Thursday, November 26, 2015


I'm creating a post where I can store quotations so I can link to them from other posts. Enjoy.
The great fear of many leading creationists and the misunderstanding of many creationist students is that accepting MN [methodological naturalism] rules for doing science will necesarily lead to a supernaturalless/Godless worldview.
Brian Alters (2005) p. 77

Persons in this faction [of theists] basically accept evolutionary theory with the proviso that the God of the Bible, not chance, decided the human outcome by directly guiding the process. Such theists are most commonly referred to as theistic evolutionists.
Brian Alters (2005) p. 62

Science reveals where religion conceals. Where religion purports to explain, it actually resorts to tautology. To assert that "God did it" is no more than an admission of ignorance dressed deceitfully as an explanation...
Peter Atkins

The defective design of organisms could be attributed to the gods of the ancient Greeks, Romans, and Egyptians, who fought with one another, made blunders, and were clumsy in their endeavors. But, in my view, it is not compatible with special action by the omniscient and omnipotent God of Judaism, Christianlity, and Islam.
Francisco J. Ayala (2004) p. 71

In conclusion, then, macroevolutionary processes are underlain by microevolutionary phenomena and are compatible with microevolutionary theories, but macroevolutionary studies require the formulation of autonomous hypotheses and models (which must be tested using macroevolutionary evidence). In this (epistemologically) very important sense, macroevolution is decoupled from microevolution: macroevolution is an autonomous field of evolutionary study.
Francisco J. Ayala (1983) p. 131

Science is not committed to the nonexistence of God, as it would be if it were based on metaphysical naturalism. Science is committed to naturalistic explanations. Science does not count any explanation that appeals to God or to supernatural phenomena as a scientific explanation (thus it is committed to methodological naturalism).
Lynn Rudder Baker (2000)

I once made the remark that two things disappeared in 1990: one was communism, the other was biochemistry and that only one of them should be allowed to come back.
Sydney Brenner (2000)

There will be no difficulty in computers being adapted to biology. There will be luddites. But they will be buried.
Sydney Brenner

One of the most frightening things in the Western world, and in this country in particular, is the number of people who believe in things that are scientifically false. If someone tells me that the earth is less than 10,000 years old, in my opinion he should see a psychiatrist.
Francis Crick

The Astonishing Hypothesis is that "You," your joys and your sorrows, your memories and your ambitions, your sense of personal identity and free will, are in fact no more than the behavior of a vast assembly of nerve cell and their associated molecules.
Francis Crick (1994)

My own view is that conclusions about the evolution of human behavior should be based on research at least as rigorous as that used in studying nonhuman animals. And if you read the animal behavior journals, you'll see that this requirement sets the bar pretty high, so that many assertions about evolutionary psychology sink without a trace.
Jerry Coyne (2009)

Although I am fully convinced of the truth of the views given in this volume, I by no means expect to convince experienced naturalists whose minds are stocked with a multitude of facts all viewed, during a long course of years, from a point of view directly opposite to mine. It is so easy to hide our ignorance under such expressions as "plan of creation," "unity of design," etc., and to think that we give an explanation when we only restate a fact. Any one whose disposition leads him to attach more weight to unexplained difficulties than to the explanation of a certain number of facts will certainly reject the theory.
Charles Darwin (1859)

The old argument of design in nature, as given by Paley, which formerly
seemed to me to be so conclusive, fails, now that the law of natural selection has been discovered. We can no longer argue that, for instance, the beautiful hinge of a bivalve shell must have been made by an intelligent being, like the hinge of a door by man. There seems to be no more design in the variability of organic beings and in the action of natural selection, than in the course which the wind blows.

Charles Darwin (c1880)

An atheist before Darwin could have said, following Hume: 'I have no explanation for complex biological design. All I know is that God isn't a good explanation, so we must wait and hope that somebody comes up with a better one.' I can't help feeling that such a position, though logically sound, would have left one feeling pretty unsatisfied, and that although atheism might have been logically tenable before Darwin, Darwin made it possible to be an intellectually fulfilled atheist.
Richard Dawkins

Theologians, if they want to remain honest, should make a choice. You can claim your own magisterium, separate from science's but still deserving of respect. But in that case you have to renounce miracles. Or, you can keep your Lourdes and your miracles ... But then you must kiss goodbye to separate magisteria and your high-minded aspiration to converge on science. The desire to have it both ways is not surprising in a good propagandist. What is surprising is the readiness of liberal agnostics to go along with it; and their readiness to write off, as simplistic, insensitive extremists, those of us with the temerity to blow the whistle.
Richard Dawkins (2003) p.150

It is absolutely safe to say that if you meet someone who claims not to believe in evolution, that person is ignorant, stupid or insane (or wicked, but I'd rather not consider that).
Richard Dawkins (1989)

... those evolutionists who see no conflict between evolution and their religious beliefs have been careful not to look as closely as we have been looking, or else hold a religious view that gives God what we might call a merely ceremonial role to play.
Daniel C. Dennett (1995) p.310

Operational science takes no position about the existence or non-existence of the supernatural; it only requires that this factor is not to be invoked in scientific explanations. Calling down special-purpose miracles as explanations constitutes a form of intellectual "cheating."
Richard E. Dickerson (1992) p.119

Seen in the light of evolution, biology is, perhaps, intellectually the most satisfying and inspiring science. Without that light it becomes a pile of sundry facts—some of them interesting or curious but making no meaningful picture as a whole.
Theodosius Dobbzhansky (Dobzhansky 1973)

It is wrong to hold creation and evolution as mutually exclusive alternatives. I am a creationist and an evolutionist. Evolution is God's, or Nature's method of creation. Creation is not an event that happened in 4004 BC; it is a process that began some 10 billion years ago and is still under way.
Theodosius Dobbzhansky (Dobzhansky 1973)

Under the conditions described [for Hardy-Weinberg equilibrium], there is a genetic inertia in mendelian populations. Unless mutation, selection, differential migration, certain changes in the mating pattern, or a drop in population size disturbs the equilibrium, there is no change in the genetic structure of the population. To a very large degree, overcoming this inertia (especially changing of the gene frequency) is what is described as "evolution."
Paul R. Ehrlich and Richard W. Holm (1963) p.95

Speciation is critical to conserving the results of both natural selection and genetic drift. Speciation is obviously central to the fate of genetic variation, and a major shaper of patterns of evolutionary change through evolutionary time. It is as if Darwinians—neo- and ulra- most certainly included—care only for the process generating change, and not about its ultimate fate in geological time.
Niles Eldredge (1995) p.106

Macroevolution is more than repeated rounds of microevolution.
Douglas H. Erwin (2000)

Just as mutation and drift introduce a strong random component into the process of adaptation, mass extinctions introduce chance into the process of diversification. This is because mass extinctions are a sampling process analogous to genetic drift. Instead of sampling allele frequenceis, mass extinctions samples species and lineages. ... The punchline? Chance plays a large role in the processes responsible for adaptation and diversity.
Freeman and Herron (1998) p.520

It is naïve to think that if a species' environment changes the species must adapt or else become extinct.... Just as a changed environment need not set in motion selection for new adaptations, new adaptations may evolve in an unchanging environment if new mutations arise that are superior to any pre-existing variations.
Douglas Futuyma

There is no justification for teaching creationism in the science classroom. But if it were taught, would it be subjected to the same critical analysis as the creationists insist should be brought to bear on evolution?
Douglas J. Futuyma (1982) p.217

I have championed contingency, and will continue to do so, because its large realm and legitimate claims have been so poorly attended by evolutionary scientists who cannot discern the beat of this different drummer while their brains and ears remain tuned to only the sounds of general theory.
Stephen Jay Gould (2002) p. 1339

