurately, and others do not. An underlying truth in the Mutationism Myth is that, as a direct result of the re-discovery of Mendelian genetics, leading geneticists— Bateson, Johannsen, de Vries, Morgan, Punnett, and others— rejected Darwin's theory for how evolution works.

Our goal is to understand why. We must begin with heredity, the heart of the issue.

Re-discovering a lost theory

The re-discovery of Mendel's principles of heredity was nothing short of a revolution, and if you were trained in 19th-century views of heredity, this would be obvious, and there would be no need for me to explain it.

Unfortunately, the chances are good that you, dear reader, have been trained in the principles of Mendelism, and that puts us at a disadvantage. Once we can imagine the purity of hereditary factors, and we learn Johannsen's genotype-phenotype distinction, these principles seem to change our view of the world irreversibly, and its hard to understand what came before. Johannsen's quantitative-genetics experiments on seed weights of the Princess bean, conducted in the first decade of the 20th century, appear to have had more impact on evolutionary thinking than any single study conducted before or since. In the figure below, Johanssen (1903) shows the distribution of weights of beans from a plot planted with a mixture of seeds from pure self-fertilizing lines (the legend says "The variation of the weight of 5494 beans from the 1902 harvest, descendants of all weight classes in 1901") (online source):

The beans from the mixed plot show a nice bell-shaped distribution (figure). Similarly, the beans harvested from pure lines grown in separate garden plots also show nice bell-shaped distributions, though the means differ for each pure line. The key difference is in the results of selective breeding for heavier (or lighter) beans, i.e., planting a new crop using only the heaviest (or lightest) beans: selection shifts the distribution of seed weights in the mixed plot, but has no significant effect on the distribution of seed weights produced by a pure line.

Within just a few decades, neo-Darwinians such as Ford (1938) dismissed Johannsen's results as a logical necessity, as though the experiments proved nothing. Johannsen's studies had changed our understanding so profoundly that Ford was unable to imagine how scientists (mis)understood the world before.

I won't ask you to do what Ford could not, which is to forget genetics.

Instead, I would like to ask you to join me in imagining a different world— one in which particulate inheritance of pure hereditary factors does not apply.

We have been sent to this alien world as evolutionary experts, to consult with its scientists about how evolution might work on their planet. The alien scientists explain that, in their world, the bodies of organisms have differentiated organs composed of diverse cell-like units (CLUs), which swell, fuse, split and exchange material. The CLUs don't seem to have nuclei or central control centers. Instead, they are composed of substances that interact productively and grow, crystal-like (possibly some kind of prion-like protein, we think to ourselves). Different CLUs have different compositions, and thus have different developmental tendencies, e.g., some CLUs have a tendency to aggregate and interact to form a differentiated organ.

We are skeptical of the alleged lack of nuclei, so we explain the "nucleus" concept to the aliens and propose that CLUs actually have a spatially localized store of information that controls growth and development. The aliens listen carefully and ask clarifying questions in order to understand our hypothesis. Then they tell us that they know we are wrong. Alien scientists long ago developed a method of splitting CLUs which showed that the separated parts of CLUs largely retain their potential for growth and development, even if the CLUs are cut in multiple pieces. Thus, the alien scientists had demonstrated that CLUs and their substances have a hereditary aspect, but the potential for heredity seems to be dispersed in the substances, not centralized in a nucleus.

During the life of an organ, CLUs may come and go. CLUs circulating in the body are harvested continually in the reproductive organs, where substances are extracted to form minute reproductive corpuscles, RCs, whose role in reproduction is similar to gametes. However, the RCs or reproductive corpuscles don't have the 1-copy-of-each-factor neatness of earthly Mendelian gametes. The growable substances in the RCs are variable in amount, thus RCs vary in hereditary potencies. Furthermore, the composition of CLUs circulating in the body reflects the totality of what is happening in the body: because the body is continually growing and reacting and changing, the RCs are changing, too. In particular, the composition of the RCs tends to deviate more strongly when the organisms are stressed or face unusual conditions.

While some of the alien organisms are asexual, others have tri-parental reproduction that involves mixing of RCs from different parents. Each of the 3 parents makes a contribution of RCs, typically equal in size, though in some species, one type of parent contributes much more than the other two. When the parental RCs come together, the substances in them seem to mix or blend.

A different kind of evolution

The alien scientists have outlined the basis of heredity on their planet, and they are looking to us expectantly for ideas about how evolution is going to work. We were hoping to gather more facts, and particularly to hear from other experts about the diversity of life, and so on, but the aliens are eager for our ideas right away. What can we infer about evolution in a bottom-up manner, from an understanding of heredity?

