This is a repost of something which was lost in the server move...

In The Family That Couldn't Sleep, D.T. Max states that

Prion diseases are a fascinating medical mystery because they appear to be the only disease that takes on those three forms: genetic, infectious, and accidental ("sporadic").^[1]

What a bizarre thing to say. Bizarre in part because prion "diseases", as the plural suggest, is a category of diseases rather than a single disease, and there is a near infinite set of categories that one could devise for diseases, based on molecular, cellular, genetic, physiological, anatomical, epidemiological and clinical variables. A great many of these categories will, of course, include individual diseases of each form. Max surely knows this: he himself introduces another disease category in the book -- Transmissible Spongiform Encephalopathies (TSEs). The TSE category overlaps with the prion disease category, but, as the name suggests, the TSEs are transmissible.

But bizarre, mostly, because the lack of truth in the statement stares one in the face.

The obvious example here is the disease category "cancer". We could call them "cell-cycle regulator diseases" if we wanted to illustrate that this category is based on similar molecular level criteria as prion diseases are. Cancers are clearly hereditary, familial ("genetic" is too simplistic^[2]), and sporadic. But they can also fit into the "infectious" category, either in the form of viral oncogenesis (e.g. with HPV, famous for its role in cervical cancers), or in fully transmissible cancers, of which there are two known examples. One of these, Devil Facial Tumour Disease, was blogged about here.

But, to complicate things further, most instances of cancer can not even be neatly filed as genetic, sporadic, or transmissible. Indeed, few disease aetiologies can be pinned down so precisely. Rather, for every disease, a number of variables are interacting and playing a role. The cancer may have a familial trend, but it would not have occurred had the individual led a different lifestyle. You may live with HPV, but be deficient in the other variables that are required for cancer development. The Tasmanian Devil may even have a chance mutation in its major histocompatibility complex (the set of genes which raise flags to the immune system to inform it that the cell is a friendly one which should not be destroyed) which allows the immune system to recognise and combat the transmissible tumour.

Max is aware of this fact too, but I think he fails to pick up on its importance. In the book, he mentions that the incidence of variant CJD (the novel human prion disease thought to be caused by eating beef containing BSE prions) rose from three in 1995 to 27 in 2000, and then began falling again.^[3] Rather than the numbers growing rapidly and continuously for many years, as initially projected, there were only a small number of deaths relative to the population of British meat-eaters. The reason? Most of those who died carried mutations which pre-disposed them to developing vCJD (the beef simply tipped them over the edge).^[4] Of course, a vCJD epidemic has not yet been ruled out -- perhaps those who are not so pre-disposed merely have longer incubation times for the disease. If this turns out to be the case, how should be categorise vCJD? As a single disease caused by contaminated beef, or as two different diseases, classified according to genetics? Either way, to call it (and other "transmissible spongiform encephalopathies") transmissible, is an oversimplification.

Why do I labour this point so? Because I think it is another example of faulty "nature versus nurture" thinking: this prion disease is genetic; that prion disease was caused by contaminated food. There's just no need to categorise everything as one-or-the-other.

References

1. ^   D.T. Max, 2006. The Family That Couldn't Sleep: A Medical Mystery. Random House.
2. ^  There is an introduction to the differences here.
3. ^  Azra C Ghani, Christl A Donnelly, Neil M Ferguson and Roy M Anderson: Updated projections of future vCJD deaths in the UK. BMC Infectious Diseases 2003, 3:4 doi
4. ^  e.g. Cathepsin D -- Matthew T Bishop, Gabor G Kovacs, Pascual Sanchez-Juan and Richard SG Knight: Cathepsin D SNP associated with increased risk of variant Creutzfeldt-Jakob disease. BMC Medical Genetics 2008, 9:31 doi

The psychologist Oliver James was on The Late Edition a couple of weeks ago.^[1] His argument was unconvincing and his behaviour unimpressive. So I took a quick look at his website. He offers for download a Radio 3 Nightwaves debate on "nature versus nurture" with James, Steven Pinker, Hilary Rose and John Gray from 2002. Always at the cutting edge, I thought I'd take a listen.

What an utter waste of airtime.^[2] Anybody who knows a good chunk of background on the subject would just have heard some people sitting around having an over-the-top argument over trivial matters. But if you don't know the background, you could very easily get the impression that the argument was over something fundamental — especially considering all of the appeals to consequences that were flying back-and-forth. One camp arguing fiercely for nature and the other arguing fiercely for nurture. The root of the problem? Nobody thought to explain that they were arguing about the cause of variation in behaviour, not the cause of the behaviours themselves. Nobody ever seems to do that when discussing "nature versus nurture," yet these four academics must be aware of the difference, and how misleading it is to conflate them. Pinker stated that genetic determinism is a myth, while Rose pointed out that nobody has believed in the "blank slate" for a century. But this was as close as they got to acknowledging the true nature of development. I know that Pinker did eventually make the point in The Blank Slate, the book he was promoting at the time of the debate, but it was buried somewhere near the end.

