Science Literature

Alongside all the public interest in sporting prowess, recent research has added significantly to our knowledge of how the human body actually works. Many characteristics we take for granted now appear to be critical success factors. Take, for example, our toes. We do not need long toes, like monkeys and apes, because our toes are not used for grasping branches. But are they vestigial - withered remnants of once-grand appendages? The answer is: most definitely not! Whilst it is possible to walk comfortably with longer toes, running is different. Increase toe length by just 20% and there is a doubling of the peak digital flexor impulses and the mechanical work required.

An image like this shows just how different the human foot is from the apes (Source here)

It emerges that the human body has numerous traits that all support the ability to run. In an informative piece in the New York Times, author Parker-Pope refers to the research into short toes saying that it:

"showed that the short toes of the human foot allowed for more efficient running, compared with longer-toed animals. Increasing toe length as little as 20 percent doubles the mechanical work of the foot. Even the fact that the big toe is straight, rather than to the side, suggests that our feet evolved for running. "The big toe is lined up with the rest, not divergent, the way you see with apes and our closest non-running relatives," Dr. Bramble said. "It's the main push-off in running: the last thing to leave the ground is that big toe." Spring-like ligaments and tendons in the feet and legs are crucial for running. (Our close relatives the chimpanzee and the ape don't have them.) A narrow waist and a midsection that can turn allow us to swing our arms and prevent us from zigzagging on the trail. Humans also have a far more developed sense of balance, an advantage that keeps the head stable as we run. And most humans can store about 20 miles' worth of glycogen in their muscles."

A few years ago, one of the authors, Daniel Lieberman, was involved in a related study. This was concerned with the gluteus maximus, said to be the the largest muscle in the human body. Parker-Pope also reports on this work, which found that the gluteus maximus is primarily engaged during running.

"Your butt is a running muscle; you barely use it when you walk," Dr. Lieberman said. "There are so many features in our bodies from our heads to our toes that make us good at running."

There would appear to be potential for clarifying the use of this muscle. It is important for posture, and another has made the comment: "As all weightlifters know, the primary purpose of the gluteus maximus is to raise the body from a deep squat." There is more to be said on these matters.

A noticeable element of this research is that the data are consistently interpreted in terms of natural selection pressures acting on natural variation. This is nothing unusual, because most biologists working in this field have come to accept Darwinism as their interpretative paradigm. Richard Dawkins speaks for many when he wrote in The Blind Watchmaker (Chapter 3) that "We have seen that living things are too improbable and beautifully designed to have come into existence by chance." Natural selection is perceived as giving direction to hereditable variation and results in incremental adaptation. This is how Lieberman and his colleagues approach the 'evolution' of short toes:

"The data suggest that having longer pedal phalanges, in the hallux and to some extent in the lateral toes, increases digital flexor force and work and might contribute to an increased risk of overuse injury during running. Although these effects presumably have negligible fitness consequences for habitually shod recent-modern humans who do not run long distances daily, they might have been significant enough to impose the kind of selective pressures that led to the observed changes in phalangeal size and shape during human evolution. For example, partial foot remains recovered at Hadar, Ethiopia, suggest that, by 3.6 million years ago, the lateral phalanges of A. afarensis were shorter than in the African great apes, but approximately 40% longer and more curved than in modern humans. This intermediate phalangeal morphology is thought to reflect a mixed behavioral repertoire comprising substantial arboreality and facultative terrestrial bipedalism."

What makes this a matter for concern is that no one appears to be talking about testing alternative hypotheses. It is as though the Darwinian explanation wins by default, and this does not make for healthy science. In particular, one hypothesis that is held by a great many people but is not admitted to academic debate, is that the human body is a product of intelligent design. The strength of this approach rests (a) in the holistic character of the alleged design; (b) the exquisite nature of the various characteristics; and (c) the claim that some of these features are irreducibly complex. (as in chapter 2 of Stuart Burgess' book The Origin of Man.

There are ways to test the Darwinian hypothesis. The presumed ancestor had elongated foot bones, illustrated here. To transform this stage to a short-toed human foot by natural selection demands gradual change and this is how the hypothesis can be tested. Where is the evolutionary pathway? Incidentally, the australopithecine feet should not be compared with the African great apes (as Lieberman) but with other ancestral apes contemporary with Australopithecus afarensis. This same line of reasoning about hypothesis testing means that design-based predictions of abrupt appearance can also be evaluated. Are evolutionists willing to allow this testing process to occur? Is this a debate that can be permitted in academic literature and in educational contexts?

