09/26/08

Permalinkby 11:57:13 am, Categories: Literature - Articles, 853 words   English (UK)

The emerging field of DNA nanotechnology

The challenges of working at the nanometre level of detail is one that few people can even comprehend. Despite all the media interest in these new technologies, and despite hearing explanations of the first principles many times, it is still mind-blowing! It is not so surprising, therefore, that people have turned to the natural world, where nano-sized machinery is operating within every cell, and where the variety of mechanisms provides a powerful stimulus for innovation.

"[N]ature illustrates that we are nowhere near the limit of exquisite control over organization; it possesses an extraordinary capacity to assemble complex nanostructures with active and specialized functions. Our ability to precisely position components on the nanometer scale the way nature does, and to do so in a parallel rather than a serial manner, is still limited and is a key goal in nanotechnology and materials science."

DNA Origami in Nature
Results of some early stage research on DNA nanotechnology.

A review paper has just appeared, looking at the potential of DNA nanotechnology. In the natural world, DNA provides materials for self-assembly and the coordination of the process. Can this be utilised by nanotechnologists working with sequences they have put together. The answer is a resounding yes.

"Of the natural self-assembling molecules, DNA is arguably the most remarkable. A cooperative interplay of hydrogen-bonding, [pi]-stacking, electrostatic, and hydrophobic interactions drives one DNA strand to assemble with its complement into a double helix according to extremely precise base-pairing rules. Additional attributes, such as rigidity on the nanoscale, a diameter of ~2 nm, and a near-infinite number of potential sequences, extend DNA's reach beyond a genetic blueprint for life. DNA is emerging as an attractive tool for nanoscience as well; it is a highly promising template for organizing nanomaterials in a programmable way."

The review is well worth reading and there is little merit in summarising. Researchers have moved from 1D molecules to 2D and 3D structures. A great variety of techniques have been developed, providing a rich toolbox for nano-construction projects. "It is of note that in structural DNA nanotechnology, DNA is used to provide all the parameters for self-assembly: connectivity, structural features, and programmability." Synthetic DNA sequences can be made to fold in predetermined ways.

"Hairpins were incorporated into stapling strands to write words, such as "DNA," and to draw complex objects, such as the outline of the Western Hemisphere. DNA origami will be useful for accessing larger DNA shapes with highly addressable surfaces."

Of particular interest is where this research is heading. There are two major challenges: "the correction of errors that arise in DNA assembly, and the replication and scale-up of DNA nanostructures." Regarding error correction:

"As the complexity of DNA assemblies increases, so will the number of the DNA sequences required to form them. This will necessitate using overlapping, degenerate strands that may assemble into undesirable products. Biological systems have developed a number of elegant strategies to proofread and remove errors during and after assembly. Inspired by these systems, Lu used an approach in which deoxyribozymes (DNAzymes) specifically locate and cleave misassembled structures in gold nanoparticle assemblies. In the presence of the "correct" DNA strands, the DNAzyme is not properly folded and is inactive; however, in the presence of the "incorrect" DNA strands, the DNAzyme is properly folded and proceeds to cleave and remove the errors."

Scaling-up again draws inspiration from biological systems. Throughout the review, "Nature" is portrayed as an agent. Nature does this and Nature does that. When such sophistication is on display, it is difficult to insist on the natural world being a Blind Watchmaker - the product of 'chance and necessity'. This research is crying out for a foundation in design-thinking. Even with our best efforts as intelligent agents, we are just scratching the surface of what we find in living things. Nanotechnology in the natural world reveals exquisite design, not the products of tinkering. It deserves to be credited as the product of intelligent agency!

"Nature builds complexity in a hierarchical way. It progressively increases length scales and relies on a number of noncovalent interactions, including DNA base-pairing, to drive assembly. Supramolecular DNA assembly is a means to weave in principles of hierarchical complexity and new interactions into DNA nanostructures, and opens the door to assembling more diverse functional structures with greater ease."

Assembling Materials with DNA as the Guide
Faisal A. Aldaye, Alison L. Palmer, and Hanadi F. Sleiman
Science 321, 26 September 2008: 1795-1799.

Abstract: DNA's remarkable molecular recognition properties and structural features make it one of the most promising templates to pattern materials with nanoscale precision. The emerging field of DNA nanotechnology strips this molecule from any preconceived biological role and exploits its simple code to generate addressable nanostructures in one, two, and three dimensions. These structures have been used to precisely position proteins, nanoparticles, transition metals, and other functional components into deliberately designed patterns. They can also act as templates for the growth of nanowires, aid in the structural determination of proteins, and provide new platforms for genomics applications. The field of DNA nanotechnology is growing in a number of directions, carrying with it the promise to substantially affect materials science and biology.

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09/25/08

Permalinkby 10:25:33 am, Categories: Literature - Articles, 808 words   English (UK)

A "teachable moment" regarding the departure of Michael Reiss

When big mistakes are made, time for reflection is well spent. The departure of Professor Michael Reiss from the post of Education Director of the Royal Society counts as a big, big mistake. In an Editorial in Nature, the media are called to account:

"The headlines were damning. [. . .] The reports were wrong. [. . .] Nature was not privy to the conversations between the reporters and editors responsible for this story, so we will leave it to them to consider how such a gross misrepresentation could have happened, and what lessons to draw from it."

Teaching the birds
A teachable moment - but will anything be learned? (Source here)

The Editorial suggests there are lessons to be learned, but is not prepared to say what those lessons are. However, this is not good enough! Media reporters are not fools, making stories up. They have been encouraged by science leaders to respond to Creationism and Intelligent Design in quite specific ways: lumping them together as the same message, declaring them to be dogma and alien to science, etc. None of this is true, but that's what the science journalists have been groomed to write. So when Michael Reiss comes along saying things that could have been said by a Creationist or an ID advocate, he was treated like an apostate from the community of science.

What about the Royal Society, the public statements of some of its Fellows, and the behind-the-scenes crisis talks? "Nor was Nature privy to the Royal Society's internal deliberations about Reiss, so we will leave it to the officers and fellows of that body to reflect on who has done the most to damage its reputation." Although it is clear that the Editors of Nature are not impressed by the conduct of the Royal Society, they do not suggest any specific lessons to be learned. This is an inadequate response. They could easily have pointed out that Reiss' academic freedom has been overridden by 3 Nobel laureates and others who insisted in his removal. These men cannot be allowed the luxury of saying 'we misunderstood what Reiss was saying' - if they had misunderstood him, they have had ample time to realise their mistake and he ought to be reinstated by now. No, they disagreed profoundly with Reiss' position and they wanted him out. This bigotry matches the vitriol documented against ID advocates in the film Expelled. Antagonism towards anyone who does not conform to the secularist view of science is intense.