The essence of Darwinism lies in its claim that natural selection creates the fit. Variation is ubiquitous and random in direction. It supplies raw material only. Natural selection directs the course of evolutionary change.
Stephen Jay Gould (1980)

Progress is a noxious, culturally embedded, untestable, nonoperational, intractable idea that must be replaced if we wish to understand the patterns of history.
Stephen Jay Gould (1988)

The shift of gene frequencies in local populations is an adequate model for all evolutionary processes—or so the current orthodoxy states.
Stephen Jay Gould (1980) p. 187

Rudyard Kipling asked how the leopard got its spots, the rhino its wrinkled skin. He called his answers "just-so stories." When evolutionists try to explain form and behavior, they also tell just-so stories—and the agent is natural selection. Virtuosity in invention replaces testability as the criterion for acceptance.
Stephen Jay Gould (1980)

Since 'change of gene frequencies in populations' is the 'official' definition of evolution, randomness has transgressed Darwin's border and asserted itself as an agent of evolutionary change.
Stephen Jay Gould (1983) p. 335

The first commandment for all versions of NOMA might be summarized by stating: "Thou shalt not mix the magisteria by claiming that God directly ordains important events in the history of nature by special interference knowable only through revelation and not accessible to science." In common parlance, we refer to such special interference as "miracle"—operationally defined as a unique and temporary suspension of natural law to reorder the facts of nature by divine fiat.
Stephen Jay Gould (1999) p. 84

[My diagram] accepts the Darwinian contention that microevolutionary modes and principles can build grand patterns by cumulation through geological immensity, but rejects the argument that such extrapolations can render the entire panoply of phenomena in life's history without adding explicitly macroevolutionary modes for distinctive expression of these processes at higher tiers of time ...
Stephen Jay Gould (2002) p. 21

The world is not inhabited exclusively by fools, and when a subject arouses intense interest, as this one has, something other than semantics is usually at stake.
Stephen Jay Gould (1982)

We wish to question a deeply engrained habit of thinking among students of evolution. We call it the adaptationist programme, or the Panglossian paradigm.
S.J. Gould & R.C. Lewontin (1979) p. 584

We welcome the richness that a pluralist approach, so akin to Darwin's spirit, can provide.
S.J. Gould & R.C. Lewontin (1979) p. 584

My practise as a scientist is atheistic. That is to say, when I set up an experiment I assume that no god, angel, or devil is going to interfere with its course; and this assumption has been justified by such success as I have achieved in my professional career. I should therefore be intellectually dishonest if I were not also atheistic in the affairs of the world. And I should be a coward if I did not state my theoretical views in public.
J.B.S. Haldane

Since religion ... stands or falls with the question of cosmic purpose, the Darwinian debunking of design—and with it the apparent undoing of cosmic teleology as well—strikes right at the heart of the most prized religious intuition of humans, now and always.
John F. Haught (2004) p. 230

Whatever the God implied by evolutionary theory may be like, He is not the Protestant God of waste not, want not. He is also not a loving God who cares about his productions. He is not even the awful God portrayed in the book of Job. The God of the Galapagos is careless, wasteful, indifferent, almost diabolical. He is certainly not the sort of God to whom anyone would be inclined to pray.
David I. Hull (1991) p. 486

Johnson finds the commitment of scientists to totally naturalistic explanations dogmatic and close-minded, but scientists have no choice. Once they allow reference to God or miraculous forces to explain the first origin of life or the evoluton of the human species, they have no way of limiting this sort of explanation.
David I. Hull (1991) p. 486

This evolutionary procedure —the formation of a dominant neocortex coupled with the persistence of a nervous and hormonal system partially, but not totally, under the rule of the neocortex—strongly resembles the tinkerer's procedure. It is somewhat like adding a jet engine to an old horse cart. It is not surprising ... that accidents, difficulties, and conflicts can occur.
François Jacob (1977) p.1166
Jacob, F. (1977) Evolution and Tinkering Sci. 196:1161-1166.

Natural selection has no analogy with any aspect of human behavior. However, if one wanted to play with a comparison, one would have to say that natural selection does not work as an engineer works. It works like a tinkerer—a tinkerer who does not know exactly what he is going to produce but uses whatever he finds around him whether it be pieces of string, fragments of wood, or old cardboards; in short it works like a tinkerer who uses everything at his disposal to produce some kind of workable object.
François Jacob (1977) p.1163

It is hard to realize that the living world as we know it is just one among many possibilities; that its actual structure results from the history of the earth. Yet living organisms are historical structures: literally creations of history. They represent, not a perfect product of engineering, but a patchwork of odd sets pieced together when and where opportunities arose. For the opportunism of natural selection is not simply a matter of indifference to the structure and operation of its products. It reflects the very nature of a historical process full of contingency.
François Jacob (1977) p.1166

Ecologists and microevolutionists are beginning to appreciate the importance of events over larger time scales than the decades or centuries that are their usual bounds, and a new effort is needed from both neontological and paleontological sides to get beyond a simple extrapolation of ecological phenomena into macroevolutionary time scales.
Jablonski, D. et al (1997)

Many biochemists find it easy to accept the concept that large portions of protein molecules serve mainly to bring the molecule up to suitable size and shape and have very little specific function as compared with small specialized active sites. Most of a protein molecule, according to this concept, can evolve freely by random drift
Thomas H. Jukes (1980) p.204

In conclusion, I would like to emphasize the importance of random genetic drift as a major cause of evolution. We must be liberated, so to speak, from the selective constraint posed by the neo-Darwinian (or the synthetic) theory of evolution.
Motoo Kimura (1991)

In contrast to the Darwinian theory of evolution by natural selection, the neutral theory emphasizes the great importance of random genetic drift (due to finite population size) and mutation pressure as the main causes of molecular evolution.
Mootoo Kimura (1991)

According to the neutral mutation–random drift hypothesis of molecular evolution and polymorphism1,2, most mutant substitutions detected through comparative studies of homologous proteins (and the nucleotide sequences) are the results of random fixation of selectively neutral or nearly neutral mutations. This is in sharp contrast to the orthodox neo-Darwinian view that practically all mutant substitutions occurring within species in the course of evolution are caused by positive Darwinian selection.
Mootoo Kimura (1977)

Calculating the rate of evolution in terms of nucleotide substitutions seems to give a value so
high that many of the mutations involved must be neutral ones

Mootoo Kimura 1968

Selective elimination of definitely deleterious mutants and random fixation of selectively neutral or very slightly deleterious mutants occur far more frequently in evolution than positive Darwinian selection of definitely advantageous mutants.
Mootoo Kimura and Tomoko Ohta (1974)

The main tenet of the neutral theory is that the great majority of evolutionary changes at the molecular level are caused not by Darwinian selection but by random fixation of selectively neutral (or very nearly neutral) alleles through random sampling drift under continued mutation pressure.
Mootoo Kimura (1989)

There appears to be considerable latitude at the molecular level for random genetic changes that have no effect upon the fitness of the organism. Selectively neutral mutations, if they occur, become passively fixed as evolutionary changes through the action of random genetic drift.
J.L King and T.H. Jukes (1969) p.789

The idea of selectively neutral change at the molecular level has not been readily accepted by many classical evolutionists, perhaps because of the pervassiveness of Darwinian thought.
J.L King and T.H. Jukes (1969) p.788

The suggestion that macroevolution should be divorced from microevolution provides Creationists only with a debating point. It allows Creationists to say that there are some evolutonary theorists who distinguish the mechanisms studied in classical population genetics from those they take to be involved in large-scale evolutionary change ... But this is not to suppose that the distinction drawn by heterodox evolutionists is that favored by the Creationists.
Philip Kitcher (1982) p.150

Overheard at breakfast on the final day of a recent scientific meeting: "Do you believe in macroevolution?" Came the reply: "Well, it depends on how you define it.".
Roger Lewin (1980) p.884.