Perhaps if every discussion of the topic came with some sort of disclaimer, or started with a basic introduction, a lot of misunderstanding and unnecessary shouting would be avoided. Here's my proposal for it: there is no nature versus nurture problem. All traits — physical and behavioural — require a certain set of genetic and environmental conditions. All characteristics have many diverse and variable influences. All personality quirks, preferences, and even diseases require just the right nature and nurture in order to develop. Even when things go wrong, our biology is contributing something: if (contracted(disease)) die;.

When people argue over nature and nurture, the argument is over which is behind any between-individual (or between-population) variation in the trait in question. Sometimes we can agree that one-or-other factors is trivial — the death certificate of a traffic-accident victim will never list "lack of hard-exoskeleton" as cause-of-death — because there is no significant or relevant variation in it. But in more cases than you might imagine, it is important to consider both sets of conditions.

Lets illustrate this to the point of absurdity. We'll compare HIV/AIDS and severe combined immunodeficiency (SCID).^[3] When comparing the immune systems of healthy and HIV positive individuals, the variation has a clear causal relationship with environmental variation; when comparing the immune systems of healthy andSCID individuals, the causal relationship is with a genetic variation. So is immunity genetically determined, or environmentally determined?

But SCID has an environmental component! It is only in the context of pathogens that people die from SCID. And HIV has a clear genetic component! HIV can wreak havoc only in the context of human biochemistry and cell biology. But stop the presses! We already know of some people who are naturally more resistant to HIV. In areas with little medical intervention, genetic variants conferring resistance to HIV are almost certainly at a selective advantage and will increase their frequency in such populations. Suppose that one day 999 in 1,000 people have inherent resistance to HIV — carrying and transmitting the virus, but living perfectly healthy lives with no need for medical intervention. How do we then categorise HIV/AIDS on the nature-nurture dichotomy?

These diseases are, of course, extreme examples which are far removed from normal developmental processes, but they illustrate how a great many variables affect each phenotype — and that's just when things go wrong. Unfortunately, so long as people continue to believe that this argument has consequences, they will continue arguing vociferously. From "gay genes" to "god genes", too many people are convinced that nature versus nurture is an important debate.

In summary: if I were Oliver James, I wouldn't be advertising the debate at all. Leaving aside the general pointlessness of it, he comes over as an even bigger arse than he did on The Late Edition. The fact that he confuses The Selfish Gene with evolutionary psychology sums up the value of his argument.

Footnotes

1. ^  Yes. Yes, I did start writing this post in early March. Yes, it has taken me nearly six months to get around to writing the second half and publishing it. Whatever.
2. ^  I know, what was I expecting from a programme featuring Hilary Rose?
3. ^  I know, I know, these do not reflect normal development, and are only superficially comparable diseases. It's just that normal development is so much more subtle: when I needed a crass example that spelled things out, this was the first that came to mind.

Discussions about Open Access publishing are constantly flaring up in the blogosphere. There is a lot of re-treading old ground as some struggle to catch up. This is particularly the case with criticisms of the author-pays or "article processing charge" (APC) publishing model. Under this model, rather than a library paying £30,000 for a year's subscription to a journal, academics pay around £1,000 upon acceptance of their paper for publication.

Members of the blogosphere tend to be quite young, many think that "open access" is a synonym for PLoS, and most are in real science, rather than publishing. What I am trying to say is that not all that many of them have actually followed the history of open access very closely — myself included, until around a year ago. So it was with great enjoyment that I read the summaries of this discussion from 2001, when this publishing model was first proposed:

Free access - who pays?

Seven years ago, even open-access evangelists were sceptical that it could be done. Now, even at three times the rather optimistic estimates (who said $50 would be enough to break even?), it's very firmly established. The pioneer in the field is running at a profit ("BMC hasn't yet reached the stature to impose fees."), the biggest funding agencies in the world have made it mandatory, and, in the meantime, the PLoS journals have come from nowhere to become one of the biggest brands in the industry.

Now, blogosphere, would you like to take a step back and reconsider some of those statements you've been making?

A few thoughts on Peer Review In The Dock (this evening, Radio 4) [Note: posted late due to ongoing database issues -- will move to a new host when I get the time.]