The Editors of Nature try to associate Reiss' counsel with that of Eugenie Scott in California:

"Those who argue that allowing discussion of creationism in a science class gives it legitimacy, and that students who ask about it should be firmly directed to take their questions elsewhere, are misguided.
Eugenie Scott, executive director of the National Center for Science Education in Oakland, California, [. . .] points out that in the real world, any such shut-up-and-take-it-elsewhere response from the teacher will inevitably be perceived by the student (and his or her classmates) as a humiliating personal put-down. It will obstruct rather than encourage enquiry and understanding. It will also invite complaints from outraged parents.
What is more, it will squander what experienced educators like to call 'a teachable moment'. All too often, that moment is the one opportunity that a school has to engage resistant students and introduce them to what science has to say."

However, Eugenie Scott does not capture the heart of Reiss' message - which is not based at all on pragmatism. Reiss identifies creationism as a worldview. He identifies ID as a worldview. Within these alternative worldviews, data takes on different meanings. Observed evidences of variation in nature do not count as evidence for macroevolution; homology carries a design message and does not necessarily point to common ancestry; creation-based biology or design-based biology is regarded as testable. To say these approaches to the evidence are "scientifically nonsensical creationist beliefs" goes contrary to the point Reiss has been making. Trying to equate his principled thinking to the pragmatism of Eugenie Scott suggests confusion about these issues. For more on this, go here.

The Michael Reiss incident is a good example of a "teachable moment". There are lessons for science journalists, Royal Society Fellows, and the Editors of Nature. Will this moment be squandered by fudging the issues that have stirred this debate?

Creation and classrooms
Editorial
Nature 455, 431-432 (25 September 2008) | doi:10.1038/455431b

Abstract: Better to confront superstition with science than to disregard the superstitious.

First para: The headlines were damning. "Leading scientist urges teaching of creationism in schools," proclaimed Britain's The Times newspaper on 12 September, echoing the headlines appearing that day in numerous other British media. The stories asserted that Michael Reiss, a biologist and educational researcher, an ordained Anglican minister and (at the time) the education director of the Royal Society, had explicitly advocated that state-school biology classes teach creationism.

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09/19/08

Permalinkby 08:44:35 am, Categories: Literature - Articles, 1059 words   English (UK)

Another call to counter the Forces of Ignorance

It seems that every organisation connected with science has leaders who feel the need to make statements opposing intelligent design and creationism. Whilst most of these get no further than the press release, one has made it to the pages of Genome Biology. The author is Gregory Petsko, President of the American Society for Biochemistry and Molecular Biology (ASBMB ). The first paragraph sets the tone: "the Discovery Institute, that bastion of ignorance, right-wing political ideology, and pseudo-scientific claptrap, the creationist movement has mounted yet another assault on science." The "assault on science" is considered to be partly propaganda and partly legislative. Leaders like Petsko appear to be afflicted with a form of schizophrenia: when writing as scientists, they are rational and moderate; but when confronted by ID or creationism, they erupt in a frenzy of wild assertions.
Frankensteins monster
The search for Frankenstein's monster is ever with us (Source here)

The propaganda charge relates to the film Expelled: No intelligence allowed. It seems to be of little concern to Petsko that the Discovery Institute is not responsible for this film. Knowledge that they have been positive about it is deemed sufficient to incriminate the organisation. Furthermore, Petsko points readers to Richard Dawkins' web site for a "spirited attack on the film" rather than summarising the substance of his charge of propaganda. The really disturbing thing is that there is no sense of outrage that academic freedom has been compromised in the treatment meted out to ID sympathisers. Instead of acknowledging that numerous research scientists have been given a very hard time by evolutionists, the message is implicit that they deserve all they get. Later, Petsko refers to teachers who want to teach creationism in a science class:

"What about the academic freedom argument? If someone wants to teach creationism in a science class, shouldn't they have the right to do so? Certainly - if they want to get fired. Because if they do that they deserve to get fired. It has nothing to do with academic freedom; it's about basic competence."

None of the people documented in Expelled set out to teach creationism. One was an editor of a journal who saw through the peer review process of an ID research paper before publishing it. Others were ID sympathisers whose ambitions to pursue research interests were thwarted by colleagues who insisted "It has nothing to do with academic freedom; it's about basic competence." In the UK, we have just witnessed the removal of Michael Reiss from his position as Education Director of the Royal Society because he did not buy into the dogmatic stance of secularised science demanded by his peers. He is an evolutionist, yet influential scientists deemed him guilty of incompetence. It is good to read some letters supportive of Michael Reiss in today's Independent:

"That a pressure group which appeared to have a limited grasp of the article could pillory a respected science educator to the point of resignation is a lasting disgrace" (Michael Poole),
and
"Michael Reiss is one of the most distinguished science educators we have, [. . .] I am simply surprised that the Royal Society is unable to understand the message that they are conveying to the public, that they are unable to defend and explain the simple argument that their director of education was proposing" (Professor David Waddington).

The second charge brought by Petsko relates to legislation and, in particular, the decision of the Louisiana House of Representatives to approve overwhelmingly a bill supporting academic freedom in teaching controversial issues in science. Possible areas of application were said to be evolutionary theory, the origins of life, global warming and human cloning. The pressure groups promoting evolutionary theory have repeatedly decried the idea that there is any controversy involved. Here is Petsko:

"Let me say this as clearly as possible, so there can be no mistake about what I mean: there is no controversy. Just because a few misguided so-called scientists question the validity of the concept of evolution doesn't mean there is a controversy. [. . .] The fact that some people believe nonsense does not give that nonsense scientific credibility. A challenge to existing scientific principles must be based on evidence, not on belief, and there isn't a shred of evidence to support either creationism or intelligent design. Those ideas belong in a religion or philosophy class, not in a science class."

