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Thursday, December 10, 2015

How many human protein-coding genes are essential for cell survival?

The human genome contains about 20,000 protein-coding genes and about 5,000 genes that specify functional RNAs. We would like to know how many of those genes are essential for the survival of an individual and for long-term survival of the species.

It would be almost as interesting to know how many are required for just survival of a particular cell. This set is the group of so-called "housekeeping genes." They are necessary for basic metabolic activity and basic cell structure. Some of these genes are the genes for ribosomal RNA, tRNAs, the RNAs involved in splicing, and many other types of RNA. Some of them are the protein-coding genes for RNA polymerase subunits, ribosomal proteins, enzymes of lipid metabolism, and many other enzymes.

The ability to knock out human genes using CRISPR technology has opened to door to testing for essential genes in tissue culture cells. The idea is to disrupt every gene and screen to see if it's required for cell viability in culture.

Three papers using this approach have appeared recently:
Blomen, V.A., Májek, P., Jae, L.T., Bigenzahn, J.W., Nieuwenhuis, J., Staring, J., Sacco, R., van Diemen, F.R., Olk, N., and Stukalov, A. (2015) Gene essentiality and synthetic lethality in haploid human cells. Science, 350:1092-1096. [doi: 10.1126/science.aac7557 ]

Wang, T., Birsoy, K., Hughes, N.W., Krupczak, K.M., Post, Y., Wei, J.J., Lander, E. S., and Sabatini, D.M. (2015) Identification and characterization of essential genes in the human genome. Science, 350:1096-1101. [doi: 10.1126/science.aac7041]

Hart, T., Chandrashekhar, M., Aregger, M., Steinhart, Z., Brown, K.R., MacLeod, G., Mis, M., Zimmermann, M., Fradet-Turcotte, A., and Sun, S. (2015) High-Resolution CRISPR Screens Reveal Fitness Genes and Genotype-Specific Cancer Liabilities. Cell 163:1515-1526. [doi: 10.1016/j.cell.2015.11.015]
Each group identified between 1500 and 2000 protein-coding genes that are essential in their chosen cell lines.

One of the annoying things about all three papers is that they use the words "gene" and "protein-coding gene" as synonyms. The only genes they screened were protein-coding genes but the authors act as though that covers ALL genes. I hope they don't really believe that. I hope it's just sloppy thinking when they say that their 1800 essential "genes" represent 9.2% of all genes in the genome (Wang et al. 2015). What they meant is that they represent 9.2% of protein-coding genes.

By looking only at genes that are essential for cell survival, they are ignoring all those genes that are specifically required in other cell types. For example, they will not identify any of the genes for olfactory receptors or any of the genes for keratin or collagen. They won't detect any of the genes required for spermatogenesis or embryonic development.

What they should detect is all of the genes required in core metabolism.

The numbers seen too low to me so I looked for some specific examples.

The HSP70 gene family encodes the major heat shock protein of molecular weight 70,000. The protein functions as a chaperone to help fold other proteins. They are among the most highly conserved genes in all of biology and they are essential. The three genes for the normal cellular proteins are HSPA5 (Bip, the ER protein); HSPA8 (the cytoplasmic version); and HSPA9 (mitochondrial version). All three are essential in the Blomen et al. paper. Only HSPA5 and HSPA9 are essential in Hunt et al. (This is an error.) (I can't figure out how to identify essential genes in the Wang et al. paper.)

There are two inducible genes, HSPA1A and HSPA1B. These are the genes activated by heat shock and other forms of stress and they churn out a lot of HSP70 chaperone in order to save the cells. There are not essential genes in the Blomen et al. paper and they weren't tested in the Hunt et al. paper. This is an example of the kind of gene that will be missed in the screen because the cells were not stressed during the screening.

I really don't like these genomics papers because all they do is summarize the results in broad terms. I want to know about specific genes so I can see if the results conform to expectations.

I looked first at the genes encoding the enzymes for gluconeogenesis and glycolysis. The results are from the Blomen et al. paper. In the figure below, the genes names in RED are essential and the ones in blue are not.