1. Nobody has ever questioned whether peer review is really needed: wrong. A lot of people have questioned this, and many experiments have been tried. The most prominent recent example is probably PLoS ONE (no reference to this in the programme). They very rapidly discovered that, yes, a minimum standard is peer review is required when running a journal. Perhaps moving to a non-review model is like communism: you need to have world revolution for it to have any chance of working; going it alone will just lead to your own collapse.
2. Peer-reviewers aren't trained: somewhat misleading. Reviewers, at least in the publishing model that I am familiar with, are actively publishing research scientists of at least medium seniority. Most will, while pursuing their doctorates, have participated in "journal clubs" (where the grad students get together to shred a published paper), and many will also have co-reviewed manuscripts alongside their supervisors (not strictly allowed, but very widespread). What all students certainly are trained to do, even at undergraduate level, is not to take the truth of published work for granted, and to watch for potential flaws. To teach science is to teach scepticism. Which brings me on to the next point...
3. Reviewers aren't all that great at spotting errors: so what? Academics and publishers know this. The system is designed this way. Review is supposed to be a basic filter for sanity and competence; it is only journalists who hear "peer-reviewed" and think it is the definitive stamp of authenticity. Like democracy and trial-by-jury, it is not used because it works, but because it fails less disastrously than the alternatives. (Incidentally, their example of introducing deliberate errors to a paper and seeing who notices them is not entirely fair: most papers are not only reviewed by the journals reviewers, but by the authors' colleagues before they submit the manuscript, and by editors before review.)
4. The last part of the programme was devoted to publication bias. Publication bias is a big problem. But it has little, if anything, to do with peer-review, and everything to do with publisher policies and author dishonesty. The only conceivable connection it has with peer-review is that some people still mistakenly believe that negative results aren't worth publishing at all -- something that journals like BMC Research Notes and PLoS ONE, and initiatives like trial registration are explicitly tackling.

The programme explored what is an interesting issue in academic publishing at the moment (there are more interesting issues, of course), but, I think, from the wrong perspective. While it discussed many very real problems with the system, these problems are all well known and acknowledged; for decades people have explored solutions, and there are many interesting current developments. The makers of the programme seemed mostly unaware of these.

This is, of course, the limitation of having a half-hour national radio programme about a topic like academic publishing.

Weston-super-Mare Grand Pier was destroyed by fire this morning.

BBC News

So, the following video was brought to my attention, and I was so impressed that I had to share. Admittedly, it took me some time to getting around to the sharing bit: it's difficult to find the motivation for an argument as patently absurd as that over gun ownership.

This is truly the most marvelous case study in rhetoric that I've seen all year. For those Americans who are unfamiliar with contemporary (and recent historical) British politics and society, allow me to dissect for you some of the more remarkable examples.

The video starts with Britain's "largest peacetime protest" (the untruth in this statement is only trivial). Primed with a title containing the word "guns", American viewers could be forgiven for assuming this protest had something to do with guns. It did not. The law was about hunting with dogs.

"Many are asking: where were these voices six years ago, when there was an outright ban on handguns?" Indeed. The fox hunters were largely apathetic towards a ban on handguns because you don't hunt foxes with handguns; but they got upset about the ban on hunting with dogs because they like hunting with dogs. Hence the protest regarding hunting with dogs, and the absence of the protest about owning handguns. Do you see?

But why was there so little opposition to the tightening of laws on handgun ownership? Because they came in the wake of the mass-murder of children with legally owned handguns. You can argue that this was an irrational reason to ban handguns, but it's the answer you're looking for.

"There has been a forty percent increase in gun crime since the law was introduced..." Wow. Crime statistics rise when something goes from being legal to illegal. I guess the ban on smoking in pubs and restaurants has similarly failed, since we've seen an increase in illegal smoking. This factoid is mediocre and meaningless: what do the real outcomes look like?

"The use of weapons in crime has risen dramatically," says Frank Cook MP. Actually, lets listen to that that again: "The use of weapons in crime has risen dramatically" (his emphasis, not mine). That presumably includes knife crime, the big one as far as popular discourse in the UK is concerned (though that too is largely a media fabrication, and the data demonstrate a falling rate of violent crime). I've no idea what Frank Cook's views on handgun ownership are, so I quickly searchedTheyWorkForYou .com for Frank+Cook+gun and, so far as I can tell, he has mentioned guns once in parliament during the timeTheyWorkForYou.com has been tracking debates. In a November 2005 session, Cook mentioned, as an aside, that the post-Dunblaine restrictions on gun ownership were knee-jerk. And he's right. But it doesn't paint a picture of a man tirelessly crusading for a fundamental right on which our safety and liberty depends.

More soundbites: police morale is "at an all time low." Wow. I didn't even know there was an objective rolling record of police "morale"! Police morale has been a little low lately: they have a pay dispute. Not a gun dispute, you understand. A pay dispute. Police safety^[1] is an empirical question which is not measured in "morale".

Next it's over to Tony Martin -- the poor defenceless old farmer who shot violent intruders in self-defence. Er... yeah. Not the Tony Martin with paranoid personality disorder who shot a fleeing teenager dead, hid the weapon, and went to the pub, then? Tony Martin is not a good poster boy for the right to bear arms.

--

I don't think we saw a single datum in the video. There were a lot of anecdotes and soundbites, a lot of selective footage and an absurdly crude misrepresentation of the situation in the UK. But the issue surely just rests on empirical questions? Where are the data on this issue? Well, so far as I have been able to ascertain -- and it's difficult to be sure of anything on the topic when there are two polarised dogmas desperate to make the loudest and most preposterous noise -- neither side have much going for them. Being armed does nothing to make you measurably safer; but then, neither does a gun ban or amnesty. Arguments on this issue tend to be about simple solutions to complex social problems, and each side seem quite content to defend their positions with arguments as flawed as those above. They're the best arguments they've got.

Continue reading under the fold...