We see immediately that it will be possible to apply some concept of "selection" in this world, but its going to be awfully slippery. We reach into our conceptual toolbox, and the first thing we find is the concept of "selection coefficient". But thats not useful on the alien planet, because there is no stable genetic entity to which one may apply the selection coefficient— everything in the alien world with a bearing on heredity seems to be variable in potency and to be subject to blending. Heredity depends on the differential growth of continuous substances, modulated by their differential incorporation into RCs due to conditions of life, and so on. The alien world lacks the algebraic neatness of pairwise combinations and pure factors.

In fact, our hearts sink as we realize that, because of this blending-together, it might be impossible for evolution to start from a single hereditary variant, as would be possible on earth starting with a single Mendelian mutant. The distinctive features of the individual variant would simply diffuse and blend.

But our discouragement is only temporarily. Yes, it would have been simple and easy if hereditary factors emerged discretely, combined in simple ratios, and maintained their purity during reproduction— but who said science was supposed to be simple and easy?

We are undaunted. We are determined to discover some way to apply the principle of selection. In fact, given that the RCs deviate more strongly under unusual conditions, we note with enthusiasm that extra hereditary variation will emerge just when it would be helpful to provide fuel for adaptation to new conditions! Due to hereditary blending, one variant individual, with a variation in a favorable direction, would not be enough.

But thats not a problem. In fact, to treat it as a "problem" is wrong-headed, because this alien world is not a world of discrete heredity anyway! Instead, on the alien planet, heredity is a bulk process, like the flow and mixing of liquids. The hereditary substances flow (metaphorically) in new directions every generation, and selection can get some leverage from these fluctuations of hereditary potency, even if there is not any single discrete particle to grasp. Selection would guide these fluctuations, building them smoothly from generation to generation. Possibly we could develop a mathematical formalism for this process by adapting the breeder's equation of quantitative genetics, although the shifting of hereditary potencies from one generation to the next would be problematic. An even more radical thought occurs to us: Lamarckian evolution can't happen in our world, but in the alien world, it just might be possible due to the way the RCs reflect what is going on in the body as it experiences its environment.

If you have followed me thus far, congratulations! You are one of the re-discoverers of Darwin's lost theory of evolution!

Evolution without mutation

Sadly, when I refer to a "lost theory", its not a joke, because Darwin's "Natural Selection Theory" (not to be confused with the principle of natural selection²) is largely unknown to contemporary scientists. During the Darwin bicentennial last year, I lost track of how many times "Darwin's theory" was explained by reference to "selection and random mutation" or some such anachronism.

Darwin had no such theory. Given Darwin's assumptions that inheritance is blending (not particulate), that the germ-line is responsive to external conditions (not isolated), and that hereditary potencies shift gradually every generation (not rarely and abruptly, from one pure, stable state to another), it is physically impossible for a rare trait, having arisen by some process, and conferring a fitness advantage of (for example) 2 %, to be passed on to offspring by a stable non-blended hereditary factor, thus conferring on the offspring a 2 % advantage, and for such a process to continue for thousands of generations until the previously rare trait prevails. We may think of evolution in this way: Darwin did not.

Instead, Darwinism 1.0 (Darwin's conception of evolution) is an automatic process of adjustment to altered conditions, dependent on a rampant process of "fluctuation" yielding abundant "infinitesimally small inherited modifications" in response to the effect of altered "conditions of life" on the "sexual organs" (Chs. 1, 2, 4 and 5 of Darwin 1859). Fluctuation was not rare and discrete, but shifted hereditary factors continuously and cumulatively each generation, producing visible effects in "several generations" (Ch. 1 of Darwin 1859). Muller (1956) referred to Darwinian fluctuation as "creeping variation". I have called it "variation on demand", and I also think that, to understand Darwin's view, its helpful to think of heredity and variation as processes mediated by fluids (liquids or gases). Darwin's critics, and quite a few of his friends such as Huxley and Galton, believed that individual "sports" (mutants) could be the start of something new in evolution, but this was not part of Darwin's theory, which invoked blending inheritance and held fast to natura non facit salta.

For those who would like to get more of a flavor of Darwin's view from his own writings, I have included a few passages below in an appendix. Readers may wish to go further by browsing online sources via the links provided. Others may wish to take a colorful look at Darwin's laws of variation from the Virtual Museum of the Origin of Species.

To account for his principles or "laws"³ of variation, Darwin proposed a "gemmule" theory for the mechanism of heredity, where "gemmules" are somewhat like the RCs or "reproductive corpuscles" in the fictional alien world described above.

Although Darwin's "Natural Selection" theory invoked Lamarckian effects, the fluctuation-selection process that Darwin called "Natural Selection" was recognized immediately as its mechanistic core. Only this core mechanism remains in the reformed view of Weismann and Wallace— "Darwinism 1.2" for our purposes—, which expunged Lamarckism and relied on selection of ever-present fluctuations, a process understood (in Darwinism 1.2) as the exclusive and all-powerful driving force of evolution.