As you can see, at least one of the genes for the six core enzymes is essential. But none of the other genes is essential. This is a surprise since I expect both pathways (gluconeogenesis and glycolysis) to be active and essential in those cells. Perhaps the cells can survive for a few days without making these enzymes. It means they can't take up glucose because one of the hexokinase enzymes should be essential.

These result suggest that the Blomen et al. study is overlooking some important essential genes.

Now let's look at the citric acid cycle. All of the enzymes should be essential.


That's very strange. It's hard to imagine that cells in culture can survive without any of the genes for the subunits of the pyruvate dehydrogenase complex or the subunits of the succinyl C0A synthetase complex. Or malate dehydrogenase, for that matter.

Something is wrong here. The study must be missing some important essential genes. I wish the authors had looked at some specific sets of genes and told us the results for well-known genes. That would allow us to evaluate the results. Perhaps this sort of thing isn't done when you are in "genomics" mode?

The "core fitness" protein-coding genes that were identified are more highly conserved than the other genes and they tend to be more highly expressed. They also show lower levels of variation within the human population. This is consistent with basic housekeeping features.

Each group identified several hundred unannotated genes in their core sample. These are genes with no known function (yet).

The results of the three studies do not overlap precisely but most of the essential genes were common to all three analyses.


Wednesday, December 09, 2015

Why doesn't natural selection reduce the mutation rate to zero?

All living organisms have developed highly accurate DNA replication complexes and sophisticated mechanisms for repairing DNA damage. The combination results in DNA replication errors that are about 1 per 10 billion base pairs (10-10 per bp). DNA damage due to other factors is effectively repaired with an error rate of 1 in 100 per base pair (10-2 per bp).

Mutations can be beneficial, deleterious, or neutral. In organisms with large genomes there are many more neutral mutations than the other two classes but in organisms with smaller genomes a higher percentage of mutations are either beneficial or deleterious. In all cases, there are more deleterious mutations than beneficial ones.

If deleterious mutations are harmful to the individual then natural selection should favor a low mutation rate in order to minimize that effect. This is especially true in large multicellular organisms where somatic cell mutations cause cancer and other problems. It seems logical that the optimal mutation rate should be zero in order to maximize the survival of the individual and its offspring.

Nothing in biology makes sense except in the light of population genetics.

Michael Lynch
But even though the number of beneficial mutations is low compared to those that are deleterious, this is the stuff of adaptive evolution. In the long run the population will become more fit if beneficial mutations occur and become fixed by natural selection. Eliminating mutations might provide a short-term advantage but eventually the population will go extinct if it can't adapt to new environments. (Neutral and deleterious mutations can also contribute to adaptation over the long term.)

The simplest explanation for this apparent paradox is that there's a trade-off between selection to minimize deleterious mutations and selection for long-term evolutionary advantage. The problem with that explanation is that it is very difficult to show how you can select for the future benefit of mutations to the species (population). It seems as though you have to invoke two bogeymen; group selection and teleology.

Maybe there's a better explanation?

Jerry Coyne recently thought about this problem and posted his analysis under the provocative title: The irony of natural selection. He concludes that there's some constraint that limits the ability of natural selection to achieve a zero mutation rate.
The most probable explanation is that evolution does not produce perfect adaptations. In the case of mutations, though natural selection favors individuals most able to repair any changes in DNA (although a small percentage of these might be adaptive), this level of perfection cannot be achieved because of constraints: the cost of achieving perfection, the fact that all errors are impossible to detect or remove, or that some cells (i.e., sperm or eggs) may not even have DNA-repair mechanisms because of genetic or physiological constraints.
I used to think that this was the best explanation. I taught my students that the accuracy of DNA replication, for example, comes at the cost of speed. The more accurate the polymerization process, the slower it takes. This makes a lot of sense and there's experimental support for the claim. Slowing down the time it takes to replicate the genome will affect the time it takes for cell divisions and that could be harmful ... or so the argument goes.