It is sad to see these words repeated yet again. The Dissent from Darwin list was initiated to put to rest the claim that there was no dissent from Darwin coming from scientists. To call these people a "few misguided so-called scientists" tells us more about Petsko's grasp of the issues than anything else. The problem is that the evolutionary biology pressure groups cannot afford to have any critical scrutiny of their theories, because they know that many of their cherished dogmas are highly vulnerable. They have to insist that any discussion belongs outside science, because the dissenters actually appeal to evidence when they make their arguments! None of this, of course, is saying that we need to teach creationism or intelligent design in schools. The goal in science is to develop skills of critical thinking and reasoning from evidence. For previous posts on these issues, go here, here, here, here and here.

Petsko gave his message the title "It is alive". He likens the perceived threat to "Frankenstein's monster". He writes: "we must all arm ourselves with the one weapon we have that in the end the monster cannot overcome: the truth." There is some hope for a dialogue once it is realised that all those involved in education are committed to truth. ID scientists are not playing games: they are committed to truth - and they see the evidence of intelligent design through their research work. Creationists also are committed to truth. If we can break out of the stereotyped mental images of each other, there is perhaps a constructive way forward.

It is alive
Gregory A Petsko
Genome Biology 2008, 9:106 | doi:10.1186/gb-2008-9-6-106
Reprinted in ASBMB Today, pages 3-4 (August, 2008)

Abstract: We need to familiarize ourselves with the facts of evolution, so that we can mount a spirited defense against creationism and the forces of ignorance.

See also:

Luskin, C. NCSE Promotes Shrill Editorial Suggesting "Students be Forced to Consider the Possibility that There Is No God", Evolution News & Views, 15 September 2008

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09/17/08

Permalinkby 09:14:30 am, Categories: Literature - Articles, 1521 words   English (UK)

Michael Reiss and the science-religion issue

Professor Michael Reiss is a specialist in science education in the University of London who has been seconded to be the Royal Society's Director of Education. This latter post has been abruptly terminated because remarks made by Reiss were considered to have "led to damage to the Society's reputation". The Royal Society's Press Release is here. The controversy flared up at the same time as Reiss' refereed paper on these issues appeared in Studies in Science Education. We will briefly review aspects of that paper and why Reiss' views were considered outrageous by some senior Fellows of the Royal Society, including three Nobel Laureates.

The most significant aspect of Reiss' paper is the way he handles science. He presents several perspectives of science and considers the educational benefits of getting students to evaluate them.

"One approach that I have found to be of worth in science classes with undergraduates training to be science teachers is, when teaching about the nature of science, to get them to think about the relationship between scientific knowledge and religious knowledge. What seems to work well is to ask students, either on their own or in pairs, to illustrate this by means of a drawing and then for all of us in the class to discuss the various drawings that result. See, for example, the hypothetical representation in Figure 1. A person producing the representation in Figure 1 sees both religious and scientific knowledge as existing but envisages [. . .] no overlap between the two."

NOMA diagram
An alternative rendering of Reiss' Figure 1: The purported separation of religious knowledge and scientific knowledge (Source here)

This model is, of course, that popularised by Gould in his NOMA approach and often promoted by scientific societies wanting to reassure the public that science offers no threat to religious views. It is, however, not a consensus perception of the science-religion relationship. Reiss goes on to give 2 more figures (not reproduced here).

"However, there are many for whom scientific knowledge and religious knowledge are not distinct. At one end are those who draw religious knowledge as being much smaller than scientific knowledge and wholly or partly contained within it (Figure 2); at the other are those whose worldview is predominantly religious (Figure 3). Understandings of the relationship(s) between science and religion vary greatly, at least in part because of considerable variation in how people conceptualise both science and religion. The visual metaphor in Figures 1, 2 and 3 can be taken too far but it can serve as a useful heuristic device."

Reiss' view is that these different perceptions of science are very important for the teaching of issues where science and religious thinking addresses the same topics. These different models represent different paradigms about the world. Indeed, he uses the word "worldview" in this context. He writes: "The strongest argument, in my view, for teaching anything about religion in a science class, whether at school, college or university, is if it helps students better to understand science." This is a simple point, but Reiss has put his finger on the heart of the matter. There is no one "correct" perception of what science is! If the philosophy of science is steam-rollered into any of the above models, it leads to a breakdown of communication and there is no meaningful debate. Thus, those who have adopted a Figure 1 model (or, like Richard Dawkins, deny that religious knowledge even occupies a separate domain) will always treat religious knowledge as, at best, ascientific. They have no option but to say that design-based or creation-based approaches to origins lie outside science.

"Would one want explicitly to teach about creationism in science lessons? Both the knee-jerk and the considered reaction from most scientists and science educators has been 'no'. Here my interest is not in the legal situation that obtains in any one country [. . .] nor in the undoubted demands that teaching in this area can place on teachers but in whether it would be desirable on educational grounds to teach about creationism in science lessons. Given the preceding paragraph, I would not want any such teaching, were it to occur, to give the impression that creationism and the theory of evolution are equally valid scientifically. They are not (and nor is it appropriate to insist on spending equal amounts of time on evolution and creationism in science lessons).
"However, I do not belong to the camp that argues that creationism is necessarily nonscientific. For all that I have no doubt that the overwhelming majority of those who believe in creationism (and intelligent design theory) do so because of their religious beliefs it is logically possible to hold that evolution (sensu major anatomical, physiological, genetic and biochemical changes in organisms over long periods of time) has not happened."

Although Reiss writes as one satisfied with the validity of evolutionary theory, he recognises that it is possible for people with alternative worldviews to interpret the data differently. The relatively high proportion of young people entering schools and colleges with these alternative worldviews makes it imperative to bring issues of creation and design into science education. In his long paper, Reiss covers many other points than those reviewed here. From his conclusion:

"I have examined here the nature of the issue both in general terms and with reference to particular topics. I have argued that there are good reasons for students being introduced to aspects of the science/religion issue in science lessons. Such teaching is not easy, but done well it can be respectful of students, motivating and fulfilling for them and help them to learn more about the nature and content of science."

Michael Reiss' arguments are modest and rational. Although he is aware that others take a different view, he has set out, in good faith, his reasons for introducing discussions of creation and intelligent design in science education. The Times reports some of the reaction thus:

His resignation comes after a campaign by senior Royal Society Fellows who were angered by Professor Reiss's suggestion that science teachers should treat creationist beliefs "not as a misconception but as a world view". Sir Richard Roberts, who won the Nobel Prize for Medicine in 1993, described such views as outrageous, and organised a letter to the society's president, Lord Rees of Ludlow, demanding that Professor Reiss be sacked. Phil Willis MP, the chairman of the Commons Innovation, Universities, Science and Skills Committee, was due to meet Royal Society officers today to demand an explanation of Professor Reiss's comments."