The central question of the Chicago conference was whether the mechanisms underlying microevolution can be extrapolated to explain the phenomena of macroevolution. At the risk of doing violence to the positions of some of the people at the meeting, the answer can be given as a clear, No.
Roger Lewin (1980) p.884.

The fact is that almost the entire theoretical apparatus of random genetic drift and directional selection can be derived from a haploid model of the genome and that the introduction of diploidy and sexual recombination makes no qualitative chane and only trivial quantitative changes in the predictions of evolution under these forces.
Richard C. Lewontin (1974) p.83

The [neoclassical] theory does not deny adaptive evolution but only that the vast quantity of molecular variation within populations and, consequently, much of the molecular evolution among species, has anything to do with that adaptive process
Richard C. Lewontin (1974) p.85

The false view of evolution as a process of global optimizing has been applied literally by engineers who, taken in by a mistaken metaphor, have attempted to find globally optimal solutions to design problems by writing programs that model evolution by natural selection.
Richard Lewontin

Evolution is a process of change in the genetic makeup of populations, with the most basic component being change in allele frequencies with time.
Wen-Hsiung Li (1997) p.35

... the independence of macroevolution is affirmed not only by species selection but also by other processes such as effect sorting among species.
Bruce S. Lieberman and Elisabeth S. Vrba (2005)

Macroevolution is given expanded meaning by punctuated equilibrium, which is a theory more about species and their reality and individuality (sensu Hull 1980) than about speciation.
Bruce S. Lieberman and Elisabeth S. Vrba (2005)

The universe doesn't seem to me to be like the kind of entity that could have a higher purpose. I literally don't know what it would mean to say that the universe has a higher purpose. But I also have to say just simply as far as my own personal experience is concerned I have not found it a depressing doctrine. I do not find myself in the least depressed by feeling that if there is a purpose it's a purpose in my friends in my people I love and myself and human beings. It's a product of human beings it's not something that's sort of you know comes out the physical universe because the universe was created.
John Maynard Smith (1998)

Molecular genetics has found that mutations frequently occur in which the new allele produces no change in the fitness of the phenotype. Kimura (1983) has called the occurrence of such mutations neutral evolution, and others have referred to it as non-Darwinian evolution. Both terms are misleading. Evolution involves the fitness of individuals and populations, not of genes. When a genotype, favored by selection, carries along as hitchhikers a few newly arisen and strictly neutral alleles, it has no influence on evolution. This may be called evolutionary 'noise' but it is not evolution. However, Kimura is correct in pointing out that much of the molecular variation of the genotype is due to neutral mutations. Having no effect on the phenotype, they are immune to selection.
Ernst Mayr (2001) p.199

... I pointed out more than a decade ago (1977) that 'the reductionist explanation, so widely adopted in recent decades— Evolution is a change in gene frequencies in populations—is not only not explanatory, but is in fact misleading. Far more revealing is the definition: 'Evolution is change in the adaptation *and* in the diversity of populations of organisms.'
Ernst Mayr (2001) p.162

Neither the discovery of numerous new facts relating to evolution nor the development of new concepts of speciation and genetic variation have required any essential revision of the picture of evolution as developed during the evolutionary synthesis. I emphatically deny the claims of various authors that these recent developments have led to an end of Darwinism, or of neo-Darwinism, or of the evolutionary synthesis.
Ernst Mayr (1988) p.191

The attack directed by Gould and Lewontin against unsupported adaptationist explanations in the literature is fully justified. But the most absurd among these claims were made several generations ago, not by modern evolutionists.
Ernst Mayr (1988) p.152

[referring to Tielhard de Chardin] ... it's author can be accused of dishonesty only on the grounds that before deceiving others he has taken great pains to deceive himself.
Peter Medawar (1961) p.1

Although not completely random, chance does affect which mutations, which mistakes, appear in which individuals. ... this inherent unpredictability is not a matter of inadequate scientific knowledge. Rather, it is a reflection that the behavior of matter itself is indeterminate, and therefore unpredictable. It is one of the reasons why we cannot predict, with any detailed certainty, the future path of evolution.
Kenneth R. Miller (1999) p. 233

... evolution is as much a fact as anything we know in science. It is a fact that we humans did not appear suddenly on this planet, de novo creations without ancestors, and it is a fact that the threads of ancestry are clear for us and for hundreds of other species and groups.
Kenneth R. Miller (1999) p. 233

No question about it. Rewind that tape, let it run again, and events might come out differently at every turn. Surely this means that mankind's appearance on this planet was not preordained, that we are here not as the products of an inevitable procession of evolutionary success, but as an afterthought, a minor detail, a happenstance in a history that might just as well have left us out. I agree.
Kenneth R. Miller (1999) p. 233

In any discussion of the question of "Intelligent Design," it is absolutely essential to determine what is meant by the term itself. If, for example, the advocates of design wish to suggest that the intricacies of nature, life, and the universe reveal a world of meaning and purpose consistent with an overarching, possibly Divine, intelligence, then their point is philosophical, not scientific. It is a philosophical point of view, incidentally, that I share, along with many scientists.
Kenneth R. Miller (2004) p. 94

The thesis I shall present in this book is that the biosphere does not contain a predictable class of objects or of events but constitutes a particular occurrence, compatible indeed with first principles, but not deducible from those principles and therefore essentially unpredictable.
Jacques Monod (1971) p.43

All religions, nearly all philosophies, and even a part of science testify to the unwearying, heroic effort of mankind desperately denying its own contingency."
Jacques Monod (1971) p.44

Another curious aspect of the theory of evolution is that everybody thinks he understands it. I mean philosophers, social scientists, and so on. While in fact very few people understand it, actually, as it stands, even as it stood when Darwin expressed it, and even less as we now may be able to understand it in biology.
Jacques Monod (1974)

... I must correct a wrong idea that has been spreading for the past three or four years. It was discovered some years ago that in some cases, the transcription of step from DNA to RNA works in the reverse direction. That is nothing surprising. ... it could be predicted that such events could occur. They do occur, indeed, but this must not be taken to mean that information from protein could possibly go back to the genome. ... I am ready to take any bet you like that this is never going to turn out to be the case.
Jacques Monod (1974) p.394

The privilege of living beings is the possession of a structure and of a mechanism which ensures two things: (i) reproduction true to type of the structure itself, and (ii) reproduction equally true to type, of any accident that occurs in the structure. Once you have that, you have evolution, because you have conservation of accidents. Accidents can then be recombined and offered to natural selection to find out if they are of any meaning or not.
Jacques Monod (1974) p.394

The aspect of evolutionary theory that is unacceptable to many enlightened people, either scientists or philosophers, or idelogists of one kind or another, is the completely contingent aspect which the existence of man, societies, and so on, must take if we accept this theory.
Jacques Monod (1974) p.394

We must conclude that the existence of any particular species is a singular event, an event that occurred only once in the whole of the universe and therefore one that is also basically and completely unpredictable, including that one species which we are, namely man.
Jacques Monod (1974) p.395

While de Vries' and Goldschmidt's views on the origin of species were extreme and unrealistic, from our current knowledge of genetics, de Vries' ideas led Morgan (1925, 1932) to propose a more resonable theory of evolution. ... In his view, selection plays a less important role than mutation, its chief role being to preserve useful mutations and eliminate unfit genotypes. That is, natural selection is regarded merely as a sieve to choose beneficial mutations. For this reason, his theory is often called mutationism, but a better terminology would be mutation-selection theory or classical theory in Dobzansky's sense, since he did not neglect natural selection.
Masatoshi Nei (1987) p.406