Developing a new view of evolution

In fact, the "Mendelians" did not reject the principle of selection. Instead, they rejected "fluctuation" as the basis of evolutionary change for exactly the reason we would expect, namely that these fluctuations are not heritable. Johannsen's experiments were influential because they suggested that the fluctuations that emerge reliably every generation, i.e., Darwin's "endless slight peculiarities which distinguish the individuals of the same species and which cannot be accounted for by inheritance from either parent or from some more remote ancestor", are non-heritable and cannot be the basis for evolution by natural selection.

This is precisely the reason that geneticists gave, explicitly, for rejecting Darwin's view. For instance, in his 1911 book Mendelism, Punnett (of the "Punnett square" one studies in Genetics 101) explains the new "basis of evolution":

"The distinction between these two kinds of variation, so entirely different in their causation, renders it possible to obtain a clearer view of the process of evolution than that recently prevalent. . . Evolution only comes about throught the survival of certain variations and the elimination of others. But to be of any moment in evolutionary change a variation must be inherited. And to be inherited it must be represented in the gametes. This, as we have seen, is the case for those variations which we have termed mutations. For the inheritance of fluctuations, on the other hand, of the variations which result from the direct action of the environment upon the individual, there is no indisputable evidence. Consequently we have no reason for regarding them as playing any part in the production of that succession of temporarily stable forms which we term evolution. In the light of our present knowledge we must regard the mutation as the basis of evolution— as the material upon which natural selection works. For it is the only form of variation of whose heredity we have any certain knowledge.

It is evident that this view of the process of evolution is in some respects at variance with that generally held during the past half century. " (Punnett, 1911, p. 139-140; online source)

Punnett rejects "fluctuations", defined as "the variations which result from the direct action of the environment upon the individual".

It wasn't about rejecting natural selection: Punnett identifies mutation as the "basis" of evolution precisely on the grounds that it provides "the material on which selection works". While TH Morgan (1916) often avoided the phrase "natural selection", as in the following passage, he clearly is not rejecting a role for differential effects of fitness

"evolution has taken place by the incorporation into the race of those mutations that are beneficial to the life and reproduction of the organism" (p. 194) (online source)

This "mutationist" view was merely the start of a new way of looking at evolution. In the next installment, we'll find out what sort of understanding of evolution emerged among this new generation of evolutionists inspired by Mendelian principles. We'll see that, contrary to the Mutationism Myth, the period between the discovery of genetics and the origin of the Modern Synthesis in the 1930s was not a dark period of confusion at all, but a period of innovation that gave rise to key elements of the genetics-based understanding of evolution that persists today, including new ways of understanding selection.

Looking ahead

This post raises several issues that will receive attention in future posts of The Curious Disconnect. For instance, the mutationists rejected "Natural Selection", the theory₁ of Darwin, but not the "concept of selection" (as mistakenly asserted by Eldredge, above). In a later post, we will explore how the ambiguity in "natural selection" covers a multitude of sins (e.g., Charlesworth, 2005), and we'll consider ways to speak (and think) more clearly.

A second issue is the cult of personality that has developed around Darwin, which instills in so many scientists the desire to align themselves with Darwin and label themselves "Darwinists" while ignoring Darwin's actual views. Rather than reject or defend Darwin's actual theory, the cultists make personal excuses for Darwin ("he couldn't have known!"), as though science were about judging persons rather than evaluating theories. In a future post, we'll explore the distorting influence of the Darwin Fetish.

A third issue has to do with the structure of Darwin's theory, and more generally, how we determine the structure of a theory, and how the parts fit together. This will become important when we evaluate the deeply problematic claim of the Modern Synthesis to have reconciled Darwin's view with genetics. In essence, the architects of the Modern Synthesis will claim that "the maintenance of abundant infinitesimal variation in the gene pool" replaces "fluctuation" while leaving the rest of Darwin's theory unchanged.

Summary

Darwin espoused a theory of evolution, not merely a principle of selection. If this theory merely asserted the principle of selection, then no possible finding in genetics could contradict it. In fact, Darwin's theory invoked the principle of selection, in the context of a mechanism he called "fluctuation", to account for most of the actual facts of evolution, leaving a residue to be explained by other means (Lamarckian and Buffonian effects)— other means that Darwin's followers soon rejected as untenable, leaving only the fluctuation-selection process.

Thus, prior to the discovery of genetics, Darwin's theory was understood correctly to rely on continuous hereditary variation that Darwin called "fluctuation", and that was induced by environmental conditions, not inherited from parents. The Mendelians argued that, if we wish to understand the "the basis of evolution— the material on which selection works", we must look to mutation, not to Darwin's "fluctuations", because variations induced by conditions are not heritable.