Unfortunately, I ran into Michael Lynch at an evolution meeting and he quickly destroyed that argument. There's no evidence that the speed of DNA replication is limiting the rate of cell divisions and, besides, there are easy ways for selection to get around such a limitation if it ever occurred. (This is a photo of Michael Lynch looking at me right after setting me straight. He's wondering how I could have been so stupid.)

When you think about it, there doesn't seem to be any biochemical or physiological constraints that could prevent the mutation rate from getting to zero ... or at least a lot closer than it is now.

Michael Lynch has a better answer and he explains it in a paper titled: "The Lower Bound to the Evolution of Mutation Rates" (Lynch, 2011).
As the mutation rate is driven to lower and lower levels by selection, a point must eventually be reached where the advantage of any further increase in replication fidelity is smaller than the power of random genetic drift (Lynch 2008, 2010). The goal here is to evaluate the extent to which such an intrinsic barrier can provide an adequate explanation for the patterns of mutation rates known to have evolved in natural populations.
The main "constraint" is the limited power of natural selection in the presence of random genetic drift. This will depend to some extent of the size of the population.

This idea is called the "drift-barrier hypothesis. It is described in Sung et al. (2012):
... the drift-barrier hypothesis predicts that the level of refinement of molecular attributes, including DNA replication fidelity and repair, that can be accomplished by natural selection will be negatively correlated with the effective population size (Ne) of a species. Under this hypothesis, as natural selection pushes a trait toward perfection, further improvements are expected to have diminishing fitness advantages. Once the point is reached beyond which the effects of subsequent beneficial mutations are unlikely to be large enough to overcome the power of random genetic drift, adaptive progress is expected to come to a standstill. Because selection is generally expected to favor lower mutation rates as a result of the associated load of deleterious mutations, and because the power of drift is inversely proportional to Ne, lower mutation rates are expected in species with larger Ne.
The Lynch lab has produced lots of evidence in support of the hypothesis although there may be some confounding factors in some populations.

The bottom line is that the real irony of natural selection is that it's just not powerful enough to reduce the error rate of replication and repair below the values we currently see.

In a sense, it's the "error rate" of fixation by natural selection in the face of random genetic drift that allows evolution to occur.

The more we learn about biology the more we learn that it's messy and sloppy at every level. Evolution is not a watchmaker and it's not even a blind watchmaker. It's a tinkerer1 and the "watch" barely keeps time.


Image Credit: The Mendel's traits image is from Wikispaces Classroom.

1. Jacob, F. (1977) Evolution and tinkering. Science (New York, NY), 196:1161. [PDF]

Lynch, M. (2011) The lower bound to the evolution of mutation rates. Genome Biology and Evolution, 3:1107. [doi: 10.1093/gbe/evr066]

Sung, W., Ackerman, M.S., Miller, S.F., Doak, T.G., and Lynch, M. (2012) Drift-barrier hypothesis and mutation-rate evolution. Proc. Natl. Acad. Sci. (USA) 109:18488-18492. [doi: 10.1073/pnas.1216223109]

Thursday, December 03, 2015

Facts and theories of evolution according to Dawkins and Coyne

Sometime back in the pre-Cambrian (before blogs) there was a newsgroup called talk.origins—it still exists. In 1993 I wrote a little essay that tried to convince creationists1 of the difference between facts of evolution and evolutionary theory [Evolution is a Fact and a Theory]. I relied heavily on Stephen Jay Gould's essay on "Evolution as Fact and Theory" originally published in Discover magazine in 1981 and re-printed in Hen's Teeth and Horse's Toes.

I updated my thoughts on Gould's essay in 2007 [Evolution Is a Fact and a Theory] and added some more comment on the 30th anniversary [Evolution Is a Fact and a Theory].

Lot's of other people have presented their take on the facts and theories of evolution. Here's one from Richard Lenski and another from Ryan Gregory.

Monday, November 30, 2015

Celebrating Lucy Maud Montgomery

Today Google celebrates the birthday of Lucy Maud Montgomery (November 30, 1874 – April 24, 1942). She is the author of Anne of Green Gables and other books.