Hah! Made you look! No, but seriously...

The schizophrenic argument of the creationists goes something like this (my paraphrasing):

• How can we believe anything these scientists say when they keep changing what they say to accommodate the new things that they discover?
• How can we believe anything these scientists say when they just worship Darwin and talk about Victorian ideas. Haven't we discovered anything new since then?

Well, it's true that many of Darwin's ideas are still relevant to science today. Many people still use the modifier "Darwinian" when talking about "selection": Darwin's description of natural selection has stood the test of time with only modest new discoveries. And it's also true that biology has grown to incorporate new facts -- remember that Darwin was never acquainted with the field of genetics, a 20th century development. Indeed, genetics -- the mechanisms of inheritance -- was where Darwin got it all horribly wrong.

Darwin was sympathetic to the idea of the inheritance of acquired characteristics -- that the skills we work hard for and the afflictions we curse ourselves with, the blacksmith's biceps and the scholar's spectacles, are routinely inherited. The popular hypothesis at the time was that "hereditary particles" flow through the body from every limb and organ and into the sperm and egg (mostly the sperm, remember that this was the 19th century, when women's role in forming children was seen as something equivalent to a flowerpot's role in germination). The hereditary particles flowing from bulging biceps or myopic maculae would surely reflect their sources? Only after Darwin had departed did we discover that the hereditary particles spend all of their days closely guarded in the ovaries and testes, having only a passing acquaintance with the activities of the biceps.

Darwin got something wrong, and that's OK. Darwin did not set himself up as infallible, issue decrees, or talk of absolute certainty. He is rightly remembered for the important discovery that he made, and for those ideas of his which have stood the test of time, but he is not the messiah. Sometimes I think creationists have a hard time comprehending these things. Stuck in a world where there is nothing new to learn and everything is revealed by authority, they assume that their opposition are in the same situation, only with a different holy book. In a world where divine revelation is the purest source of knowledge, they are bewildered by a system in which knowledge grows and blurry pictures slowly sharpen. In a world where everything they know flows through pope or pastor, they assume that Darwin must be our leader, and we must be his flock. Knowing that their belief system depends upon defending the infallibility of their book, they seem to think that demonstrating Darwin's fallibility is sufficient to undermine evolution.

Welcome to the second Carnival of Molecular and Cell Biology!

Medical research

The existence of a dedicated molecular and cell biology carnival reflects the pace at which this field is discovering exciting and useful knowledge. Molecular genetics and gene expression, for example, is crucial to our understanding of a collection of what are essentially genetic diseases -- cancers. Alex Palazzo at The Daily Transcript discusses this in the context of recent findings on the role of miRNAs in cancers in "Let7 miRNAs, Lin-28, Cancer and Stem Cells."

Meanwhile, over at one of my favourite new blogroll additions, Blogging for Bacteriophages, Tim Sampson reviews recent research on the workings of tuberculosis in "A Fatty Acid Synthetase is Necessary for Active TB Infection". With implications for drug development, we see again how reliant modern medicine is on the field.

While drug resistant TB is beginning to make this disease an issue in developed countries again, it mostly remains one of those neglected diseases of the developing world. Another disease that has been somewhat neglected, though for different reasons, but which is benefiting from research in cell biology, is depression. BrainbloggerShaheen Lakhan presents "Inflammatory Markers Altered in Depression and Suicide."

Emphasising the role of genetic damage in cancers again, iayork, author of the wonderful Mystery Rays from Outer Space, points to endogenous retrovirus as a target for immunotherapy , in "HERVs: zombie target practice for immunity."

There's more on cancer immunotherapy in "Immune cells unexpectedly fight cancer." This one wasn't submitted by the author, but I wanted to include it as it comes from the marvelous new blog of Cancer Research UK, which you should all be reading!

Basic research

While molecular and cell biology is crucial to medical research, I very much doubt that's what keeps you reading. You're here because, like all good science, it's exciting. One can never fail to be entertained, for example, by research looking at the origin and evolution of life. In "What's a cell-adhesion protein like you doing in a unicellular organism like me?", Bruce Olsen reviews the origin of multicellularity, and the communication and cooperation of our single-celled ancestors.

Indeed, my own offering goes back to the origins of the eukaryotic cells, and reviews a recent publication looking at horizontal gene transfer in the ancestors of chloroplasts: "Light years upstream, dipping in the River out of Eden."

News and views

sparc presents Ancient DNA, at molecular B(io)LOG(y).

Short reports

96well, on the source of luminescence in fireflies, tells us that "In the beginning was the fat."

---

Thus concludes the Molecular and Cell Biology Carnival. We've explored just a tiny fraction of the complexity of life and disease, but demonstrated the importance of the molecular and cell approaches to these topics. With almost all of our items discussing recently published research, I hope we have also demonstrated the ability -- value, even -- of blogs for digesting and communicating complicated new ideas.

Keep an eye on the MCB Carnival website for the schedule, or sign up as a host by emailing our founder, The Skeptical Chemist.

