While we're on the subject. Any Questions is typically about politicians from each of the main parties trying to win cheap points while making the public aware of their party's policies on the events of the day. It ends with the "and finally" question -- the silly question, where everyone calms down and shows us that they're human, and they can share a laugh with their colleagues on the opposite benches. Which is the main reason why I object to the "and finally" question this week being "should we return to the moon?"

Historian Andrew Roberts isn't sure we should have gone there at all. "We got teflon for cooking bacon and eggs, but not much else."

"Velcro!", exclaimed Will Self. Following a question about the uses of velcro, we have some banter about Vauxhall clubs.

"Think of the rainforests," I paraphrase Linda Colley. "Won't somebody please think of the rainforests?"

Finally, Rod Liddle says, "well I think it was exciting."

Yes! Leaving aside the fact that the technology that has come out of space exploration is infinitely more varied and useful than Andrew Roberts' imagination can cope with; leaving aside the wonderful and beautiful scientific discoveries that have been made; space exploration is just damned exciting. The astronauts of the Apollo missions travelled further from home than any man has ever been, and returning to our neighbour, barren and grey though it might be, would symbolise the fact that mankind has not stopped dreaming of taking that next step, to more wonderful places, and discovering our universe. To satisfy our innate yearning for adventure, discovery, and understanding of the world.

The answer to this question would say far more to me about a politician than their ability to repeat the party line on this week's scandal, or praise a recently deceased entertainer that they had barely heard of.

Any Questions, one half of BBC Radio 4's weekly foray into the realm of mindless US-style talk radio bigotry, this week invited a panel of historians, novelists, and journalists to share their poorly considered thoughts on current affairs with the nation. A question regarding the situation in Iran was asked, and after ten minutes of the panelists tediously repeating what they had read that week from real foreign affairs experts, somebody mentioned twitter. I'll pass on wordsmith Will Self's clumsy attempt at a joke ("the only circumstances in which I would twitter is if a songbird flew into my mouth"), which somehow prompted screeches of delight from the audience of children and mental subnormals, and go straight to the comments of Rod Liddle.

Rod Liddle, left-of-centre columnist for right-of-centre newsmagazine Spectator and former editor of Radio 4's flagship Today Programme, joked about the use of twitter by celebrities and politicians being all about what they ate in the restaurant last night (oh, by the way, Rod, I've got 2008 on the phone -- they said something about wanting their joke back?). Even if that were true, so what? I've never read the Spectator, but I learn from their website that if it were my wish to do so, I could enjoy such features and columns as boring woman has lunch -- sorry, splendid lunch; some guy gets his hair cut; and painfully arsenumbingly pointless woman pours her heart out over the uniquely middle class problem of "how to start a letter to your sponsored child". My God, Spectator, don't you realise? I don't care. I don't care about these irksome morons, I don't care about their lunch, their haircut, or their sponsored child, and I don't know why you're telling us about them. You have taken three retards, stapled them together, and are asking people to pay �3 to read this crap.

For God's sake, traditional media, take a step back and look at what you're doing. You look ridiculous. Radio 4 is broadcasting Anne Widdecombe's considered views on designer shoes, and you wonder why we're all off reading the science minister's twitter feed? You don't see the connection between the Spectator's bizarre dogmatic belief that the raving troll Melanie Philips somehow has something worth printing, and our mass defection to the blogs of professors? Channel 4 broadcasts Rod Liddle's spectacularly moronic comments on atheism and eugenics, and you still don't get why we've all gone to watch YouTube and TED talks?

Of course there are some tedious twitterers. Of course there are plenty of people who couldn't give a crap about my thoughts, or the thoughts of those bloggers and twitterers that I follow religiously. And of course there are plenty of people who, like me, could not care less what Rod Liddle thinks about anything, let alone the catalogue of topics that he mistakenly thinks he is qualified to comment on. This is the nature of broadcast media, and it always has been. And that is not a problem. It doesn't matter if I am not interested in somebody's restaurant-related tweets, because I can ignore them. It doesn't matter if somebody blogs on a topic that I do not care for, because I can scroll on past. It doesn't matter if Channel 4 makes poorly-researched documentaries , because I can switch channel. It doesn't matter if my newspaper prints columns on haircuts and sponsored children, because I don't have to read those if I don't want to. Just because something is published in a broadcast medium, does not mean that you are the target audience, and the author is seeking your approval. The difference, as I'm sure you will have noticed, is that if nobody wants to read my tweet or blog post, I will have wasted the few seconds or minutes I put into crafting it. If nobody reads your column or listens to radio programme, your publisher goes bankrupt and loose your house.