To his credit, Richard Dawkins was prepared to differ from his colleagues: "To call for his resignation on those grounds, as several Nobel-prize-winning Fellows are now doing, comes a little too close to a witch-hunt for my squeamish taste." The influential Lord Winston was also unable to support the call for Reiss to be sacked:

Reacting to his stepping down, Lord Robert Winston, professor of science and society at Imperial College London, said: "I fear that in this action the Royal Society may have only diminished itself. This is not a good day for the reputation of science or scientists. This individual was arguing that we should engage with and address public misconceptions about science - something that the Royal Society should applaud." (Source: BBC News)

There are many who have dismissed the documentary Expelled as worthless, but its witness to discrimination within the academic world is of great importance. Now we find another casualty - someone who is a supporter of evolution but who dared to step outside the boundaries set by the self-appointed gatekeepers of modern secular science. When will these people be called to account?

Robert Matthews has a powerful conclusion to his blog:

"The motto of Royal Society is 'Nullius in verba' - roughly speaking, take no-one's word for it. Its treatment of Reiss suggests that when it comes to words of dissent, the attitude of the Royal Society is closer to that of a madrassa than a learned body."

Should science educators deal with the science/religion issue?
Michael J. Reiss
Studies in Science Education, 44(2), September 2008, 157 - 186 | DOI: 10.1080/03057260802264214

Abstract: I begin by examining the natures of science and religion before looking at the ways in which they relate to one another. I then look at a number of case studies that centre on the relationships between science and religion, including attempts to find mechanisms for divine action in quantum theory and chaos theory, creationism, genetic engineering and the writings of Richard Dawkins. Finally, I consider some of the pedagogical issues that would need to be considered if the science/religion issue is to be addressed in the classroom. I conclude that there are increasing arguments in favour of science educators teaching about the science/religion issue. The principal reason for this is to help students better to learn science. However, such teaching makes greater demands on science educators than has generally been the case. Certain of these demands are identified and some specific suggestions are made as to how a science educator might deal with the science/religion issue.

See also:

Matthews, R. Royal Society or Rotten Society? (First Post, September 17, 2008)

Reiss, M. Science lessons should tackle creationism and intelligent design, (Guardian Science Blog, September 11 2008)

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09/12/08

Permalinkby 10:22:09 am, Categories: Literature - Articles, 811 words   English (UK)

Hairless Dogs as an example of deleterious mutations

It is widely recognised that dogs provide a fine example of one species (a domesticated wolf) whose different breeds exhibit very large variations in morphology. Some of these variants have a genetic origin, and the details of one of these traits (hairlessness) have recently been clarified.

"The American Kennel Club lists three breeds of hairless dogs: the Chinese crested; [. . .] the Mexican hairless dog; and the Peruvian Inca Orchid dog. These canines typically live a normal life span, though they lack the full set of 42 teeth common to other adult dogs. Researchers have long known that a dominant gene causes this set of abnormalities, called canine ectodermal dysplasia (CED). That means dogs need only inherit one copy of it to be bald; with this particular gene, two copies are lethal. But the gene itself remained a mystery."

Hairless and coated dogs
Chinese crested dogs: hairless and coated. Graphic here (Tosso Leeb)

It is a mystery no longer, thanks to some detective work by a team of scientists led by Tosso Leeb, a veterinary geneticist at the University of Bern, Switzerland. According to one writeup, "Because Chinese crested dogs have been inbred for decades, the genomes of any two dogs are nearly identical, and slight variations are very apparent." So the researchers compared the genomes of hairless animals with those of "powderpuffs" - the same breed but with more normal hair.

"The technique, called genomewide association mapping, turned up a suspicious-looking region on chromosome 17. To investigate further, Leeb and his team collected additional DNA samples from a wider array of hairless and coated dogs. In all, they looked at 93 hairless and 49 coated Chinese crested dogs, 39 hairless and six coated Peruvian hairless dogs, and eight Mexican hairless dogs (there is no coated counterpart). Mapping the chromosome 17 sequences revealed an insertion of seven letters, or base pairs, of genetic code in a gene called FOXI3 in all of the hairless dogs. Although the exact function of the FOXI3 gene is unknown, other genes in the FOX family control embryonic development in mammals."

FOXI3 appears to function as a switch, with the mutation knocking out the normal development of parts of the unfortunate animal. "Leeb says the mutation most likely interferes with the genetic instructions for hair and teeth proteins, causing CED in dogs." There is particular interest because of the possible implications for humans:

"As it turns out, the human genome sequence that scientists use as a gold standard for deciphering genetic information contained a mistake in the FOXI3 gene, making it impossible for computer programs to find it. Another human sequence contains the correct information, confirming the existence of FOXI3 in people, as well as in mice and dogs, Leeb says."

Apparently, the team are currently engineering the FOXI3 mutation in mice, to find out more. The expectation is that the mutation will have comparable effects in mice, dogs and humans. One commentator suggested this could be a "starting point for research on new baldness remedies in humans".

So, the nature of this mutation is that it is a degeneration of the genome. There is no new information, but rather a loss leading to decreased functionality. These mutants are kept alive by mankind, whether they be Aztecs who considered them sacred nearly 4000 years ago, or whether they be proud owners who are prepared to pay $1000 for the experience of having one as a pet. Outside these environments, they would soon die. The take-home message is that these dogs are witnesses to the largely negative impact of mutations on living things. Darwinists have a hard task when they set out to convince the world that the rare occasional mutation is responsible for building complexity. We are rather short of any good examples of this.

Past winner of the worlds ugliest dog award
This poor little rascal knows what it's like to have part of his genome deleted (Source here)

A Mutation in Hairless Dogs Implicates FOXI3 in Ectodermal Development
Cord Drogemuller, Elinor K. Karlsson, Marjo K. Hytonen, Michele Perloski, Gaudenz Dolf, Kirsi Sainio, Hannes Lohi, Kerstin Lindblad-Toh, and Tosso Leeb.
Science 321, 12 September 2008: 1462.