Lucy Maud Montgomery was born in Prince Edward Island (Canada) and after getting her teaching certificate from Prince of Wales College in Charlottetown (P.E.I.) she attended Dalhousie University in Halifax (Nova Scotia, Canada) before taking up a teaching position in P.E.I. That's when she wrote Anne of Green Gables (1908).

In 1911 she married a Presbyterian minister, Ewen Macdonald, and moved to Uxbridge, Ontario (northeast of Toronto). In 1926, she and her husband moved to Norval, Ontario, a small village due north of where I live in Mississauga, Ontario. We've passed her house many times. She lived there until 1935 when she moved to Swansea, Ontario, now a part of western Toronto between the Humber River and High Park. She died there in 1942 and was buried in P.E.I.

Lucy Maud Montgomery is a distant cousin of mine. I descend from the Coles. The genealogy is confusing but at some point in time a Mr. Cole and his wife Mary (maiden name unknown) came to North America, probably New York. Their son, Benjamin Cole, is my great4-grandfather. Mr. Cole died sometime around 1765 and Mary married George Penman. The history is confusing, they may have lived in New England and moved to P.E.I. just before or after the American Revolution. They self-identify as United Empire Loyalists.

Mary is my great5 grandmother and she had several children with George Penman. Two of them were Nancy (b. 1768) and Elizabeth ("Betsy") (b. 1769). Nancy married Donald Montgomery of the "New Moon" farm in Malpeque, P.E.I. (Emily of New Moon). Her sister married David Murray.

Donald Montgomery, the son of Nancy & Donald, married his first cousin Ann Murray, daughter of Elizabeth & David. Their son, Hugh John Montgomery, was Lucy Maud Montgomery's father.

Thus, Lucy Maud Montgomery's great grandmother is my great-great-great-great-great grandmother.





Sunday, November 29, 2015

Motoo Kimura calculates a biochemical mutation rate in 1968

I recently had occasion to re-read a paper by Motoo Kimura from 1968. (Kimura, 1968). I noticed, for the first time, that he estimates a mutation rate based on his understanding of the error rate of DNA replication. He also makes a comment about creationists.

Remember, this was in 1968 and we didn't know as much then as we do now. Kimura took note of the fact that evolutionary trees based on comparing amino acid sequences gave rates of amino acid substitutions that seemed far too high. His conclusion is in the abstract.

Friday, November 27, 2015

Hawker Hurricanes and Typhoons in World War II

Last week we went to the Canadian Warplane Heritage Museum in Hamilton, Ontario (Canada) with our grandson Luca [see The Latest Excursion]. Here I am with Luca standing beside a Hawker Hurricane from World War II.

My father, F/L Laurence Victor "Vic" Kirsch,1 was a fighter pilot in World War II and he flew Hurricanes and, later, rocket-firing Hawker Typhoons with the RAF 164 Squadron known as the Argentine British Squadron because of the volunteers from Argentina. (My father was seconded from the RCAF (Canada)).

Here's a picture of him (below) in the cockpit of one of his planes.


I have his log books. The first page (right) shows him flying Hurricanes ("Hurry") in sorties over France in December 1943. This was just when the squadron was preparing to switch to Typhoons and become specialists in ground support in preparation for D-Day.

The next entries (below) are facing pages from June, 1944. Note the entry for June 6, 1944. On the left is "DER TAG" in red and on the right is "LONG AWAITED 2nd FRONT IS HERE." The entry for June 5th reads, "Deas and self flew to Cherbourg and reported the weather. Flew over the invasion fleet, impressive sight. Hundreds of naval craft and A/C cover. Wouldn't have missed this sight for the world. Dark when we landed and silly old Deas practised landing on his belly."

The entry for June 6th (D-Day) reads, "Followed SQDN across channel. Saw hundreds of ships. Jumped by 90's."

On June 14th (one week after D-Day) the squadron lands at their new base in Crépon, France.





1. He died in a plane crash when I was four months old. My mother remarried and I was adopted by my stepfather, K.R. Moran.

Thursday, November 26, 2015

Quotations

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 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 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.
Motoo 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.
Motoo 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

Motoo 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.
Motoo 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.
Motoo 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 (www.asa3.org/ASA/PSCF.html).

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.