At the DNA level, most new genes seem to have been produced by gene duplication and subsequent nucleotide changes .... In these cases, the mutational change of DNA (duplication and nucleotide substitution) is clearly responsible for creating a new gene of character. Natural selection plays no such role. The role of natural selection is to eliminate less fit genotypes and save a beneficial one when there are many different genotypes in the same environment. Therefore, it seems clear that at the molecular level evolution occurs primarily by mutation pressure, though positive selection certainly speeds up gene substitution in populations.
Masatoshi Nei (1987) p.415

... are all individual differences in morphological and physiological characters adaptive as claimed by extreme neo-Darwinians? More than 4 billion people live on this planet, and all of them except identical twins are different with respect to morphological and physiological characters. Are all these differences adaptive? Is random genetic drift unimportant for generating morphological and physiological diversity among organisms? It seems to me that in some morphological characters a substantial part of genetic variation is nonadaptive.
Masatoshi Nei (1987) p.422

In this book, I have examined various aspects of molecular evolution and concluded that mutation is the driving force of evolution at the molecualr level. I have also extended this view to the level of phenotypic evolution and speciation, though I do not deny the importance of natural selection in evolution. I have challenged the prevailing view that a population of organisms contains virtually all sorts of variation and that the only force necessary for a particular character to evolve is natural selection. I have also emphasized the unpredictability of the evolutionary fate of organisms caused by uncontrolable external factors such as rapid climatic changes, geological catastrophes, or even asteroid impacts.
Masatoshi Nei (1987) p.431

The primary cause of evolution is the mutational change of genes. A mutant gene or DNA sequence caused by nucleotide substitution, insertions/delections, recombination, gene conversion, and so forth may spread through the population by genetic drift and/or natural selection and eventually be fixed in the species.
Masatoshi Nei and Sudhir Kumar (2000) p.4

Most new mutations are deleterious, and most mutations with very small effects are likely to be very slightly deleterious. Such mutations are selected against in large populations, but behave as if neutral in small populations.
Tomoko Ohta (1996) p.96

Mutation is a fundamental process for evolution. Under the orthodox view, mutations are raw materials on which natural selection works and organismal evolution is mainly governed by selection. With the accumulation of molecular data, the importance of random drift is being reevaluated. If the effect of a mutant is very small, random drift rather than selection determines its fate.
Tomoko Ohta (1998) p.83

Are we here because of a natural superiority (opposable thumbs, big brains and so on), or are we just plain lucky? In other words, is the evolution of life a fair game, as the survival-of-the-fittest doctrine so strongly implies?
David Raup (1991) p.xi

Is extinction through bad luck a challenge to Darwin's natural selection? No. Natural selection remains the only viable, naturalistic explanation we have for sophisticated adaptations like eyes and wings. We would not be here without natural selection. Extinction by bad luck merely adds another element to the evolutionary process, operating at the level of species, families, and classes, rather than the level of local breeding populations of single species. Thus, Darwinism is alive and well, but, I submit, it cannot have operated by itself to produce the diversity of life today.
David Raup (1991) p.192

Evolution at the molecular level appeared to have properties that would not have been predicted if it were driven by natural selection; and much of molecular evolution is now widely (if not universally) thought to be non-adaptive.
Mark Ridley (1997) p.4

A habit has grown up among some molecular biologists of using homology to mean similarity, regardless of whether the similarity is due to descent from a common ancestor. They thus talk about the "% homology" between two molecules, meaning the percentage of amino acid, or nucleotide sites that are the same in the two molecules. They are often criticized for their unorthodox usage .
M. Ridley (1997) p.208

The working biologist's reaction on learning that evolutionary theory does not fit some philosophical criterion for what a scientific theory should be like is—so much the worse for philosophy.
M. Ridley (1997) p.368

... Kimura's original radical claim, that most molecular evolution proceeds by drift, not selection, remains intact in the nearly neutral theory. It still contrasts strongly with the view that molecular evolution is powered by Darwinian natural selection.
M. Ridley (1997) p.78

Many universes can exist, with all possible combinations of physical laws and constants. In that sense, we just happen to be in the particular one that was suited for the the evolution of our form of life. When cosmologists refer to the anthropic principle, this is all they usually mean. Since we live in this universe, we can assume it possesses qualities suitable for our existence.
Eugenie C. Scott (2004)

... the thesis that evolution is primarily driven by natural selection is sometimes called Darwinism. Unfortunately, many people misapply the term to refer to the concept of descent with modification itself, which is erroneous. Natural selection is not the same as evolution.
Eugenie C. Scott (2004) p.34

Scientists sometimes colloquially refer to macroevolution as "evolution above the species level," but this term does not do justice to the complexity of topics included within the concept.
Eugenie C. Scott (2004) p.183

Micro- and macroevolution are thus different levels of analysis of the same phenomenon: evolution. Macroevolution cannot solely be reduced to microevolution because it encompasses so many other phenomena: adaptive radiation, for example, cannot be reduced only to natural selection, though natural selection helps bring it about.
Eugenie C. Scott (2004) p.183

If God is intervening into our world, he must be doing so in some measurable way. That's what we do with science. We measure.
Michael Shermer (2006)

If a sect does officially insist that its structure of belief demands that evolution be false, then no compromise is possible. An honest and competent biology teacher can only conclude that the sect's beliefs are wrong and that its religion is a false one.
George Gaylord Simpson (1964)

I do not think that evolution is supremely important because it is my speciality. On the contrary, it is my speciality because it is supremely important.
George Gaylord Simpson (1961)

The extreme view that evolution is basically or over all an orthogenetic process is evidence that some scientists' minds tend to move in straight lines, not that evolution does.
George Gaylord Simpson (1949)

Macroevolution is decoupled from microevolution, and we must envision the process governing its course as being analogous to natural selection but operating at a higher level of organization.
Steven M. Stanley (1975) p.648

The microevolutionary process that adequately describes evolution in a population is an utterly inadaquate account of the evolution of the earth's biota. It is inadequate because the evolution of the biota is more than the mutational origin and subsequent survival or extinction of genes in gene pools. Biotic evolution is also the cladogenetic origin and subsequent survival and extinction of gene pools in the biota.
George C. Williams (1992) p.31

I'm not going to be one of these scientists who keep wafling and saying "oh well, science has it's role, religion has it's role... science has it's own kind of truth and religion has it's own kind of truth... somehow, as we work more and more they will somehow come together." I don't believe that for a minute. I don't think that Darwin would have believed it.
Edward O. Wilson

The fundamantal evolutionary event is a change in the frequency of genes and chromosome configurations in a population. If a population of butterflies shifts through time from 40 percent blue individuals to 60 percent individuals, and if the color blue is hereditary, evolution of a simple kind has occurred.
Edward O. Wilson (1992) p.75

That evolution involves nonadaptive differentiation to a large extent at the subspecies level is indicated by the kinds of differences by which such groups are actually distinguished by systematicists. It is only at the subfamily and family levels that clear-cut adaptive differences become the rule. The principal evolutionary mechanisms in the origin of species must thus be an essentially nonadaptive one.
Sewell Wright (1932) p.38

(concerning more evidence for evolution) Some beating of dead horses may be ethical, where here and there they display unexpected twitches that look like life.
Emile Zuckerkandl and Linus Pauling (1965) p.101

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Wednesday, November 25, 2015

In defense of curiosity-motivated research

I was prompted to write this post by three recent events. First, I read an article by Angelika Amon who made A case for more curiosity-driven basic research. She is the recipient of the 2015 ASCB [American Society for Cell Biology] Women in Cell Biology Sandra K. Masur Senior Leadership Award.

She says,
While conducting research to improve the lives of others is certainly a worthy motivation, it is not the main reason why I get up very early in the morning to go to the lab. To me, gaining an understanding of a basic principle in the purest Faustian terms is what I find most rewarding and exciting.