Abstract: Mexican and Peruvian hairless dogs and Chinese crested dogs are characterized by missing hair and teeth, a phenotype termed canine ectodermal dysplasia (CED). CED is inherited as a monogenic autosomal semidominant trait. With genomewide association analysis we mapped the CED mutation to a 102-kilo-base pair interval on chromosome 17. The associated interval contains a previously uncharacterized member of the forkhead box transcription factor family (FOXI3), which is specifically expressed in developing hair and teeth. Mutation analysis revealed a frameshift mutation within the FOXI3 coding sequence in hairless dogs. Thus, we have identified FOXI3 as a regulator of ectodermal development.

See also:

Callaway, E., When being bald and ugly is the lesser of two evils, (New Scientist, 11 September 2008)

Saey, T.H. A 'foxi' gene for dog baldness, (Science News: Thursday, September 11th, 2008)

Zelkowitz, R. How Much Is That Baldie in the Window? (ScienceNOW Daily News, 11 September 2008)

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09/11/08

Permalinkby 11:52:34 am, Categories: Literature - Articles, 746 words   English (UK)

A call for an end to Pseudo-Darwinian hype

Austin Hughes does not mince his words in describing a "major hindrance to progress" in understanding the evolutionary past. He claims that a major factor has been "confusion regarding the role of positive (Darwinian) selection". This addresses some fundamental issues in evolutionary biology because, for many, any evidence of adaptation is automatically interpreted as natural selection favouring adaptive mutations. But yes, just in case you think Hughes might qualify his charge elsewhere, read on and find that he makes it even more explicit!

"To biologists schooled in Neo-Darwinian thought processes, it is virtually axiomatic that any adaptive change must have been fixed as a result of natural selection. But it is important to remember that reality can be more complicated than simplistic textbook scenarios."

Textbook simplicity
"If you have variation, differential reproduction, and heredity, you will have evolution by natural selection as an outcome. It is as simple as that." (Source here)

The problem is not one that can be easily corrected, because it is endemic. According to Hughes: "Thousands of papers are published every year claiming evidence of adaptive evolution on the basis of computational analyses alone, with no evidence whatsoever regarding the phenotypic effects of allegedly adaptive mutations." The researchers have adopted a mindset which blinds them to alternative approaches to handling the data. The problem relates to codon-based methods of testing for positive selection. We do not need here to go over the theory behind these methods, nor follow how Hughes arrives at the view that there has been an "unwarranted generalization" from one case to all cases. However, we can note this conclusion:

"Yet, despite their shaky foundations, numerous publications have used these methods as the basis for claims of positive selection at the molecular level."

The trigger for the alarm bells sounding is a paper by Yokoyama et al (blogged here). Hughes sees this paper as a model of its kind, establishing the genetic basis for variation and devising tests for positive selection which allow conventional thinking to be scrutinized.

"It is to be hoped that the work of Yokoyama et al. will help put an end to these distressing tendencies. By incorporating experimental evidence regarding the phenotypic effects of reconstructed evolutionary changes, this study sets a new standard for studies of adaptive evolution at the molecular level."

The take-home message is that (bad) theory has dominated empirical analysis for too long in evolutionary biology. It is time to put things in order. We need less reliance on the deductive framework provided by neo-Darwinism, and more attention to empiricism and induction. (For a previous blog related to this, go here). Hughes calls for a new standard in research:

"In recent years the literature of evolutionary biology has been glutted with extravagant claims of positive selection on the basis of computational analyses alone, including both codon-based methods and other questionable methods such as the McDonald-Kreitman test. This vast outpouring of pseudo-Darwinian hype has been genuinely harmful to the credibility of evolutionary biology as a science."

With these thoughts in mind, it may be worth revisiting topics (here, here and here) that have been discussed previously: drawing attention to the way theory dominates the interpretations placed on data, and how researchers are curiously blind to alternative approaches to handling the same data. This is Kuhnian "normal" science. It preserves the paradigm - but at what cost?

The origin of adaptive phenotypes
Hughes, Austin L.
Proceedings of the National Academy of Sciences, 105(36), 13193-13194, September 9, 2008 | doi: 10.1073/pnas.0807440105.

First Paragraph: Sequences of DNA provide documentary evidence of the evolutionary past undreamed of by pioneers such as Darwin and Wallace, but their potential as sources of evolutionary information is still far from being realized. A major hindrance to progress has been confusion regarding the role of positive (Darwinian) selection, i.e., natural selection favoring adaptive mutations. In particular, problems have arisen from the widespread use of certain poorly conceived statistical methods to test for positive selection. Thousands of papers are published every year claiming evidence of adaptive evolution on the basis of computational analyses alone, with no evidence whatsoever regarding the phenotypic effects of allegedly adaptive mutations. But it would be a mistake to dismiss Yokoyama et al.'s study, in this issue of PNAS, of the evolution of visual pigments in vertebrates as more of the same. For, unlike all too many recent papers in the field, this study is solidly grounded in biology.

See also:

Coppedge, D.F. How Not to Prove Positive Selection (Creation-Evolution Headlines, Sept 5, 2008).

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09/10/08

Permalinkby 04:20:42 pm, Categories: Literature - Articles, 810 words   English (UK)

Adaptations affecting dim-light vision in vertebrates

An important paper has appeared recently on the way organisms have adapted their vision to dim light. The authors point out that the first vertebrates appearing in the fossil record lived in shallow water, open shelf marine environments. Many animals living in these environments today have rhodopsin molecules with their greatest sensitivity to light of about 500 nm, which matches what we know of spectral intensities at dusk. This, then, becomes the baseline figure for light sensitivity, and the authors have identified other maximum sensitivities ([lambda]max) that are representative of animals from different ecological niches.

"According to their [lambda]maxs and light environments, rhodopsins are classified into four groups: deep-sea (480-485 nm), intermediate (490-495 nm), surface (500-507 nm), and red-shifted (525 nm) rhodopsins."