It would appear that I'm hosting the Molecular and Cell Biology Carnival on Sunday. This, I suppose, involves me finding some last minute creativity to put the thing together.

Anyway, due to the unreliability of the BlogCarnival.com system, you can submit items by leaving a comment here, or emailing me. I will be accepting the usual mix of reviews and commentary on research, but I'll also find room for short posts and "classics" -- items you're especially proud of, but which were written long before the carnival was created.

Update: my apologies -- due to the problems with BlogCarnival.com I do not yet have the items that have been submitted. 12/5/08

I've talked about Horizontal Gene Transfer (HGT) on the blog a few times before, particularly in the context of bacteria acquiring genes for things like antibiotic resistance, and in the context of operons (more of which in a week or two). Jeferson Gross, Jörg Meurer, and Debashish Bhattacharya have an interesting story to tell about HGT in last week's BMC Evolutionary Biology.

Firstly, the brief introduction to HGT for those unfamiliar. Genes like to make copies of themselves -- or rather, natural selection tends to favour those genes which are good at making copies of themselves. There are two principal categories of methods by which genes ensure their presence in increasing numbers of individuals. The obvious one is vertical transfer: when cells divide, the daughter cells each contain the same compliment of genes; and offspring inherit their genes "vertically" from their parents. The other category, horizontal transfer, makes things so much more complicated and fun. In horizontal transfer, a few genes (usually a fraction of the total possessed by the individual) are copied and given to another individual. That individual does not have to be closely related -- indeed, in extreme examples they can be as distantly related as a bacterium and an animal. HGT is common between bacteria, but rare in eukaryotes (animals, plants, etc).

HGT has some very interesting consequences for the process of evolution, and for the way we see the history of life on earth. The image of the "tree of life" begins to break down, especially in bacteria -- there is no longer a branching lineage which can be traced back to the universal common ancestor. Rather, there is a network of crisscrossing lineages, diverging and merging. Pairs of genes depart, while other pairs meet. The genomes of modern bacteria are chimeras made from bits and pieces of very different ancestors. This makes things difficult for those researchers trying to describe what life was like a few thousand million years ago, when the earth was young.

It is generally believed that ancient life experienced a great deal of HGT, and genes were flowing all over the place. This view may to some extent have arisen as a result of the common image of ancient life as being just-like modern bacteria -- simple, unsophisticated and dull. Trouble is, modern bacteria are not simple or dull, and they have particularly sophisticated devices to enable HGT. The process of "bacterial conjugation" involves the construction of molecular needles, the transmission and recognition of "mating signals", and the activity of a specialised enzyme complex. This is a complicated system which must have arisen at some point through evolution. There is therefore no reason to automatically believe that HGT has been rampant forever, and whether HGT was common in ancient organisms is an empirical question.

How do you go about answering a question like this? It can not be answered by any fossil, and the nature of HGT makes it very difficult to get an answer of any use by sequencing genomes and drawing trees. Fortunately, there is a window -- or rather, several windows -- on ancient life. There is a group of microorganisms which have become totally isolated such that they have been unable to participate in HGT. Though they have still been subject to other evolutionary process, these organisms provide a good estimate of their free-living ancestors of 1,500 million years ago (mya) -- they are living fossils, if you like. The organisms -- if they can still be called that -- are plastids. The plastid that you're most likely to be familiar with is the chloroplast -- responsible for photosynthesis in plants. Chloroplasts are the descendants of once free-living cyanobacteria. Around 1,500mya a cyanobacterium found itself stuck inside another, larger cell. The cyanobacterium found its new shelter comfortable, while the host cell found the cyanobacterium's photosynthetic nutrients useful; the rest is history.

So things are as simple as looking at the genes in the chloroplast genome and determining where they came from? Well, actually, evolution never makes things that simple. Over the millions of years that the chloroplast has been sponging off plants, bits of the chloroplast genome have migrated into the plants' nuclear genomes. Chance events got those fragments from the chloroplast to nucleus, I imagine. Selection perhaps favoured their new home -- for safety from mutagens, access to more sophisticated control of gene expression, or more advanced DNA repair mechanisms, perhaps. Whatever the reason, we now find bits of the plant genome that look uncannily like bits of the cyanobacterial genome.

So, now we get to Gross et al's contribution to this story. In their paper they look at the men family of genes. This family contains eight individual genes (A-H), the products of which are enzymes involved in a photosynthetic pathway. These genes are very similar to other metabolic genes found in bacteria, where they are clustered in operons. Gross et al found that in plants, seven of these genes are found in the nuclear genome, but we can be reasonably sure that they originate from bacteria (via chloroplasts) because they are also arranged in an operon-like structure in the plant genome (plants do not usually have operons). Additionally, a relic of the operon containing these seven genes can still be found in the chloroplast genome, albeit mutated and unused. Now, if you believe John Maynard Smith, the fact that these genes are arranged as an operon is itself evidence for HGT, as JMS' hypothesis is that operons evolved to aid HGT.