... For me, having a career in curiosity-driven basic research has been immensely rewarding. It is my hope that basic research remains one of the pillars of the American scientific enterprise, attracting the brightest young minds for generations to come. We as a community can help to make this a reality by telling people what we do and highlighting the importance of our work to their lives.
I agree wholeheartedly with this sentiment although I would emphasize that the general public needs to understand that the important result of basic research is knowledge, and knowledge for its own sake is important. It's certainly far better than ignorance.

This kind of scholarly activity—curiosity motivated research—is the backbone of activity in the universities. At least it used to be. I still think that universities should stand up and defend the search for knowledge.

The second stimulus was an acknowledgement I recently stumbled across at the end of a paper by Ford Doolittle from 1982 (Doolittle, 1982).
And I' m most grateful to the Medical Research Council and the Natural Sciences and Engineering Research Council of Canada for providing us with the funds to pursue our sometimes arcane interests without hindrance.
The old MRC has become CIHR. It's hard to imagine any scientist writing such an acknowledgement today since CIHR is notorious for hindering basic curiosity-motivated research [see Support basic research with new leaders at the Canadian Institutes of Health Research (CIHR)].

Not only have the funding agencies abandoned curiosity-motivated research, so have the universities and that brings me to the third event. My university, the University of Toronto, has been trying to direct health research for several decades. It does this by preferentially funding and supporting research in designated areas that are likely to become the beneficiaries of substantial donations and/or support from the private sector. This emphasis often goes hand-in-hand with government wishes and the subverted goals of the funding agencies they control.

The latest example is a new research facility across the street from the main campus in a brand-new, expensive, building that's part of MaRS [U of T expands research facilities in new partnership with MaRS].
The first U of T groups to move over to the new MaRS tower are the Medicine by Design initiative, the Ted Rogers Centre for Heart Research, the Centre for Commercialization of Regenerative Medicine, and the ARCNet advanced research computing and data analytics centre. Other research groups from the Faculty of Medicine will move to MaRS to enhance existing networks in regenerative medicine, drug discovery and infectious disease.
The idea here is to take successful, well-funded, research groups from different campus-based basic science departments and group them together in units that focus on, for example, drug discovery and infectious diseases. They will get all the perks of a new building and new research facilities and enhanced prestige and recognition.

Meanwhile, those researchers working on basic curiosity-motivated projects like Drosophila development, the targeting of cellular RNAs, the survival of mitochondria, theoretical investigations of protein folding, the structure of glycoproteins, and protein turnover in yeast and bacteria—to name just a few—will remain in a 50 year old building that looks more like a prison than a modern research facility. The message is loud and clear. Curiosity-motivated basic researchers are second class scientists unless they just happen to be working on projects that Faculty administrators think are important

That's not how universities should behave. I expect university leaders and administrators to stand up for the search for knowledge and promote the rights of researchers to go where curiosity takes them. That's what academic freedom is all about.

I think you can make a case that grouping like-minded researchers together in specific goal-oriented research groups may not be the most successful strategy in a university environment even if you concede that it's up to universities to pick and choose research priorities. It reminds me of a discussion I had with Janet Stemwedel a few years ago. The discussion started off on the topic of ethics then changed to the difference between "science" and "technology." It applies also to the difference between curiosity-motivated research and goal-oriented research.

Is ‘what is this good for?’ a question to be discouraged?
Teaching Ethics in Science: Science v Technology
A worker in basic scientific research is motivated by a driving curiosity about the unknown. When his explorations yield new knowledge, he experiences the satisfaction of those who first attain the summit of a mountain or the upper reaches of a river flowing through unmapped territory. Discovery of truth and understanding of nature are his objectives. His professional standing among his fellows depends upon the originality and soundness of his work. Creativeness in science is of a cloth with that of the poet or painter.
National Science Foundation (USA) Annual Report 1953
I'm not arguing that scientists who are interested in drug discovery or infectious diseases aren't motivated by curiosity just like the rest of us. What I'm arguing is that it should not be the university's business to reward those whose curiosity leads them in one direction and penalize those who are curious about something else. That's sending a strong message and the message is "go in this direction" if you want the perks. That's not compatible with supporting curiosity-motivated research and the quest for knowledge in its purest form.

Maybe the university needs to stop supporting curiosity-motivated research? That's worth debating but in my experience debate is not what university administrators want to hear. It's rare that professors and researchers are invited to discuss the decisions made in the President's Office or the Dean's Office even though those decisions will seriously affect their lives and their careers.

Why can't we at least discuss these issues rather than read about them in the newspaper?

Doolittle, W.F. (1982) Evolutionary molecular biology: where is it going? Canadian Journal of Biochemistry, 60:83-90.

Support basic research with new leaders at the Canadian Institutes of Health Research (CIHR)

An important article in the Ottawa Citizen calls for the resignation of Alain Beaudet, recently reappointed President of the Canadian Institutes of Health Research (CIHR) ['Demoralized' scientists demand changes at $1B health research agency]. Criticism comes from Michael Rudnicki but he is merely voicing what lots of other researchers feel.
“He has rammed through what he calls reforms which have radically altered the grant delivery system and the system for evaluating grants has been done in a way that distorts the entire process,” said Rudnicki of changes brought in by Beaudet.

Top research scientists from across the country, in interviews with the Citizen, described their mood as demoralized and deeply disturbed by what has been going on at the CIHR. “There is a lot of scorched earth out there,” said one.

According to researchers, the malaise cannot be fixed by simply unmuzzling government scientists. The federal government needs to support basic scientific research, they say, with more money and with a system that is transparent and designed to reward the country’s best and brightest researchers. Instead, researchers say, a series of recent changes at the agency that funds a billion dollars of research each year, notably to the peer review system, have done the opposite.

“The entire research community is very upset and extremely concerned about these changes,” said Rudnicki.

Among concerns are that basic research is getting an ever-smaller share of flatlined funding, in favour of applied or targeted research. Some independent scientists working in labs — doing the kind of work that has led to discoveries such as stem cells — are finding it increasingly difficult to keep going.
The President of CIHR is essentially a government appointee and he or she is not beholding to the researchers (clients) in any legal way. However, I have long advocated that the leadership of CIHR, and the other government funding agencies, should deserve the confidence of the Canadian Research Community and they should resign if they do not have that confidence.

That time has come. Not only has CIHR discouraged basic curiosity-motivated research but the effect of their policies has encouraged university administrators to do the same. We see more and more university resources going into directed research on specific applied targets and the few remaining basic researchers are treated as second class citizens left in the oldest, out-dated, facilities with the fewest university resources.

I will gladly sign any petition calling for the resignation of the CIHR leaders and anyone else who supports their disastrous policies.

Intelligent design creationism and intellectual laziness

I stumbled upon this 2005 letter to Nature by Michael Lynch and I thought I'd share it with you since it emphasizes one of my main pet peeves about intelligent design creationists. I've highlighted the relevant sentences. Check out the video.
Intelligent design or intellectual laziness?

SIR – Much of the concern over ID (Nature 434, 1053 and 1062–1065; 2005) has focused on veiled attempts to inject religion into public education. Sheltered within the confines of academia, most biologists find it hard to believe that the slain need to be slain again. Those in the trenches—school boards, school biology teachers and their national representatives—often don’t know how to respond, in part because they themselves never really achieved a deep understanding of evolutionary biology at college.