Rhodopsin molecule
Rhodopsin, a dim-light photoreceptor (Source here)

A major achievement of the research is the identification of modification to rhodopsins that have contributed to wavelength sensitivity. "[T]he [lambda]maxs of most contemporary rhodopsins can be explained largely by a total of 15 amino acid replacements at 12 sites." The authors could, like many others have done, assume that these 15 amino acid changes are the result of positive (Darwinian) selection. However, they did not make this assumption but set out to test for positive selection using various methods. This is where there were some unexpected findings. The surprises are well expressed by Hughes in a commentary essay:

"In fact, the results showed that the codon-based methods were 100% off target. When Bayesian methods were applied to a set of closely related rhodopsin sequences, eight sites were identified as "positively selected." Yet not one of these sites was among the 12 sites known to be involved in adaptive changes in rhodopsin sensitivity. Moreover, amino acid changes at these sites were shown experimentally to have no effect on [lambda]max and thus almost certainly to lack any adaptive significance."

This is a remarkable finding. Adaptation has occurred, but evidence of positive (Darwinian) selection lacks confirmation. At very least, it demonstrates that the Darwinian mechanism of survival of the fittest is not the key to understanding adaptation of dim-light vision. As we shall see (in a separate blog), Hughes goes much further than that.

It is worth noting that the phenotypic adaptations analysed in this research would be regarded as microevolution by many scientists. We are not considering variations needed to form new functionality, but rather the fine-tuning of existing functionality. As such, these findings are no more supportive of evolutionary biology than they are of ID biology or even Creation-orientated biology. However, since the research demonstrates adaptation without positive selection, is this evidence for neutral evolution? Serious questions about this can be raised because of convergence:

"4 of the 15 critical amino acid replacements occurred multiple times during rhodopsin evolution: [. . .]. Such extensive parallel changes strongly implicate the importance of these and other amino acid replacements at the 12 sites in the functional adaptation of vertebrate dim-light vision." [. . .] "In vertebrate rhodopsins, several amino acid replacements occurred multiple times and, furthermore, the biologically significant [lambda]max shifts occurred on at least 18 separate occasions."

This points us away from stochastic processes towards something more structural. In turn, this raises the question whether mechanisms for variation are designed rather than deterministic or stochastic. But this question cannot even be considered by those who reject design on ideological grounds. Here is yet another example of where design perspectives open up novel aspects of research to explain data that does not fit comfortably into the reigning paradigm.

Elucidation of phenotypic adaptations: Molecular analyses of dim-light vision proteins in vertebrates
Shozo Yokoyama, Takashi Tada, Huan Zhang, and Lyle Britt
Proceedings of the National Academy of Sciences, 105(36), 13480-13485, September 9, 2008 | doi:10.1073/pnas.0802426105.

Vertebrate ancestors appeared in a uniform, shallow water environment, but modern species flourish in highly variable niches. A striking array of phenotypes exhibited by contemporary animals is assumed to have evolved by accumulating a series of selectively advantageous mutations. However, the experimental test of such adaptive events at the molecular level is remarkably difficult. One testable phenotype, dim-light vision, is mediated by rhodopsins. Here, we engineered 11 ancestral rhodopsins and show that those in early ancestors absorbed light maximally ([lambda]max) at 500 nm, from which contemporary rhodopsins with variable [lambda]maxs of 480-525 nm evolved on at least 18 separate occasions. These highly environment-specific adaptations seem to have occurred largely by amino acid replacements at 12 sites, and most of those at the remaining 191 (~94%) sites have undergone neutral evolution. The comparison between these results and those inferred by commonly-used parsimony and Bayesian methods demonstrates that statistical tests of positive selection can be misleading without experimental support and that the molecular basis of spectral tuning in rhodopsins should be elucidated by mutagenesis analyses using ancestral pigments.

See also:

Hughes, A.L. The origin of adaptive phenotypes, Proceedings of the National Academy of Sciences, 105(36), 13193-13194, September 9, 2008 | doi: 10.1073/pnas.0807440105.

Coppedge, D.F. How Not to Prove Positive Selection (Creation-Evolution Headlines, Sept 5, 2008).

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09/07/08

Permalinkby 03:26:15 pm, Categories: Literature - Articles, 817 words   English (UK)

The formidable problem of assembling the bacterial flagellum

The iconic status of the bacterial flagellum for ID is easily justified, even though there are numerous other structures with complexities that are similarly astounding. In view of its potential for applications in nano-machines, the flagellum has been much studied and research shows no signs of abating.

Bacterial flagellum
The bacterial flagellum (source here)

Interest is not just in the mechanisms of providing torque and the way this is transmitted to the propeller. The researchers are intensely interested in the assembly of the flagellum. A recent review article declares that the assembly of this structure "poses the formidable problem of coupling temporal gene expression to specific stages of the organelle-assembly process".

"To function properly, each component of the final molecular machine that assembles by protein polymerisation must achieve an accurate size and subunit composition. Coordination of this assembly process is aided by gene regulatory mechanisms that manage the logistics of component production, whereas other mechanisms regulate the timing of the specific subunits that are being exported.
[. . .]
"Many regulatory checkpoint mechanisms of flagellum assembly have been elucidated, and these present a sophisticated strategy for coordinating gene expression to the assembly process."

As a review, this article presents a helpful overview of thinking about the assembly process. ID advocates also affirm assembly via natural processes - the intelligent agency is located in the design of the structure and the orchestration of the assembly process. However, the concluding paragraph of this paper introduces new ideas that are not discussed earlier:

"Finally, it seems that the bacterial flagellum is a structure of great complexity. In an attempt to understand why, it is not necessary to resort to intelligent designers, because surely a designer would have fashioned a simpler structure and gene regulation system. We only need to be reminded that evolution demands that changes occur on the existing structure - no starting from scratch. It is fair to say that we are at long last making a dent in our understanding of how this evolutionary process might have occurred for the reducibly complex bacterial flagellum and the beautiful result it has produced."

What is the argument here? It seems to be that the bacterial flagellum and its gene regulation system is too complex to have been fashioned by an intelligent designer! "Surely", affirm the authors, a designer would have gone for something simpler. Perhaps we should congratulate them for devising a novel argument against ID. Normally, we are caricatured as saying 'things are too complicated to have arisen by natural processes', but this argument suggests that the flagellum is too complicated even to have been the result of intelligent agency!

We could be more sympathetic to this reasoning if the authors could identify that part of the spectrum of complexity where the ID argument is justified. However, what we have here is a 'no-win' situation for ID. Furthermore, the reasoning is based on false premises. ID advocates base their design inferences on the recognition of complex specified information, not on "complexity" per se. The issue is not whether the structure is "of great complexity" but whether it exhibits complex specified information. Researchers need to assess whether the phenomenon under investigation could have arisen by the tinkering process of evolutionary transformation or whether it bears the marks of an exquisitely engineered artefact. Since the authors refer to the bacterial flagellum as "a beautiful result", it is not unreasonable to rule out incremental botching. (For more on this, go here). This suggests the burden of proof here rests on those who defend tinkering rather than intelligent agency.