Almost invariably, in the past, the idea that ID leads to testable hypotheses is blocked by the philosophical principle that all causes in science must be natural (law or chance). Despite repeated efforts to point out this is a metaphysical block, not one required by science, few take the time to address the point. However, it is encouraging to find some shifts in opinion from time to time. An example, surprising to most of us, is the concession Richard Dawkins gave to John Lennox in a debate last year.

"The deist god would be one that I think it would be [pause] one could make a reasonably respectable case for that. Not a case that I would accept, but I think it is a serious discussion that we could have." (The audio of this exchange can be accessed via http://www.fixed-point.org)

This is a welcome acknowledgement. For those wanting more input on this, the day after the debate, Melanie Phillips had an article in Spectator Magazine drawing attention to the significance of Dawkins' admission. The offer of a serious discussion is welcome. ID scientists do not ask for anything more than the freedom to present a respectable case. What is needed is for academics to abandon their doctrinaire attachment to methodological materialism in science.

Another perspective on this issue is to consider what needs to be done to build a robot that walks and runs. This task certainly focuses the mind and clarifies the issues. For an insight into the state-of-the-art, go here. PETMAN is wearing normal athletic shoes and exhibits a normal heel-to-toe gait. This robot is the product of intelligent design: many man-hours of effort by highly skilled scientists and engineers. Those who think natural selection acting on natural variations would do well to consider the immensity of the task they are expecting Darwin's mechanisms to accomplish.

Walking, running and the evolution of short toes in humans
Campbell Rolian, Daniel E. Lieberman, Joseph Hamill, John W. Scott and William Werbel
Journal of Experimental Biology 212, 713-721 (2009) | doi: 10.1242/jeb.019885

Abstract: The phalangeal portion of the forefoot is extremely short relative to body mass in humans. This derived pedal proportion is thought to have evolved in the context of committed bipedalism, but the benefits of shorter toes for walking and/or running have not been tested previously. Here, we propose a biomechanical model of toe function in bipedal locomotion that suggests that shorter pedal phalanges improve locomotor performance by decreasing digital flexor force production and mechanical work, which might ultimately reduce the metabolic cost of flexor force production during bipedal locomotion. We tested this model using kinematic, force and plantar pressure data collected from a human sample representing normal variation in toe length (N=25). The effect of toe length on peak digital flexor forces, impulses and work outputs was evaluated during barefoot walking and running using partial correlations and multiple regression analysis, controlling for the effects of body mass, whole-foot and phalangeal contact times and toe-out angle. Our results suggest that there is no significant increase in digital flexor output associated with longer toes in walking. In running, however, multiple regression analyses based on the sample suggest that increasing average relative toe length by as little as 20% doubles peak digital flexor impulses and mechanical work, probably also increasing the metabolic cost of generating these forces. The increased mechanical cost associated with long toes in running suggests that modern human forefoot proportions might have been selected for in the context of the evolution of endurance running.

See also:

Lieberman, D.E., Raichlen, D.A., Pontzer, H., Bramble D.M. and Cutright-Smith, E., The human gluteus maximus and its role in running, Journal of Experimental Biology 209, 2143-2155 (2006) | doi: 10.1242/jeb.02255

Parker-Pope, T., The Human Body Is Built for Distance, New York Times (October 26, 2009)

Darwinius masillae is the magnificently preserved Ida, the "eighth wonder of the world" unveiled earlier this year: "our Mona Lisa" and an evolutionary "Rosetta Stone". Afradapis is a newly discovered adapoid from Egypt, known from fossilised jaws and teeth. The controversies surrounding Ida have been the subject of comment here and here. A newly published cladistic analysis of 360 morphological features found in 117 living and extinct primates comes down on the side of Ida being more closely related to lemurs and lorises rather than ancestral to anthropoids.

Darwinius was proposed to be on the right branch - an ancestor of apes and humans - but the new study puts it as a dead end on the left branch (Source here)

One of the criticisms of the original report of Darwinius is that the authors did not provide a comprehensive cladistic analysis, but only referred to anthropoid-like characters. That analysis is still not forthcoming, but a new paper by Seiffert and colleagues considers dentition and jaw morphological features for a comprehensive set of primates, including Darwinius. The claim for anthropoid-like characters is put in a new light, because so many adapiform animals (ancestors of lemurs and lorises) have them.