However, there is a related and equally disturbing issue: the legitimization of intellectual laziness. Have a problem explaining something? Forget about it: the Designer made it that way. Any place for diversity of opinion as to who/what the Designer is/was? The ID literature makes it very clear that there is no room for scientific discourse on that. Think I’m exaggerating? To get a good idea of what IDers would have the face of science look like, check out the journal Perspectives on Science and Christian Faith (

Two factors have facilitated the promotion of ID. First, IDers like to portray evolution as being built entirely on an edifice of darwinian natural selection. This caricature of evolutionary biology is not too surprising. Most molecular, cell and developmental biologists subscribe to the same creed, as do many popular science writers. However, it has long been known that purely selective arguments are inadequate to explain many aspects of biological diversity. Building a straw man based on natural selection alone makes it easy for opponents to poke holes in evolution. But features of the genome, such as genomic parasites or non-coding introns, which aren’t so evolutionarily favourable (nor obviously ‘intelligent’ innovations), can be more readily explained by models that include random genetic drift and mutation as substantial evolutionary forces.

Second, IDers like to portray evolution as a mere theory. But after a century of close scrutiny, evolutionary theory has passed so many litmus tests of validation that evolution is as much a fact as respiration and digestion.

Less widely appreciated is that evolution has long been the most quantitative field of biology, well grounded in the general principles of transmission genetics. Yet few students at university, and almost none at high school, are exposed to the mathematical underpinnings of evolutionary theory. The teaching of evolution purely as history, with little consideration given to the underlying mechanisms, reinforces the false view that evolution is one of the softer areas of science.

Here is a missed opportunity. Our failure to provide students with the mathematical skills necessary to compete in a technical world is a major concern in the United States. Mathematics becomes more digestible, and even attractive, when students see its immediate application. What better place to start than with the population-genetic theory of evolution, much of which is couched in algebraic terms accessible to school students?

Michael Lynch
Department of Biology, Indiana University,
Bloomington, Indiana 47405, USA

Selfish genes and transposons

Back in 1980, the idea that large fractions of animal and plant genomes could be junk was quite controversial. Although the idea was consistent with the latest developments in population genetics, most scientists were unaware of these developments. They were looking for adaptive ways of explaining all the excess DNA in these genomes.

Some scientists were experts in modern evolutionary theory but still wanted to explain "junk DNA." Doolittle & Sapienza, and Orgel & Crick, published back-to-back papers in the April 17, 1980 issue of Nature. They explained junk DNA by claiming that most of it was due to the presence of "selfish" transposons that were being selected and preserved because they benefited their own replication and transmission to future generations. They have no effect on the fitness of the organism they inhabit. This is natural selection at a different level.

This prompted some responses in later editions of the journal and then responses to the responses.

Here's the complete series ...

Sunday, November 22, 2015

What do pseudogenes teach us about intelligent design?

The human genome has about 14,000 pseudogenes that are derived from protein-coding genes and an unknown number derived from genes that specify functional noncoding RNAs. There is abundant evidence that the vast majority of these pseudogenes are nonfunctional by all measurable criteria.
It would be perverse to deny the existence of pseudogenes. Almost all of them are junk DNA with no known function. Anyone who claims otherwise can be dismissed as a kook and it's not worth debating those people.

The presence of a single well-characterized pseudogene at the same locus in the genomes of different species is powerful evidence of common descent. For example, Ken Miller has long argued that the existence of common pseudogenes in chimpanzees and humans is solid evidence that the two species share a common ancestor. He uses the β-globin pseudogene and the gene for making vitamin C as examples in Only a Theory: Evolution and the Battle for America's Soul.

Friday, November 20, 2015

The truth about ENCODE

A few months ago I highlighted a paper by Casane et al. (2015) where they said ...
In September 2012, a batch of more than 30 articles presenting the results of the ENCODE (Encyclopaedia of DNA Elements) project was released. Many of these articles appeared in Nature and Science, the two most prestigious interdisciplinary scientific journals. Since that time, hundreds of other articles dedicated to the further analyses of the Encode data have been published. The time of hundreds of scientists and hundreds of millions of dollars were not invested in vain since this project had led to an apparent paradigm shift: contrary to the classical view, 80% of the human genome is not junk DNA, but is functional. This hypothesis has been criticized by evolutionary biologists, sometimes eagerly, and detailed refutations have been published in specialized journals with impact factors far below those that published the main contribution of the Encode project to our understanding of genome architecture. In 2014, the Encode consortium released a new batch of articles that neither suggested that 80% of the genome is functional nor commented on the disappearance of their 2012 scientific breakthrough. Unfortunately, by that time many biologists had accepted the idea that 80% of the genome is functional, or at least, that this idea is a valid alternative to the long held evolutionary genetic view that it is not. In order to understand the dynamics of the genome, it is necessary to re-examine the basics of evolutionary genetics because, not only are they well established, they also will allow us to avoid the pitfall of a panglossian interpretation of Encode. Actually, the architecture of the genome and its dynamics are the product of trade-offs between various evolutionary forces, and many structural features are not related to functional properties. In other words, evolution does not produce the best of all worlds, not even the best of all possible worlds, but only one possible world.
How did we get to this stage where the most publicized result of papers published by leading scientists in the best journals turns out to be wrong, but hardly anyone knows it?

Back in September 2012, the ENCODE Consortium was preparing to publish dozens of papers on their analysis of the human genome. Most of the results were quite boring but that doesn't mean they were useless. The leaders of the Consortium must have been worried that science journalists would not give them the publicity they craved so they came up with a strategy and a publicity campaign to promote their work.

Their leader was Ewan Birney, a scientist with valuable skills as a herder of cats but little experience in evolutionary biology and the history of the junk DNA debate.

The ENCODE Consortium decided to add up all the transcription factor binding sites—spurious or not—and all the chromatin makers—whether or not they meant anything—and all the transcripts—even if they were junk. With a little judicious juggling of numbers they came up with the following summary of their results (Birney et al., 2012) ..
The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.
See What did the ENCODE Consortium say in 2012? for more details on what the ENCODE Consortium leaders said, and did, when their papers came out.

The bottom line is that these leaders knew exactly what they were doing and why. By saying they have assigned biochemical functions for 80% of the genome they knew that this would be the headline. They knew that journalists and publicists would interpret this to mean the end of junk DNA. Most of ENCODE leaders actually believed it.

That's exactly what happened ... aided and abetted by the ENCODE Consortium, the journals Nature and Science, and gullible science journalists all over the world. (Ryan Gregory has published a list of articles that appeared in the popular press: The ENCODE media hype machine..)

Almost immediately the knowledgeable scientists and science writers tried to expose this publicity campaign hype. The first criticisms appeared on various science blogs and this was followed by a series of papers in the published scientific literature. Ed Yong, an experienced science journalist, interviewed Ewan Birney and blogged about ENCODE on the first day. Yong reported the standard publicity hype that most of our genome is functional and this interpretation is confirmed by Ewan Birney and other senior scientists. Two days later, Ed Yong started adding updates to his blog posting after reading the blogs of many scientists including some who were well-recognized experts on genomes and evolution [ENCODE: the rough guide to the human genome].

Within a few days of publishing their results the ENCODE Consortium was coming under intense criticism from all sides. A few journalists, like John Timmer, recongized right away what the problem was ...
Yet the third sentence of the lead ENCODE paper contains an eye-catching figure that ended up being reported widely: "These data enabled us to assign biochemical functions for 80 percent of the genome." Unfortunately, the significance of that statement hinged on a much less widely reported item: the definition of "biochemical function" used by the authors.

This was more than a matter of semantics. Many press reports that resulted painted an entirely fictitious history of biology's past, along with a misleading picture of its present. As a result, the public that relied on those press reports now has a completely mistaken view of our current state of knowledge (this happens to be the exact opposite of what journalism is intended to accomplish). But you can't entirely blame the press in this case. They were egged on by the journals and university press offices that promoted the work—and, in some cases, the scientists themselves.

[Most of what you read was wrong: how press releases rewrote scientific history]
Nature may have begun to realize that it made a mistake in promoting the idea that most of our genome was functional. Two days after the papers appeared, Brendan Maher, a Feature Editor for Nature, tried to get the journal off the hook but only succeeded in making matters worse [see Brendan Maher Writes About the ENCODE/Junk DNA Publicity Fiasco].