Of course, not everybody does believe JMS, and alternative hypotheses about the selective advantage of operons have been proposed -- for example, that operons are the simplest way to control and coordinate the expression of a team of genes. But Gross et al have additional pieces of evidence. Firstly, one of the eight genes, menA is not found in the cluster of genes, suggesting that in the ancient ancestor of plastids this gene had a separate origin to the seven genes in the operon. And secondly, having created phylogenetic trees of the men genes from plants, algae, and a variety of bacterial species, they find that several (but not all) of the nuclear encoded men genes from plants look uncannily like those from green sulphur bacteria -- even though they almost certainly found their way into the nuclear genome via the chloroplast.

There are lots more details and suggestions for the histories of these genes, but I needn't bore you with them. The important point is that the simplest explanation for this fossilised mosaic genome is that HGT was well established 1,500 mya, and we are therefore justified in making the assumption that HGT has been around for a significant fraction of life's history. Perhaps, even, early life really was just one big gene pool -- a river out of Eden, with genes mixing in the eddies and rapids.

Gross, J., Meurer, J., Bhattacharya, D. (2008). Evidence of a chimeric genome in the cyanobacterial ancestor of plastids. BMC Evolutionary Biology, 8, 118. DOI: doi:10.1186/1471-2148-8-117

With apologies to Mitchell and Webb, and further apologies if I invoke Godwin's Law along the way.

Pope: Very well. [puts phone down] They're coming. Now we'll see how these atheists deal with a crack vanity-published hack writer division.*

Cardinal: uh... papa?

Pope: Have courage my friend.

Cardinal: Yeah, ah... Papa, I've just noticed something.

Pope: These atheists are all amoral sinners.

Cardinal: Have you looked at our miters lately?

Pope: Our miters?

Cardinal: [nods] The badges on our miters. H.. have you looked at them?

Pope: What? No? A bit?

Cardinal: They've got Roman torture devices on them.

Pope: huh?

Cardinal: Have you noticed that our miters have actually got little pictures of devices that the Romans used for horrible painful murder on them?

Pope: I er.. I don't ...

Cardinal: Papa... are we the baddies?

* Yes, yes I did just make fun of vanity published writers on a blog. And?

Humphrey Lyttelton, 1921 - 2008

Humph tells me he has to leave us now as he's been invited to a club night by St Peter, and this is something of a climax for him. He'll drop everything to be taken to heaven by St Michael. He says he can't wait to see the kindly old keeper-of-the-keys' famous entrance and part his Pearly Gates, and I can just imagine St Peter's joy as Humph gets red in the face blowing on his trumpet all evening. There are rumours that God might come and play with his instrument too -- he has needed cheering up lately as the Archangel Gabriel keeps rubbing him up the wrong way, and he was last seen giving Gabriel a good mouthful.

St Michael won't be joining them as he's off to the pub with Mary. He likes nothing more after a long hard day than to rest his staff in the Queen's Head, and once Mary gets the pints out he'll be up all night, and finish off with a stiff one in the early hours. Mary, bless her, never learns to drink in moderation, and I know she'll be feeling a little dicky in the morning.

Samantha will be there, and she tells me she has been baking some of Humph's favourites, and bought the whiskey that he loves. I know that she's very much looking forward to having him try her muffins and liquor out in the Garden of Eden.

Humph, you touched us all, blew us away, and leave us all gushing this weekend. We raise a glass to the legendary Humphrey Lyttelton, and can only play another round of Mornington Crescent.

I'll open with Great Portland Street.

. . . imagine a puddle waking up one morning and thinking, "This is an interesting world I find myself in, an interesting hole I find myself in, fits me rather neatly, doesn't it? In fact, it fits me staggeringly well! Must have been made to have me in it!"

Douglas Adams

It took me a while to work out what was bugging me, but I think I've got there. We were at Skeptics in the Pub rambling about epistemology and other such nonsense, when for whatever reason, somebody felt the need to bring up the example of "chemical" versus "natural" -- something that I discussed here a few weeks ago. I did my quick piece on "flipping the Necker cube" and looking at the nasties in our environment in terms of our evolution: nothing is intrinsically healthy or harmful, it is only in the context of our evolved anatomy, physiology and biochemistry that it becomes so.

I was up against quicker witted and more articulate fellows than myself, and after a long day, a couple of hours of Bad Astronomy, and more than a couple of pints, I was not able to adequately put into words just why the response to this point was wrong. Since the point about flipping theNecker cube is one that I have also made on the blog, I thought I would discuss it again here, in-case anybody else has misunderstood the point that was being made.

First, a rough characature of that response: by talking about evolution and nasties I was elevating humankind to a position that we don't deserve. Man is a tiny part of life on earth, and we shouldn't flatter ourselves to believe that the universe is deliberately out to get us, any more than we should flatter ourselves by believing that the world was made to have us in it. God is famously fond of beetles and bacteria, after all.

Of course, the problem, so obvious now, is that the Necker cube has not been flipped at all. We're still trying to answer the question of why the nasties are nasties by looking at how they got to become nasties. The other side of the cube is to try to answer the question of why nasties are nasties by looking at how we evolved. This means recognising that we have been built, bit by bit, from scratch. Every system, organ, tissue, cell type, metabolic network and enzyme has a birthday, somewhere in the depths of time. They have been shaped by selection to perform a function with some minimum of efficiency, and to have a minimum of robustness in the face of countless environmental variables.