"It has long been known that some adapiform lineages evolved derived morphological features that are also seen in living and extinct anthropoids (for example, fused mandibular symphyses, upper canines with mesial grooves, enlarged and spatulate upper and lower incisors, short and tall rostra). The phylogenetic significance of these features has been a source of ongoing debate for decades."

Their significant finding is that Afradapis (their newly reported fossil species - an undisputed adapiform) has numerous anthropoid-like characters. This leads the authors to conclude that evolutionary convergences are in plentiful supply.

"Of all known fossil prosimians (including Darwinius), Afradapis provides perhaps the most detailed examples of derived anthropoidlike adaptations in its dental and mandibular morphology. As is the case for many of the morphological features that some have argued link adapiforms to anthropoids, however, the anthropoid-like features of Afradapis (fused mandibular symphysis with transverse torus, deep mandibular corpus, deep masseteric fossa, large upper molar hypocones, absence of P2/2 and presence of an enlarged P3 with a honing facet for the upper canine) are not present in the most primitive undoubted fossil anthropoids, such as Biretia and Proteopithecus, indicating that the features are likely to have been acquired through convergent evolution."

The implication, then is that the Darwinius team have been misled by characters that have turned out not to be diagnostic of anthropoid affinities. This conclusion has been picked up and discussed by many commentators, such as Gibbons:

"When they scored Ida and Afradapis against those other primates, Seiffert and colleagues found that adapids do share some traits with anthropoids, such as the loss of a third upper and lower premolar. But these traits evolved more than once among primates, the team reports tomorrow in Nature. They are the result of convergent evolution, which is the acquisition of the same biological trait in unrelated lineages - and, thus, do not indicate inheritance of the trait from a shared ancestor."

Several significant consequences follow from this research. Not least is the reminder that tracking human ancestors by identifying missing links is an exercise fraught with methodological difficulties. As has been previously noted, human evolution data can be likened to a pointillist painting. Like a pointillist painting, evolution is only apparent from a distant vantage point. Close up, we see masses of data, but no coherent picture.

Another issue to address concerns convergent evolution and the problems this phenomenon creates for cladistic analyses. How do we know what characters are primitive and what are derived? Here is an opportunity for human interpretation to be concealed behind a scientific analysis. The extent to which convergences can be invoked raises suspicion in the minds of some:

"One of the researchers who studied Ida, however, responds that Ida and Afradapis look more like the group that gave rise to anthropoids than the group that gave rise to lemurs and lorises - and that there are too many traits to dismiss as convergent evolution. "The complete convergence postulated for Afradapis seems implausible to me," says paleontologist Philip Gingerich of the University of Michigan, Ann Arbor."

The best outcome of all this is for scientists to demonstrate more humility in handling data. So many seem to grasp at some data and brandish 'evidence' as though it provides a definitive answer to controversy. But this is not how data should be handled in research. Data needs to be interpreted and history shows that there is always more than one way of interpreting it. If we can all adopt a 'multiple working hypotheses' approach when using the scientific method, it will be progress indeed.

Convergent evolution of anthropoid-like adaptations in Eocene adapiform primates
Erik R. Seiffert, Jonathan M. G. Perry, Elwyn L. Simons & Doug M. Boyer
Nature 461, 1118-1121 (22 October 2009) | doi:10.1038/nature08429

Adapiform or 'adapoid' primates first appear in the fossil record in the earliest Eocene epoch (~55 million years (Myr) ago), and were common components of Palaeogene primate communities in Europe, Asia and North America1. Adapiforms are commonly referred to as the 'lemur-like' primates of the Eocene epoch, and recent phylogenetic analyses have placed adapiforms as stem members of Strepsirrhini, a primate suborder whose crown clade includes lemurs, lorises and galagos. An alternative view is that adapiforms are stem anthropoids. This debate has recently been rekindled by the description of a largely complete skeleton of the adapiform Darwinius, from the middle Eocene of Europe, which has been widely publicised as an important 'link' in the early evolution of Anthropoidea. Here we describe the complete dentition and jaw of a large-bodied adapiform (Afradapis gen. nov.) from the earliest late Eocene of Egypt (~37 Myr ago) that exhibits a striking series of derived dental and gnathic features that also occur in younger anthropoid primates [. . .] The specialized morphological features that these adapiforms share with anthropoids are therefore most parsimoniously interpreted as evolutionary convergences. [. . .]