My final comment here is to ask the question why this paragraph is deemed relevant to the subject matter of the review. It does not emerge from the data or the analysis. The word "surely" is lacking in content, appealing to gut feeling rather than evidence. Like so many academic contributions about structures exhibiting complex specified information, the evolutionary anchor is spin rather than substance. If reasoning like this is deemed acceptable in an academic paper, there should be no question of the legitimacy within science forums of arguing the case for intelligent agency.

Coordinating assembly of a bacterial macromolecular machine
Chevance, F.F.V., and Hughes, K.T.
Nature Reviews Microbiology, 6, 455-465, (June 2008)

The assembly of large and complex organelles, such as the bacterial flagellum, poses the formidable problem of coupling temporal gene expression to specific stages of the organelle-assembly process. The discovery that levels of the bacterial flagellar regulatory protein FlgM are controlled by its secretion from the cell in response to the completion of an intermediate flagellar structure (the hook-basal body) was only the first of several discoveries of unique mechanisms that coordinate flagellar gene expression with assembly. In this Review, we discuss this mechanism, together with others that also coordinate gene regulation and flagellar assembly in Gram-negative bacteria.

See also:

Coppedge, D.F. Cellular Machines Work Like Cameras, Winches and Turboprops, (Creation-Evolution Headlines, 3 September 2008)

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09/05/08

Permalinkby 08:41:57 am, Categories: Literature - Articles, 625 words   English (UK)

Quote- Atheism could be science's contribution to religion

Nature's editorial linked to the work of the Templeton Foundation (blogged here) has stimulated a response from two scientists who think that only scientists can make truth claims about the world around us. Adherents of religions, in their view, have no business encroaching into this territory. The authors identify a "fundamental conflict" which "can never be reconciled until all religions cease making claims about the nature of reality".

Truth claims
Who can make claims with integrity about the nature of reality?
(Graphic source here)

In their view, religions should be the subjects of scientific enquiry. This is necessary to deconstruct the socially-constructed nature of religious systems.

"The scientific study of religion is indeed full of big questions that need to be addressed, such as why belief in religion is negatively correlated with an acceptance of evolution. One could consider psychological studies of why humans are superstitious and believe impossible things, and comparative sociological studies of religion using materialist explanations of the rise and fall of the world's belief systems."

Cobb and Coyne are in no doubt about the findings (but for a related blog, go here). They distance themselves from the approach adopted by Nature's Editors:

"The outcome of such work, we predict, will not bring science and religion (or 'spirituality') any closer to one another. You suggest that science may bring about "advances in theological thinking". In reality, the only contribution that science can make to the ideas of religion is atheism."

Three points are worthy of note about this correspondence. The first is the complete absence of any historical perspective. There is no acknowledgement that Science emerged from a Christian culture, and that many of science's fundamental concepts are underpinned by Christian theology. Most of the early scientists were Christians, and regarded scientific work as their calling before God. (For more on this, go here).

The second point is the apparent inability of Cobb and Coyne to distinguish between "religion" and underpinning philosophies. This means that they lapse into yet another tired old polemic to set up "science" against "religion". We expect more discernment and substance from intellectual leaders. These matters are well-documented by Christian philosophers of science and ought to be known to anyone wanting to engage in constructive debate over these issues.

Thirdly, Cobb and Coyne confuse cause and effect when the say: "the only contribution that science can make to the ideas of religion is atheism." From the Enlightenment onwards, there has been a secularising trend in science. This is not inherent to science, but it reflects cultural trends among the intelligentsia. This trend is apparent today in the way atheistic scientists redefine science to suit their own philosophy. They write: "Surely science is about finding material explanations of the world". This definition presupposes that "the world" is entirely material and that it can be explained wholly in terms of natural causes. However, to presuppose this is not to prove the point! To presuppose it actually closes up avenues of enquiry that might conceivably lead to design inferences being made, thereby revealing that any explanation of the real world that does not incorporate intelligent causation must be deficient. In terms of methodology, Cobb and Coyne are undermining the integrity of science - to be open to evidence wherever it leads. What they should be recognising is that atheism emerges from a mutant science that has first presumed atheism.

Atheism could be science's contribution to religion
Matthew Cobb and Jerry Coyne
Nature 454, 253-254 (28 August 2008) | doi:10.1038/4541049d

First paragraph: We were perplexed by your Editorial on the work of the Templeton Foundation ('Templeton's legacy' Nature 454, 253-254; 2008). Surely science is about finding material explanations of the world - explanations that can inspire those spooky feelings of awe, wonder and reverence in the hyper-evolved human brain.

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08/10/08

Permalinkby 11:48:23 am, Categories: Literature - Books, 1517 words   English (UK)

The Darwingate Papers

Here's some gripping reading for your summer vacation!

Book cover
The Darwin Conspiracy by Roy Davies (2008)

This publication marks the 150th anniversary of the joint presentation of Darwin and Wallace of their thinking about evolution by natural selection to the Linnean Society. The book is a blockbuster because it claims that "Darwin perpetuated one of the greatest crimes in the history of science". It concludes that Darwin plagiarised Alfred Russel Wallace, deceived the world about the maturity of his own ideas before 1858, and, to satisfy his personal need for glory, failed to give credit to scholars who influenced his thinking.

It needs someone with remarkable abilities to put together such a radical revision of history. The author's experience is in writing, producing and directing documentaries that challenge popular historical narratives. During the 1980s, he was responsible for a TV programme about Darwin that presented a story that was and is widely accepted:

"Darwin [was] a nervous man who concealed the secret of how species originate for more than twenty years, until he was forced to publish when he realised someone else might get there before him. The programme was called The Devil's Chaplain."

Since that time, Davies has come to reject this account as iconic.

"Today, having researched the Darwin record for myself and having been utterly convinced by what I have learned, I believe [. . .] that the original programme (which went out under my name) left a great deal of new information about Darwin unmentioned. If I had known then what I know now, The Devil's Chaplain would never have been made. What you are about to read is the story leading up to the discovery of the origin of species, which I would eagerly have transmitted in its place."