Meanwhile, two private for-profit companies, illumina and Nature, team up to promote the ENCODE results. They even hire Tim Minchin to narrate it. This is what hype looks like ...

Soon articles began to appear in the scientific literature challenging the ENCODE Consortium's interpretation of function and explaining the difference between an effect—such as the binding of a transcription factor to a random piece of DNA—and a true biological function.

Eddy, S.R. (2012) The C-value paradox, junk DNA and ENCODE. Current Biology, 22:R898. [doi: 10.1016/j.cub.2012.10.002]

Niu, D. K., and Jiang, L. (2012) Can ENCODE tell us how much junk DNA we carry in our genome?. Biochemical and biophysical research communications 430:1340-1343. [doi: 10.1016/j.bbrc.2012.12.074]

Doolittle, W.F. (2013) Is junk DNA bunk? A critique of ENCODE. Proc. Natl. Acad. Sci. (USA) published online March 11, 2013. [PubMed] [doi: 10.1073/pnas.1221376110]

Graur, D., Zheng, Y., Price, N., Azevedo, R. B., Zufall, R. A., and Elhaik, E. (2013) On the immortality of television sets: "function" in the human genome according to the evolution-free gospel of ENCODE. Genome Biology and Evolution published online: February 20, 2013 [doi: 10.1093/gbe/evt028

Eddy, S.R. (2013) The ENCODE project: missteps overshadowing a success. Current Biology, 23:R259-R261. [10.1016/j.cub.2013.03.023]

Hurst, L.D. (2013) Open questions: A logic (or lack thereof) of genome organization. BMC biology, 11:58. [doi:10.1186/1741-7007-11-58]

Morange, M. (2014) Genome as a Multipurpose Structure Built by Evolution. Perspectives in biology and medicine, 57:162-171. [doi: 10.1353/pbm.2014.000]

Palazzo, A.F., and Gregory, T.R. (2014) The Case for Junk DNA. PLoS Genetics, 10:e1004351. [doi: 10.1371/journal.pgen.1004351]

By March 2013—six months after publication of the ENCODE papers—some editors at Nature decided that they had better say something else [see Anonymous Nature Editors Respond to ENCODE Criticism]. Here's the closest thing to an apology that they have ever written ....
The debate over ENCODE’s definition of function retreads some old battles, dating back perhaps to geneticist Susumu Ohno’s coinage of the term junk DNA in the 1970s. The phrase has had a polarizing effect on the life-sciences community ever since, despite several revisions of its meaning. Indeed, many news reports and press releases describing ENCODE’s work claimed that by showing that most of the genome was ‘functional’, the project had killed the concept of junk DNA. This claim annoyed both those who thought it a premature obituary and those who considered it old news.

There is a valuable and genuine debate here. To define what, if anything, the billions of non-protein-coding base pairs in the human genome do, and how they affect cellular and system-level processes, remains an important, open and debatable question. Ironically, it is a question that the language of the current debate may detract from. As Ewan Birney, co-director of the ENCODE project, noted on his blog: “Hindsight is a cruel and wonderful thing, and probably we could have achieved the same thing without generating this unneeded, confusing discussion on what we meant and how we said it”.
Oops! The importance of junk DNA is still an "important, open and debatable question" in spite of what the video sponsored by Nature might imply.

(To this day, neither Nature nor Science have actually apologized for misleading the public about the ENCODE results. [see Science still doesn't get it ])

The ENCODE Consortium leaders responded in April 2014—eighteen months after their original papers were published.

Kellis, M., Wold, B., Snyder, M.P., Bernstein, B.E., Kundaje, A., Marinov, G.K., Ward, L.D., Birney, E., Crawford, G. E., and Dekker, J. (2014) Defining functional DNA elements in the human genome. Proc. Natl. Acad. Sci. (USA) 111:6131-6138. [doi: 10.1073/pnas.1318948111]

In that paper they acknowledge that there are multiple meanings of the word function and their choice of "biochemical" function may not have been the best choice ....
However, biochemical signatures are often a consequence of function, rather than causal. They are also not always deterministic evidence of function, but can occur stochastically.
This is exactly what many scientists have been telling them. Apparently they did not know this in September 2012.

They also include in their paper a section on "Case for Abundant Junk DNA." It summarizes the evidence for junk DNA, evidence that the ENCODE Consortium did not acknowledge in 2012 and certainly didn't refute.

In answer to the question, "What Fraction of the Human Genome Is Functional?" they now conclude that ENCODE hasn't answered that question and more work is needed. They now claim that the real value of ENCODE is to provide "high-resolution, highly-reproducible maps of DNA segments with biochemical signatures associate with diverse molecular functions."
We believe that this public resource is far more important than any interim estimate of the fraction of the human genome that is functional.
There you have it, straight from the horse's mouth. The ENCODE Consortium now believes that you should NOT interpret their results to mean that 80% of the genome is functional and therefore not junk DNA. There is good evidence for abundant junk DNA and the issue is still debatable.

I hope everyone pays attention and stops referring to the promotional hype saying that ENCODE has refuted junk DNA. That's not what the ENCODE Consortium leaders now say about their results.

Casane, D., Fumey, J., et Laurenti, P. (2015) L’apophénie d’ENCODE ou Pangloss examine le génome humain. Med. Sci. (Paris) 31: 680-686. [doi: 10.1051/medsci/20153106023]

Different kinds of pseudogenes: Polymorphic pseudogenes

There are three main kinds of pseudogenes: processed pseudogenes, duplicated pseudogenes, and unitary pseudogenes [Different kinds of pseudogenes - are they really pseudogenes?].

There's one sub-category of pseudogenes that deserves mentioning. It's called "polymorphic pseudogenes." These are pseudogenes that have not become fixed in the genome so they exist as an allele along with the functional gene at the same locus. Some defective genes might be detrimental, representing loss-of-function alleles that compromise the survival of the organism. Lots of genes for genetic diseases fall into this category. That's not what we mean by polymorphism. The term usually applies to alleles that have reached substantial frequency in the population so that there's good reason to believe that all alleles are about equal with respect to natural selection.

Polymorphic pseudogenes can be examples of pseudogenes that are caught in the act of replacing the functional gene. This indicates that the functional gene is not under strong selection. For example, a newly formed processed pseudogene can be polymorphic at the insertion site and newly duplicated loci may have some alleles that are still functional and others that are inactive. The fixation of a pseudogene takes a long time.

Different kinds of pseudogenes: Unitary pseudogenes

The most common types of pseudogenes are processed pseudogenes and those derived from gene duplication events [duplicated pseudogenes].

The third type of pseudogene is the "unitary" pseudogene. Unitary pseudogenes are genes that have no parent gene. There is no functional gene in the genome that's related to the pseudogene.

Unitary psedogenes arise when a normally functional gene becomes inactivated by mutation and the loss of function is not detrimental to the organism. Thus, the mutated, inactive, gene can become fixed in the population by random genetic drift.

The classic example is the gene for L-glucono-γ-lactone oxidase (GULO), a key enzyme in the synthesis of vitamin C (L-ascorbate, ascorbic acid). This gene is functional in most vertebrate species because vitamin C is required as a cofactor in several metabolic reactions; notably, the processing of collagen [Vitamin C]. This gene has become inactive in primates so primates cannot synthesize Vitamin C and must obtain it from the food they eat.

A pseudogene can be found at the locus for the L-glucono-γ-lactone oxidase gene[GULOP = GULO Pseudogene]. It is a highly degenerative pseudogene with multiple mutations and deletions [Human GULOP Pseudogene]

This is a unitary pseudogene. Unitary pseudogenes are rare compared to processed pseudogenes and duplicated pseudogenes but they are distinct because they are not derived from an existing, functional, parent gene.