See also:

Gibbons, A., New Primate Fossil Poses Further Challenge to Ida, ScienceNOW Daily News (21 October 2009)

Dalton, R., Fossil primate challenges Ida's place, (21 October 2009), 461, 1040 | doi:10.1038/4611040a

Shallow water light ranges from the ultraviolet to red (wavelengths 360 nm - 650 nm). Going deeper, the extremes disappear and the spectrum narrows to a blue (approx 480 nm). Of the fish species whose colour vision has been tested to date, all except one can see in the ultraviolet (UV). The exception is the scabbardfish, which is the subject of a new research paper. The authors find that the fish that are sensitive to UV have a pigment that absorbs UV light, but the scabbardfish lacks this pigment and has, instead, a pigment that is violet-sensitive.

The scabbardfish (Lepidopus fitchi) is now the only fish known to have switched from ultraviolet to violet vision, or the ability to see blue light. (Credit: Carol Clark, Emory University) (Source ScienceDaily)

The researchers have looked at the molecular structure of the relevant pigments and their absorption spectra.

"[T]hey used genetic engineering, quantum chemistry and theoretical computation to compare vision proteins and pigments from scabbardfish and another species, lampfish. The results indicated that scabbardfish shifted from UV to violet vision by deleting the molecule at site 86 in the chain of amino acids in the opsin protein.
"Normally, amino acid changes cause small structure changes, but in this case, a critical amino acid was deleted," Yokoyama says."

The hypothesis is that the shift from UV to violet vision was adaptive. Since the lampfish is also a benthopelagic marine fish, the adaptation explanation must also address why the lampfish has retained UV vision.

"Scabbardfish spend much of their life at depths of 25 to 100 meters, where UV light is less intense than violet light, which could explain why they made the vision shift, Yokoyama theorizes. Lampfish also spend much of their time in deep water. But they may have retained UV vision because they feed near the surface at twilight on tiny, translucent crustaceans that are easier to see in UV light."

The researchers found several other amino acid sequence variants that could not be linked to any change in function. This stimulated some salutary comments from the authors:

"It is very common that evolutionary biologists infer the possibility of adaptive evolution of various genes by using computer programs, which compare the nonsynonymous and synonymous nucleotide substitutions per site. However, these analyses not only predict a significant number of false-positives but also fail to predict many positively selected sites; consequently, the positively selected amino acid changes inferred by the statistical methods must be tested by using experimental methods."

In the Press Release, Yokoyama is quoted as saying: "Evolutionary biology is filled with arguments that are misleading, at best". The research team is to be commended for connecting changes in amino acid sequences with changes in phenotypes and then relating all to the living environments. This is good science and a big contrast from the story-telling approach. Adaptation can be studied in a rigorous way, and analyses like this are a demonstration of what is possible.

The words "evolutionary" and "evolution" are used by the authors in their paper. It is strange that evolutionary biology has a fixation of the e-word when there are so many different meanings given to it. In this case, we have a study of adaptive change involving the change of a single amino acid in the opsin protein. This can be understood as a means of the organism becoming fine-tuned to its environment. Darwinian mechanisms appear to be adequate for understanding the data. It should not be necessary to point out that 'fine-tuning' is qualitatively different from 'constructing' the visual apparatus of the organism. Fine-tuning is only possible when the eye is functioning. This point can be better appreciated when the change involves the deletion of existing biological information - as it is in this case. Adaptation is not the route to create biological novelties: microevolution is not macroevolution.

There is a design-orientated way of approaching these data. What if organisms are designed to vary so that they can adapt to changes in their environment? In such cases, mechanisms for fine-tuning can be understood as designed mechanisms, thereby shifting the focus away from the biological world being the product of chance + necessity and towards a world resulting from purposeful intelligent agency.