Little of this is understood today, because "Darwinism" or "Darwin's theory" has been redefined, and the original meaning of "Darwin's theory" has gone done the proverbial memory hole.

References

Charlesworth, B. 2005. On the Origins of Novelty and Variation. Science 310:1619-1620.

Darwin, C. 1859. On the Origin of Species. John Murray, London.

Darwin, C. 1883. Variation of Animals and Plants under Domestication. D. Appleton & Co., New York.

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

Ford, E. B. 1938. The Genetic Basis of Adaptation. Pp. 43-56 in G. R. de Beer, ed. Evolution. Clarendon Press, Oxford.

Johannsen, W. L. 1903. Erblichkeit in Populationen und in reinen Linien. Gustav Fischer, Jena.

Morgan, T. H. 1916. A Critique of the Theory of Evolution. Princeton University Press, Princeton, NJ.

Muller, H. J. 1956. On the Relation between Chromosome Changes and Gene Mutation. Brookhaven Symposia in Biology 8:126-147.

Punnett, R. C. 1911. Mendelism. MacMillan.

Appendix: Darwin's principles of heredity

Three passages below illustrate Darwin's view of the emergence of hereditary variation. The first indicates that the emergence of hereditary variation occurs on the scale of a few generations— no waiting around for mutations— and that the fluctuations build up cumulatively:

"It seems clear that organic beings must be exposed during several generations to new conditions to cause any great amount of variation; and that, when the organisation has once begun to vary, it generally continues varying for many generations." (Darwin, 1859, Ch. 1; online source

Darwin knew that "sports" (mutants) could have heritable effects, but he imagined that infinitesimal fluctuations were even more likely to be heritable:

"If strange and rare deviations of structure are really inherited, less strange and commoner deviations may be freely admitted to be heritable. Perhaps the correct way of viewing the whole subject would be, to look at the inheritance of every character whatever as the rule, and non-inheritance as the anomaly" (Darwin, 1859, Ch. 1; online source).

Darwin learned about heredity the hard way: by exchanging hand-written letters with hobbyists and stockmen who bred pigeons, sheep, dogs, and so on. Below he is describing an experiment in domestication of ducks from wild eggs, based on information provided by Mr. Hewitt, a source referenced by Darwin many times in his works:

"Mr. Hewitt found that his young birds always changed and deteriorated in character in the course of two or three generations; notwithstanding that great care was taken to prevent their crossing with tame ducks. After the third generation his birds lost the elegant carriage of the wild species, and began to acquire the gait of the common duck. They increased in size in each generation, and their legs became less fine. The white collar round the neck of the mallard became broader and less regular, and some of the longer primary wing-feathers became more or less white. When this occurred, Mr. Hewitt destroyed nearly the whole of his stock and procured fresh eggs from wild nests; so that he never bred the same family for more than five or six generations. His birds continued to pair together, and never became polygamous like the common domestic duck. I have given these details, because no other case, as far as I know, has been so carefully recorded by a competent observer of the progress of change in wild birds reared for several generations in a domestic condition. "(Darwin, 1883, p. 293; online source)

Thus, Darwin is describing subtle variations that emerge in response to new conditions, and that emerge immediately or, at least, within a few generations. He saw hereditary fluctuation as an effectively continuous process, i.e., a process that can be subdivided arbitrarily in time and in outcome because it is the summation of infinitesimal increments. Adaptation can happen rapidly and reliably because organisms start to vary immediately upon encountering new conditions. Similar variations will be manifested in many individuals (as in the case of the ducks above), so that multiple members of a "race" may emerge and interbreed simultaneously with, or prior to, selection. This avoids the problems posed by the swamping effect of blending inheritance (Darwin did not believe that a solitary variant could begin an evolutionary change). Darwin's principles of variation are roughly that

• hereditary variation emerges in response to "altered conditions of life" (e.g., domestication);
• the process is so rapid and productive that visible effects appear in one or a few generations;
• continuous ("infinitesimal", "insensible") fluctuations occur in virtually all characters;
• some effects are definite or reliable ("all or nearly all the offspring of individuals exposed to certain coditions during several generations are modified in the same manner"), while others are "indefinite" (isotropic);
• definite effects reflect mainly internal (developmental) causes, but also external (environmental) and Lamarckian causes ("effects of use and disuse").

Notes

¹ An updated version of this post will be available at http://www.molevol.org/cdblog/mutationism_myth2

² Don't blame me for this egregious ambiguity, which we will address in a future post.

³ Today we would call these laws "principles" or "generalizations". "Laws" in 19th century science are empirical generalizations, reached by the method of Baconian induction: collect lots of facts and distill them into generalizations.

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