And it is only by having encountered particular values for those variables that evolution can have prepared us for them. Evolution has no foresight and goes no further than those minimum values. It picks the first successful candidate solution that it finds, and it's just luck if it solves more problems than were asked of it. If a population encounters a novel chemical, sourced from a plant for example, evolution will not have prepared the population for that chemical. That does not mean that we are elevating humankind by suggesting that the plant is producing the chemical with that specific population in mind.

Not convinced? It helps if only one of the parties is evolving, so we'll ignore plants, bacteria, and xeno-biochemicals altogether, and just watch how man performs against the elements. An enzyme that has never encountered a particular pH or temperature, for example, can reasonably be expected to perform poorly under such conditions. Break, even. We are not witnessing a conscious decision on the part of God or Mother Nature or the Universe to challenge us with extremes of pH; it is merely the outcome of an unconscious "decision" not to prepare for such events. Acidophilic archaea, organisms that have evolved in the context of extremes of pH, have enzymes that are similarly unprepared for the conditions in which we live.

When you look at it from this angle, it doesn't just seem obvious that species are adapted to that which they have experience of, and vulnerable to many things that are unfamiliar to them. It seems absurd to even bring up the issue of whether nature gives a damn about us. It is we who are giving the damn. And that is the point of Douglas Adams' puddle.

I intended to post this a couple of weeks ago, before Ham did his London lecture. Since nobody bothered going anyway, I ended up procrastinating instead.

I listened to a sermon^[1] by Ken Ham, creationist head of Answers in Genesis, the other day. I was erm ... researching a role? Anyway, it was great fun. My knowledge of church services is limited to the Anglican tradition, and it was very educational to hear how things are done evangelical style. I won't bother dissecting Ham's argument bit by bit -- though it's worth mentioning the occasional bursts of outright Lying For Jesus, such as the claim that textbooks state that there are higher and lower races of man, or the conflation of species (of cats) with breeds (of dogs). You know, things so absurdly wrong and depressingly easy to fact-check. Rather, what really interested me was the way he wove two very different classes of (equally fallacious) arguments together. On the one had were his creative truth-claims in favour of biblical literacy and against the findings of science. On the other were arguments about perceived consequences that acceptance of evolution has for morality. Ham flickered back and forth between the two, ignoring the distinction. It's an acceptable rhetorical technique, I suppose: mix claims about what is true with scare stories about what happens if you don't believe it. I'm sure many of the arguments for atheism could even be charged with using this technique at times, and it's a staple of politics and tabloid news. But I think that it says something very interesting about the motivation of creationists.

Ham's argument from consequences comes down to this: if the bible is literally true, God determines morality. If evolution is true, morality is based on man's fallible word. And you know what? He's right. The bible is wrong about an awful lot of things (sometimes it's just asking too much to believe that it was intended as allegory), and God does not determine morality. To paraphrase HectorAvalos : it is not sufficient to demonstrate that the bible gets one fact right in order to demonstrate that it is is useful, relevant, ethical, or the revealed word of God. But one inaccuracy is all that it takes to prove that it isfallible and questionable.^[2] Ham therefore believes that it is his duty to defend every word of the bible as the truth. Only that with "save their souls." The end goal of promoting creationism is not to have everybody believe in creation, but to fight the rise of the "pagans." (Lol.) Ham believes that if people are taught that it doesn't really matter how God made the world, they will question whether he made it at all. If people are taught that it doesn't really matter whether everything in the first book of the bible happened, they will question whether the events of the Gospels really happened. And you know what? I can't argue against that. Our only difference is that Ham believes that this is a bad thing.

The tactic of mixing truth with consequences is something that has been inherited by the intelligent design movement. Take the Wedge document, the DiscoveryInstitute's 1998 manifesto (leaked, and now subject to desperate attempts at distancing and damage control from the Disco Inst.). The document makes vague appeals to science here and promises research programmes there, but it is primarily concerned with the perceived effects of "scientific materialism". Socialism is the preferred bogeyman of the Disco Institute, though the link between evolution and socialism never seems far from confused. Or, of course, we have Ben Stein in theater(s) (for one week only) rather offensively lying for Jesus about racism and playing games with the holocaust.^[3] School shootings, abortion, homosexuality, and all the other traditional demons are these days the responsibility of "evolutionization".^[4]

Claims about the truth and claims about consequences are not the same thing, and I'd be rather offended if somebody gave a lecture or made a film mixing the two so thoroughly and expected me not to notice.

References

1. ^  Available here.
2. ^  From his Minnesota atheists lecture, if I recall correctly.
3. ^  In Expelled.
4. ^  Attributed to Tom DeLay, 1999. "U.S. Republican politician blames the Columbine shootings on "evolutionization".