Evolutionary replacement of UV vision by violet vision in fish
Takashi Tada, Ahmet Altun and Shozo Yokoyama
Proceedings of the National Academy of Sciences, October 13, 2009, 106(41), 17457-17462 | DOI: 10.1073/pnas.0903839106

Abstract: The vertebrate ancestor possessed ultraviolet (UV) vision and many species have retained it during evolution. Many other species switched to violet vision and, then again, some avian species switched back to UV vision. These UV and violet vision are mediated by short wavelength-sensitive (SWS1) pigments that absorb light maximally ([lamda]max) at approximately 360 and 390-440 nm, respectively. It is not well understood why and how these functional changes have occurred. Here, we cloned the pigment of scabbardfish (Lepidopus fitchi) with a [lamda]max of 423 nm, an example of violet-sensitive SWS1 pigment in fish. Mutagenesis experiments and quantum mechanical/molecular mechanical (QM/MM) computations show that the violet-sensitivity was achieved by the deletion of Phe-86 that converted the unprotonated Schiff base-linked 11-cis-retinal to a protonated form. The finding of a violet-sensitive SWS1 pigment in scabbardfish suggests that many other fish also have orthologous violet pigments. The isolation and comparison of such violet and UV pigments in fish living in different ecological habitats will open an unprecedented opportunity to elucidate not only the molecular basis of phenotypic adaptations, but also the genetics of UV and violet vision.

See also:

Seeing Blue: Fish Vision Discovery Makes Waves In Evolutionary Biology, ScienceDaily (17 October 2009)

Tyler, D. Adaptations affecting dim-light vision in vertebrates, ARN Literature blog (10 September 2008)

When I took a course leading to the Certificate of Higher Education, we had some lecture inputs on psychology. The rationale was to show how educational strategies can be informed by the findings of psychologists. My abiding memory of these lectures concern the way the thinking of Sigmund Freud was presented: I was astounded that the lecturer was so uncritical of Freundianism. It was as though the great man was an oracle and we were expected to absorb his words rather than appraise them. At the time of taking the course, I was aware that Freud was no scientist. He did not test out his ideas using an experimental approach. Rather, he used his ideology-based theory as a filter through which to interpret the data. It was a useful experience for me - reinforcing the distinction between ideology and empirically based science.

In view of this, I welcomed reading the concerns expressed in an editorial in the current Nature. The opening paragraph reads:

"Anyone reading Sigmund Freud's original works might well be seduced by the beauty of his prose, the elegance of his arguments and the acuity of his intuition. But those with a grounding in science will also be shocked by the abandon with which he elaborated his theories on the basis of essentially no empirical evidence. This is one of the main reasons why Freudian-style psychoanalysis has long since fallen out of fashion: its huge expense - treatment can stretch over years - is not balanced by evidence of efficacy."

Disillusionment with Freud has not led to a better understanding of humanity (source here)

The stimulus for the editorial was a report issued by a report into the current status and future prospects of clinical psychology in the US. This found that a very high proportion of practitioners put more emphasis on their personal experience than on scientific evidence. This leads to a situation where craft practices prevail and interest in science is low. The US is not alone with these problems: go here and here.

"[M]any psychologists continue to use unproven therapies that have no clear outcome measures - including, in extreme cases, such highly suspect regimens as 'dolphin-assisted therapy'."

Questions are raised in the Editorial about the educational programmes leading to professional qualifications. The American Psychological Association is the accrediting body for the United States and Canada. However:

"The APA requires that such courses have a scientific component, but it does not require that science be as central as some members would like. In frustration, representatives of some two-dozen top research-focused graduate-training programmes grouped together in 1994 to form the Academy of Psychological Clinical Science (APCS), with a mission to promote scientific psychology."

The Editorial points out the scientific advances that could support clinical psychology: neuroimaging, molecular and behavioural genetics, and cognitive neuroscience. However, the link between the science and clinical practice is not explained, and it is worth asking whether the lukewarmness of practitioners towards science is because they have not been able to translate the science into therapeutic interventions. These practitioners are pragmatists: they are looking for therapies that they can use. They will not need to be brow-beaten into using scientific psychology if the findings are relevant to their profession.