One comment made on twitter is not going to change the situation in Iran. Nor is a comment made by a novelist on Any Questions. The difference is that the twitterers are aware of these facts.

In February I announced the Cancer Evolution series. Finally, here is part one of the two part introduction!

"Evolution", as applied to cancer, is not just a metaphor standing for "change" or "development". Cancers really do evolve: tumours are populations of individuals which reproduce and show variation, leading to evolution by natural selection. In our picture of evolution, cells -- specifically somatic cells, the dead-end cells of the body (as supposed to sperm and eggs) -- play the role of individuals within populations. To understand how and why they evolve, we must therefore look inside the cells, and find out how they work. This post serves as an introduction to cell and molecular biology, which I hope, together with the forthcoming introduction to evolutionary biology, will be enough to allow non-biologists to follow the details in the rest of the series.

Cancers are diseases of genes and genomes

Our cells are capable of performing thousands of different process. They must, for example, grow and divide; respond to external stimuli, like hormones or environmental change; store and retrieve nutrients; make products to release from the cell; and eventually die gracefully. These processes, and many more besides, take the form of chemical reactions -- lots of very complicated interacting chemical reactions that add up to the events listed. Cells are full of molecular tools which encourage these chemical reactions to occur, and which make sure that they are finely controlled. These tools are typically enzymes, a class of protein. They are chains of different building blocks: several types of "amino acid" arranged in a specific pattern -- a pattern which determines the protein's shape, and therefore its properties, such as function and efficiency.

The sequence of amino acids in a protein, and therefore the protein's properties, are represented in turn by genes. Genes are themselves sequences of a different building block -- nucleotides -- and their sequences correspond to the protein sequences. Indeed, one group of enzymes is dedicated to the task of translating those gene sequences into the sequences of new enzymes during gene expression. A small change in a gene sequence (an inherited or acquired mutation), though, can have a range of effects on the enzyme that it encodes, and some of those effects can be catastrophic. Many mutations will go entirely unnoticed, and others are negligible. But if a mutation hits the code for a crucial location in an important enzyme, that tiny change in sequence might knock out (or switch permanently on) a whole cellular system.

This is how cancers tend to get started: a mutation affects the function of an enzyme, changing that enzyme's ability to control chemical reactions, and thus a key system in the cell goes unregulated and that cell starts behaving badly. As cancers progress, they pick up further mutations, disrupting more and more cellular systems, including, as we will see in a future post, the (imperfect) systems that are in place for detecting and correcting mutations. Once those systems have been damaged, there follows major deterioration of the genome, and the ability of the cell to function. This progressive deterioration of the genome, and the variety of associated cellular systems, are what we will explore in this series of posts.

Cancers are diseases of cell growth, division, and death

Cancers can also be described as diseases of the cell cycle. Tumours are, after all, groups of cell clones proliferating beyond control. The life of a healthy cell is highly regulated: new cells are created by cell division ("mitosis"); cells differentiate into specialised occupations in the body; and when they grow old, they undergo a process of programmed cell death ("apoptosis"). These events, like any other in the cell, are regulated by enzymes, and it is disruption to these processes which causes cancers.

Cell division requires the activation of a number of cellular systems, to perform tasks such as the duplication of the cell's genome and the production of many cell components, such as its enzymes and membranes. It can be divided into a number of discrete stages. At rest, the cell is in the first "gap phase", G1. During G1, the cell is just waiting for the right moment to start division. It monitors the conditions of its external and internal environments, and awaits the "proceed" signal. The cell runs its "restriction checkpoint": a system for testing the integrity of its genome, to ensure that it is in good condition. If the cell passes the checkpoint, it is ready to divide; if it fails, it will refuse to divide (becoming "quiescent" in the "G0 phase") and may even activate a system of controlled self-destruction called "apoptosis".