One last thing about hybrid embryos. Yeah, yeah, I know. Old news and all that. It takes me a while to get from shouting at the radio to writing up a post, OK? Anyway, it's about something that struck me while listening to Radio 4's Leading Edge on theiPlayer while half awake the other day. Leading edge is a pop-science programme: it's aimed at the masses, but it's supposed to have higher standards than news bulletins when it comes to explaining reality in detail. This particular gem of absurdity hadn't occurred to me before; perhaps I've become somewhat immune to the crazy misunderstanding of science in the news, but I really notice it when it comes to science programmes.

The crime in question? Being so obsessed about DNA. The problem with hybrid embryos, apparently, is that you'll be mixing human nuclear DNA with a tiny (really tiny) amount of mitochondrial DNA (mtDNA) from other mammal species. On Leading Edge, the correspondent went on to allay our fears of such an unholy chemical congress by explaining that this has been done many times before with pairs of mammal species with a conspicuous lack of devastating explosions, zombie epidemics or eightlimbed monster mice. He went on to describe the mitochondrion for us (the "power pack", of course), the percentage of our DNA which it actually contains (point-twelvety), and the number of copies in which it found in the cell (17 1/2 billion, except on sundays or if you earn over 20% of your annual income from savings and investments).

What do you mean, I'm not taking this seriously? Oh, well, maybe I do think that perhaps the whole hybrid-embryo-in-the-media thing is just verging a little bit on the totallybatshit insane. Does anybody actually think that the religiously motivated opponents of science are worried about mtDNA ? Will explaining mitochondrial copy number make them feel better? OK, no, but what about all the non-partisan chaps who have heard these militant bishops on the radio telling us that hybrid embryos will be the worse thing that humanity has ever done, you ask? They will surely have concluded that there must be some genuine controversy involved, you add? Well, maybe.

But if that is the case, how is a discussion of DNA going to help anyone understand that the "controversy" is not scientific. What, indeed, does DNA have to do with anything? I could give you a vague introduction to what DNA has to do with hybrid embryos, and indeed what DNA does not have to do with hybrid embryos. But can the journalists who are covering this story? No. It would appear that they have all be on How To Talk About DNA In The Media 101. DNA is, you'll be interested to learn, the blueprint for the body; and by the sounds of it, DNA is pretty much the only thing in the cell that does anything at all. Oh, except for the mitochondria, obviously. But then, they contain their own DNA,init?

Confused accounts of biology aside, you can not solve a religiously motivated controversy by talking about science -- not in a week, anyway. The barking bishops have made it quite clear that they couldn't give a damn about the science. Facts mean nothing when the truth is divinely revealed. So you can discuss the hybrid embryo controversy or you can discuss the hybrid embryo science. Combining the two convinces nobody, but gives the impression that the controversy has some sort of scientific legitimacy. It doesn't.

Somebody in the Nature Podcast editorial team is clearly not a fan of "new atheists". The "guest rant" spot, or whatever it is they call it -- podium, I think -- has been given to a succession of lectures on the "new atheists" and the compatibility of science and religion. Take John Durant, director of the MIT museum and self-contained pun, who took the spot on February 21 (yes, I know, I've been a little slow in getting 'round to publishing this one). Durant tells the story of atheist Darwin and Asa Gray, American Christian botanist^[1] and populariser of evolution. Darwin and Gray were, shockingly, good friends and correspondents, despite their overwhelming incompatibilities. Not like these days, when we "Darwinists parade [our] science under the banner of militant atheism." Oh yes. He played that "militant atheism" card with style.

Indeed, can you imagine screechy Richard Dawkins being friends with, say, his local Anglican bishop? And what on earth could drive Dawkins to such shrillness anyway? Why can't he be more like those polite politicians in the Commons, who never raise their voices and argue? I mean, just look through any newspaper. All of those columnists being calm and keeping their opinions to themselves. Why do these atheists think that they alone have the right to start a public discussion?

Whatever. You get the point. It has been argued to death already, and if Durant is too unimaginative to spot the absurdity of his argument, and too lazy to actually look at the responses that the "militant atheists" have already made to the argument, there's not really much point in me wasting your time going over old ground. But the real reason that I couldn't let his rant pass is his conclusion:

If there were more Darwins and Grays in the world of science today, discussions about evolution and creation could continue within science, instead of being relegated to the lunatic fringes of the so-called culture wars.

WHOA! Hang on a moment! Discussions of creation have a place within science? Now you've really lost me, and I think you may perhaps have lost some of your fellows in the "militant atheists are too screechy" camp, too. And it's not like I can be accused of misinterpreting "creation" in this instance. Durant is not talking about discussions of abiogenesis or the anthropic principle. He is talking about the sort of "creation" that is currently on the "lunatic fringes". Like seeing the signature of the Almighty creator in mitochondrial proteins, or asserting that the universe was created on a pleasant September afternoon in 4004 BC?

We do have modern Darwins and Grays. None of them think that polite discussions of creationism belong in science.

Footnotes

1. ^  A botanist who happened to be Christian, that is. I don't mean "Christian Botany" like "Creation Science".