Without wishing to denigrate in any way the empirical work being done in science laboratories, there is a problem with the theoretical framework adopted by most researchers. Here is one psychologist writing about free-will and his perception of science:

"[T]here can be no such thing as free will for the committed scientist, in his or her professional life. Thus, science itself presupposes that every phenomenon has a cause. We may speak of "spontaneous combustion" or a "spontaneous abortion" or even "spontaneous applause", but in each of these cases, some cause is more than likely . . . it is essential to a sober, naturalistic worldview." (Source here)

In this quote, the writer says that "science itself presupposes that every phenomenon has a cause", but he means that every phenomenon has a natural cause. He refers to a naturalistic worldview. Now this is a real problem. Instead of science being a search for truth, the writer is using science to pre-empt discussion about causation. But what if there are intelligent causes as well as natural ones? How would naturalistic science ever know? The author quotes Daniel Dennett approvingly:

"By trying to answer the questions, by sketching out the non-miraculous paths that can take us all the way from senseless atoms to freely chosen actions, we open up handholds for the imagination. The compatibility of free will and science . . . is not as inconceivable as it once seemed."

The issue is not one of introducing the miraculous to science (which is an impossible scenario) but insisting that there is continuity from senseless atoms to conscious humanity. By excluding intelligent causation, naturalistic science is making a statement about the nature of reality. The assertion does not emerge by the use of the scientific method, but is a dogmatic imposition. Unfortunately, this materialistic mindset is widespread among behavioural geneticists and neuroscientists. If their philosophical stance is wrong, and there are no checks and balances in their science, then they will never understand the human condition. This does not give confidence that their work will lead to therapeutic interventions that will help patients.

This is not to defend "unproven therapies" but to flag up a problem not mentioned in the Editorial. Freud imposed theory onto data, but so also does naturalistic science. We need to be encouraging a science that is free to explore the evidence wherever it leads and which builds into its methodologies the means to challenge its most cherished presuppositions.

Current Status and Future Prospects of Clinical Psychology
Timothy B. Baker, Richard M. McFall, and Varda Shoham.
Psychological Science in the Public Interest, 9(2), November 2008, 67-103.

Excerpt from Summary: Clinical psychologists' failure to achieve a more significant impact on clinical and public health may be traced to their deep ambivalence about the role of science and their lack of adequate science training, which leads them to value personal clinical experience over research evidence, use assessment practices that have dubious psychometric support, and not use the interventions for which there is the strongest evidence of efficacy. Clinical psychology resembles medicine at a point in its history when practitioners were operating in a largely prescientific manner.

Psychology: a reality check
Editorial
Nature 461, 847 (15 October 2009) | doi:10.1038/461847a

Abstract: If clinical psychology in the United States wants to remain viable and relevant in today's health systems, it needs to publicly embrace science.

For more blogs on the nature of humanity, go here, here and here.

Evolutionary theory does not boast of many laws, and those that do are not universal by any means. One of these is Dollo's law, which is said to date back to about 1890. It is really a hypothesis about the non-reversibility of evolutionary pathways. The authors of new research considered the relevance of the law to the molecular evolution of a protein structure and reported a significant constraint preventing reversibility.

"The extent to which our observations concerning the evolutionary reversibility of glucocorticoid receptors can be generalized to other proteins requires further research. We predict that future investigations, like ours, will support a molecular version of Dollo's law: as evolution proceeds, shifts in protein structure-function relations become increasingly difficult to reverse whenever those shifts have complex architectures [. . .]"

A few restrictive mutations meant the key would not turn (Source here)

A description of the work is provided by Carl Zimmer in The New York Times:

"Dr. Thornton and his colleagues [. . .] studied a protein called a glucocorticoid receptor that helps humans and most other vertebrates cope with stress by grabbing a hormone called cortisol and then switching on stress-defense genes. By comparing the receptor to related proteins, the scientists reconstructed its history. Some 450 million years ago, it started out with a different shape that allowed it to grab tightly to other hormones, but only weakly to cortisol. Over the next 40 million years, the receptor changed shape, so that it became very sensitive to cortisol but could no longer grab other hormones. During those 40 million years, Dr. Thornton found, the receptor changed in 37 spots, only 2 of which made the receptor sensitive to cortisol. Another 5 prevented it from grabbing other hormones. When he made these 7 changes to the ancestral receptor, it behaved just like a new glucocorticoid receptor.
Dr. Thornton reasoned that if he carried out the reverse operation, he could turn a new glucocorticoid receptor into an ancestral one. So he and his colleagues reversed these key mutations to their old form. To Dr. Thornton's surprise, the experiment failed. "All we got was a completely dead receptor," he said."

To find out why the receptor was inactive, the researchers looked for other mutations - and found 5. These were described as "restrictive" because when attempts were made to return the receptor to its supposed ancestral form, the additional mutations acted as blocks.