Note: Intelligent design creationists will go to great lengths to discredit junk DNA. They will even attempt to prove that the GULO pseudogene is actually functional. Jonathan Wells devoted an entire chapter in The Myth of Junk DNA to challenging the idea that the GULO pseudogene is actually a pseudogene. A few years ago, Jonathan McLatchie proposed a mechanism for creating a functional enzyme from the bits and pieces of the human GULOP pseudogene but that proved embarrasing and he retracted [How IDiots Would Activate the GULO Pseudogene] Although some scientists are skeptical about the functionality of some pseudogenes, they all accept the evidence showing that most psuedogenes are nonfunctional.

Different kinds of pseudgogenes: Duplicated pseudogenes

Of the three different kinds of pseudogenes, the easiest kind of pseudogene formation to understand is simple gene duplication followed by inactivation of one copy. [see: Processed pseudogenes for another type]

I've assumed, in the example shown below, that the gene duplication event happens by recombination between sister chromosomes when they are aligned during meiosis. That's not the only possibility but it's easy to understand.

These sorts of gene duplication events appear to be quite common judging from the frequency of copy number variations in complex genomes (Redon et al., 2006; MacDonald et al., 2013).

Wednesday, November 18, 2015

Different kinds of pseudogenes: Processed pseudogenes

Let's look at the formation of a "processed" pseudogene. They are called "processed" because they are derived from the mature RNA produced by the functional gene. These mature RNAs have been post-transcriptionally processed so the pseudogene resembles the RNA more closely than it resembles the parent gene.

This is most obvious in the case of processed pseudogenes derived from eukaryotic protein-coding genes so that's the example I'll describe first.

In the example below, I start with a simple, hypothetical, protein-coding gene consisting of two exons and a single intron. The gene is transcribed from a promoter (P) to produce the primary transcript containing the intron. This primary transcript is processed by splicing to remove the intron sequence and join up the exons into a single contiguous open reading frame that can be translated by the protein synthesis machinery (ribosomes plus factors etc.).1 [See RNA Splicing: Introns and Exons.]

Different kinds of pseudogenes - are they really pseudogenes?

I define a gene as "DNA sequence that is transcribed to produce a functional product" [What Is a Gene? ]. Genes can encode proteins or the final product can be a functional RNA other than mRNA.

A pseudogene is a broken gene that cannot produce a functional RNA. They are called "pseudogenes" because they resemble active genes but carry mutations that have rendered them nonfunctional. The human genome contains about 14,000 pseudogenes related to protein-coding genes according to the latest Ensembl Genome Reference Consortium Human Genome build [GRCh38.p3]. There's some controversy over the exact number but it's certainly in that ballpark.1

The GENCODE Pseudogene Resource is the annotated database used by Ensembl and ENCODE (Pei et al. 2012).

There are an unknown number of pseudogenes derived from genes for noncoding functional RNAs. These pseudogenes are more difficult to recognize but some of them are present in huge numbers of copies. The Alu elements in the human genome are derived from 7SL RNA and there are similar elements in the mouse genome that are derived from tRNA genes.

There are three main classes of pseudogenes and one important subclass. The categories apply to pseudogenes derived from protein-coding genes and to those derived from genes that specify functional noncoding RNAs. I'm going to describe each of the categories in separate posts. I'll mostly describe them using a protein-coding gene as the parent.

1. Processed pseudogenes [Processed pseudogenes ]
2. Duplicated pseudogenes [Duplicated pseudogenes ]
3. Unitary pseudogenes
4. subclass: Polymorphic pseudogenes

Saturday, November 14, 2015

Which animals have barely evolved according to National Geographic?

Liz Langley of National Geographic has posted an article on their website: Which Animals Have Barely Evolved?.

The answers are the platypus and the opossum. The overall impression she conveys to the general public is that these species have not evolved for millions and millions of years.

I don't agree. I think it's important to teach the general public that such statements flatly contradict modern evolutionary theory. If, in fact, we discovered modern species that showed no signs of having evolved for millions of years, this would refute modern evolutionary theory.

The accepted minimal definition of evolution is ... [What Is Evolution?]
Evolution is a process that results in heritable changes in a population spread over many generations.
... or something similar like "change in the frequency of alleles in a population."

The main accepted mechanisms of evolution are natural selection and random genetic drift.

The only way positive natural selection1 can stop is if an organism is so perfectly adapted to its current environment (external and internal) that every possible mutation is either deleterious or neutral. That includes all metabolic processes and every structure in the cell.

Nobody could rationally advocate such a claim.

The only way to stop random genetic drift is if there's no such thing as a new neutral or nearly neutral mutation and all such variation in the population has been eliminated.

No evolutionary biologist could possibly make such a claim with a straight face.

It's easy to test such ridiculous claims by looking at the genomes of the opossum and the platypus. The evidence shows that they have evolved at the same rate as all other species.

The article actually mentions this problem ...
“'Unchanged' is a tricky word,” Nizar Ibrahim, a paleontologist at the University of Chicago and 2014 National Geographic Explorer, says via email.

With only fossils to go by, scientists can examine an ancient animal's skeletal structure, but it's not the whole story. Physiology and DNA change somewhat over time, he says, both through the basic process of evolution as well as random genetic changes.

That said, two mammals that have undergone the fewest evolutionary shifts are the platypus and the opossum, says Samantha Hopkins, associate professor of geology at the University of Oregon.
Liz Langley did not pick up on this comment so she missed a wonderful teaching moment.

It's possible that Liz Langley isn't aware of modern evolutionary theory and that she actually believes that evolution comes to a halt as long as species live in a relatively constant environment. It's possible that she disagrees with the minimal definition of evolution and prefers a definition that only counts significant changes in external phenotype. Or, it's possible that she thinks that National Geographic readers can't handle modern evolutionary theory. If it's the latter, I disagree.

1. You can't stop negative natural selection unless there are no new deleterious mutations. That's also impossible.

Friday, November 13, 2015

Cornelius Hunter predicts that there's going to be function found for the vast majority of the genome according to the intelligent design paradigm

Listen to this Podcast where Casey Luskin interviews Dr. Cornelius Hunter.1 It's only 9 minutes long.

Dr. Cornelius Hunter on ENCODE and "Junk" DNA, Part 2

Here's part of the transcript.
Casey Luskin: ... and, as we all know, or many ID the Future listeners probably know, for years Darwinian theorists and evolutionary scientists have said that our genomes ought to be full of junk if evolution is true


Casey Luskin: So, Dr. Hunter, you think, just for the record, that in the long term there is going to be function found for probably the vast majority of the genome and so, maybe, you might call it a prediction you would make coming out of an intelligent design paradigm. Is that correct?

Cornelius Hunter: Yes, that's correct Casey, I'll definitely go on the record on that. Not to say I have a hundred percent confidence and also I wanna be clear that from a metaphysical perspective, from my personal belief, I don't have a problem wherever it lands. It doesn't matter to me whether it's 10% or 90% or any where in between or 100% ... just from the scientific perspective and just from the history of science and the history of what we've found in biology, it really does look like it's gonna be closer to 100 than zero.

Casey Luskin: Okay, great, I always like it when people put clear and concrete predictions out there and and I think that's very helpful.

I predict that about 90% of our genome will turn out to be junk DNA—DNA with no function. I base my prediction on the scientific perspective and the history of what we've found in biology. That's interesting because Cornelius Hunter and I are apparently reaching opposite conclusions based on the same data.

I also love it when people make predictions. Will the intelligent design paradigm be falsified if I turn out to be right?

Does it sound to you that Cornelius Hunter personally doesn't care if the prediction coming out of the intelligent design paradigm is correct or not?

1. How come in the podcast they never refer to Dan Graur as Dr. Graur? Isn't that strange?