Being a natural sceptic of conspiracy theories, I read this book cautiously - 'convince me if you can!' By the end, I was persuaded. What impressed me was the way Davies drew on the research of numerous Darwin scholars, showing that although they discovered important aspects of Darwin's life and work, they were unable to package their findings into a coherent whole. The person who came closest was Arnold Brackman, who concluded in 1980 that Darwin did plagiarise Wallace. It is the 'big picture' that Davies provides for the first time, and my title makes reference to the earlier eye-opening research papers.

The first researcher to be discussed in the book is Professor Darlington of Oxford University. He sought an answer to the question "by what thought process had Charles Darwin actually arrived at his ideas about evolution?".

"Darlington pointed out that he could not find, in all the accounts of Darwin's work published up to that time, any suggestion that some original germ in Darwin's mind had led inexorably to the full development and enunciation of this big idea."

Darlington recognised that Darwin's writings bore the marks of rhetoric. For example, "Darwin's unawareness of what his contemporaries were thinking matched his unawareness of what his predecessors had written". This comment is highly significant for what comes later, because Darwin was very concerned about gaining precedence for his own ideas and he consistently referred to "my theory".

The second scholar is the anthropologist Loren Eiseley. He identified a mismatch between the time (October 1838) when Darwin read Thomas Malthus's Essay on Population (which Darwin claimed "Here then I had at last got a theory by which to work. . .") and yet 18 months earlier he was already making notes on the very same ideas? After noting many similarities between the way Edward Blyth reported data in his published articles and the wording in Darwin's notebook about these same phenomena, Eiseley came to the conclusion that Darwin had lifted Blyth's thinking about natural selection - without acknowledgement.

"Eiseley believed, even making some allowance for the accidental use of the same sources, that the effect of his research was cumulative. He argued that these many similarities could not be explained by chance and that Darwin had plundered Blyth's articles for the ideas which underpinned the thinking that led to On the Origin of Species."

Barbara Beddall set out to refute Eiseley's suggestion that Darwin had plagiarised Blyth. She particularly wanted to find the letters between Wallace and Darwin - but found that some were missing. She also found, in the period 1853-8, that other letters to Lyell, to Hooker and to Asa Gray were lost. This, in her opinion, was "very odd". She came to the conclusion that they had been deliberately destroyed to obscure the record of how Darwin formulated his theory. She commented: "Without these letters, a clear idea of the extent of Wallace's influence on Darwin is beyond academic assessment and the full story impossible to gauge". But the jigsaw that Davies has assembled does have a clearer picture so that the significance of the missing letters is not "odd" but part of a pattern.

"The idea that it might have been Darwin himself [who destroyed the letters] seems not to have occurred to her."

Altogether, Davies features the work of nine researchers, with each contributing one or more pieces to the jigsaw. This review cannot do justice to the way the arguments develop. Here is just one more nugget. It concerns another letter of Wallace dated 2 March 1858. We know it was posted at the same time as his momentous letter to Darwin that contained the short paper that was presented at the Linnaean meeting in on 1st July that same year. Darwin claimed the letter reached him on 18 June, the same day that he wrote to Lyell to say that Wallace could not have written a better abstract for Darwin's own work. However, as Davies shows, we now have a complete timeline for the transport of this letter from the Dutch East Indies to its arrival in the UK, and the date-stamped envelope of the other letter posted along with the letter to Darwin. These date stamps show that the letter arrived in the UK on 2 June - on course for delivery to the addressee on the following day. Davies writes: "

The arrival of Wallace's letter on 3 June would have given Darwin more than enough time to digest its contents and make the two lengthy changes to the "natural selection" chapter of his manuscript. It would also have allowed him to claim that Wallace's ideas were replicas of his own."

Most people coming across this for the first time will be incredulous, thinking that Darwin's ideas on evolution by natural selection before this time were well documented. Davies shows that this is erroneous. This is why his 'big picture' is so important: Darwin was like a man groping in the dark. He gathered data, hoping to find a synthesis, but theoretical ideas were elusive. When he came across other people's ideas that helped to make sense of the data, he gathered them as well, treating them as his own. The plagiarism of Wallace was not an isolated incident, but part of a pattern of behaviour.

There are really two conspiracies in this book. Lyell and Hooker played a significant role (not in plagiarising, but in engineering circumstances to favour their gentleman friend).

"The members [of the Linnean Society] agreed that Darwin and Wallace should be acknowledged as co-discoverers of the theory of how species evolve, which would henceforth be known as the Darwin-Wallace theory of evolution. The crucial question of priority was settled by placing Darwin's name before Wallace's. Lyell and Hooker had successfully conspired to hand Charles Darwin the proze he had coveted for more than twenty years."

Wallace
Alfred Russel Wallace in Singapore in 1862 (Source here)

Wallace emerges as the real hero. He could easily be made a role model for young scientists. Davies refers to him as a "brilliant yet unassuming naturalist who was never to comprehend the full extent of the conspiracy enacted against him".

Clearly, if Davies' argument is correct, the iconic Darwin needs to be dethroned. When this is accomplished, we will be in a better position to reappraise his significance as a scientist. In the meantime, here is a summary paragraph from Davies:
"Charles Darwin was a very secretive man with a driving ambition. He neither praised nor tipped his hat in the direction of Jean-Baptiste Lamark or of his grandfather Erasmus. He never openly acknowledged his debt to Edward Blyth, nor to Patrick Matthew (who had been one of the first to write about the 'natural means of selection', a phrase that Darwin modified and used without attribution). He never acknowledged his debt to Wallace. By the time Eiseley, Gruber, Beddall, McKinney, Brackman and Brooks began reassembling the long-lost pieces of the jigsaw, the myth-making surrounding Darwin's achievement, which had so worried Darlington in 1959, was complete."

Book Reviewed:
The Darwin Conspiracy - Origins of a Scientific Crime, by Roy Davies, Golden Square Books. May 2008.

Links:

The Darwin Conspiracy Home page

Tyler, D, Charles Darwin - Icon of Evolution, ARN Literature Blog, 30 June 2008

Tyler, D., Why Alfred Russel Wallace deserves to be remembered,ARN Literature Blog, 11 March 2008

Flannery, M. Science or Monkey Business?: A Review of Roy Davies' The Darwin Conspiracy, Uncommon Descent, 1 August 2008

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