"Dr. Thornton argues that once the restrictive mutations evolved, they made it practically impossible for the receptor to evolve back to its original form. The five key mutations could not be reversed first, because the receptor would be rendered useless. Nor could the seven restrictive mutations be reversed first. Those mutations had little effect on how the receptor grabbed hormones. So there was no way that natural selection could favor individuals with reversed mutations."

Some significant comments on this research have been made by Michael Behe here and here. These comments are highly relevant to discussions of mechanisms of evolutionary transformation. At the outset, Behe said that the work was interesting and the conclusion was reasonable -

"but the result was exceedingly modest and well within the boundaries that an intelligent design proponent like myself would ascribe to Darwinian processes. After all, the starting point was a protein which binds several steroid hormones, and the ending point was a slightly different protein that binds the same steroid hormones with slightly different strengths. How hard could that be?"

Behe's central point is that the evolutionary pathway was relatively easily disrupted by a few other mutations, so it is not satisfactory to think that Darwinian processes can find a way over every hurdle. The conclusions of his first post are as follows:

* The central point of The Edge of Evolution was that if several amino acids of a protein must be changed before a certain selective effect is available, then that is effectively beyond the reach of Darwinian processes. Bridgham et al (2009) confirm that conclusion. [. . .]
* There is no reason to think the protein studied by Bridgham et al (2009) is unusual in its difficulty of developing a binding site for even a relatively closely-related substance. In fact, in the absence of strong opposing data, that should be the default, reasonable assumption.
* That same reasonable assumption counts strongly against any two unrelated proteins easily developing a binding site for each other.
* That reasonable assumption therefore negates all woolly Darwinian evolutionary scenarios where critical protein binding sites are assumed without justification to pop up when needed (such as, say, in the building of multiprotein structures like the cilium or flagellum).
* Thus the work strongly supports the conclusion of Edge that Darwinian processes are highly unlikely to have built the complex molecular machinery of the cell.

The conclusion of the second post is this:

"The bottom line is that, for a given evolutionary task, at best only a handful of proteins will likely be helpful to evolve, at worst none may help. To calculate the probability of, say, a helpful protein-protein interaction developing in response to any particular selective pressure, it's mistaken to gratuitously multiply odds by the total number of proteins in a cell. Combined with the point made by Bridgham et al (2009), that even tiny structural/functional changes may not be achievable by random mutation/selection, these considerations pretty much squelch the likelihood of Darwinian processes doing much of significance during evolution."

An epistatic ratchet constrains the direction of glucocorticoid receptor evolution
Jamie T. Bridgham, Eric A. Ortlund & Joseph W. Thornton
Nature 461, 515-519 (24 September 2009) | doi:10.1038/nature08249

The extent to which evolution is reversible has long fascinated biologists. Most previous work on the reversibility of morphological and life-history evolution has been indecisive, because of uncertainty and bias in the methods used to infer ancestral states for such characters. Further, despite theoretical work on the factors that could contribute to irreversibility, there is little empirical evidence on its causes, because sufficient understanding of the mechanistic basis for the evolution of new or ancestral phenotypes is seldom available. By studying the reversibility of evolutionary changes in protein structure and function, these limitations can be overcome. Here we show, using the evolution of hormone specificity in the vertebrate glucocorticoid receptor as a case-study, that the evolutionary path by which this protein acquired its new function soon became inaccessible to reverse exploration. Using ancestral gene reconstruction, protein engineering and X-ray crystallography, we demonstrate that five subsequent 'restrictive' mutations, which optimized the new specificity of the glucocorticoid receptor, also destabilized elements of the protein structure that were required to support the ancestral conformation. Unless these ratchet-like epistatic substitutions are restored to their ancestral states, reversing the key function-switching mutations yields a non-functional protein. Reversing the restrictive substitutions first, however, does nothing to enhance the ancestral function. Our findings indicate that even if selection for the ancestral function were imposed, direct reversal would be extremely unlikely, suggesting an important role for historical contingency in protein evolution.

See also:

Behe, M. Nature Publishes Paper on the Edge of Evolution, Evolution News & Views, 30 September 2009

Behe, M. Nature Paper Reaches "Edge of Evolution" and Finds Darwinian Processes Lacking, Evolution News & Views, 7 October 2009

Dolgin, E. Protein burns its evolutionary bridges, Nature News, 23 September 2009 | doi:10.1038/news.2009.940