The first sign of cell division activity is when the cell is prompted into the "synthesis phase", when the cell's complement of chromosomes -- its genome -- is duplicated. Synthesis is followed by another gap phase, G2, during which the "G2 checkpoint" must be passed. This "checkpoint", like the restriction checkpoint, is a system for testing genome integrity, and specifically whether genome duplication has been successful. Very small "typos" are to be expected during genome duplication, and the checkpoint activates DNA repair mechanisms to correct these. If the cell passes the checkpoint, it is ready for the big event, mitosis: the carefully choreographed series of processes by which the cell divides. If it fails, the cell will activate apoptosis.

The system of checkpoints and DNA repair are imperfect, and at every cell division, the genome inevitably picks up some (mostly harmless) mutations. As a precaution against cells picking up too many small mutations, which together might add up to produce harmful effects -- including cancers and the effects of aging -- cells have another control system: programmed replicative senescence. This system counts the number of divisions that a cell has been through, and when the number grows too high, the cell will fail the restriction checkpoint, growth and division will be halted, and the cell will become senescent or die.

Synthesis: social control genes

Cancers occur when mutations cause cells to grow and divide beyond their normal limits, and to outlive their programmed senescence. The common factor between cancer as a genetic disease and cancer as a cell lifecycle disease is the genes whose protein products are part of, or influence, the systems of cell growth, division, and death. These genes are oncogenes (or more properly, proto-oncogenes) and tumour suppressor genes. The products of oncogenes typically act, within strict limits, to cause the cell to proceed through the cell cycle and to divide. The products of tumour suppressor genes typically act as a check on cell division. When these genes are mutated such that they can not perform their function correctly, or when regulation of the expression of these genes is lost such that too much or too little of the enzyme is produced, the cell cycle becomes dysregulated, and a cancer can form. We will meet some specific oncogenes and tumour suppressor genes when we look at the cellular systems and events involved in cancer.

Oncogenes and tumour suppressor genes can be directly involved in the mechanisms of the cell cycle and the systems of checkpoints, repair, and programmed cell death. But just as often they are part of the complicated network of interacting signals that tell the cell what is happening in the body around it, and what its various systems should be doing. Cell division does not occur spontaneously, but when the cell detects that conditions are right for proliferation. Thousands of varieties of "receptors" sit on the surface of the cell. These proteins contain docking sites for specific molecules, known as the receptor's "ligand", found in the cell's environment -- nutrients in the blood, and hormones released by other cells, for example. When a receptor detects its ligand, it sends a message inside the cell, typically by activating a "cascade" of intracellular signalling molecules -- the receptor activates messenger i, which activates several of messenger ii, which together activate many of messenger iii. Messenger iii might then, for example, tell the cell to change its pattern of gene expression so as to push it into the synthesis phase of the cell cycle. There may also be cleanup-enzymes i-iii which go around switching the messengers off at a constant rate, such that the signal ceases when its activation by the receptor ceases.

Cell signalling networks are very complicated, with different systems interacting, and many messengers carrying subtly different messages depending on the context and concentration in which they are active. It does not require much to change in order for a messenger to go off message. Messengers i-iii are therefore potential oncogenes: if they were to be mutated so as to be always on, the cell would constantly think that it is receiving the command to divide. Cleanup-enzymes i-iii would be tumour suppressor genes, producing a similar state were they to be mutated to an always-off state. The quirks and complexities of cell signalling in cancer evolution will be explored in several of the forthcoming posts of the series.

Recapitulation

Cells grow and divide to build and maintain our bodies. Our bodies functions arise largely out of the events and complicated and carefully regulated systems within our cells, which are mostly carried out by molecular machines called enzymes. These enzymes are produced by the genome, a set of instructions which is inherited during cell division. Mistakes in genome duplication -- mutations -- can cause the production of malformed enzymes, or incorrect concentrations of enzymes, and thus cause the disruption of cellular systems. When this happens the cell behaves badly, and might become cancerous. These enzymes are known as "oncogenes" and "tumour suppressor genes" according to their activities, and they are typically involved in the systems of cell growth, division, and death, or genome auditing and repair, either directly or as part of cell signalling networks.

The next post in the series will be an introduction to the basic biology of evolution, and after this the series will move on to looking in greater depth at the cellular systems involved in cancer, and how tumours evolve.

This week Gordon Brown gave his cabinet a shuffle, after a bunch of his friends walked out on him. He managed to upset scientists twice. First he merged the department of universities and whatsits into the department of business and other stuff, only two years after giving universities and science their own independent department. Then he gave the minister for science, Lord Drayson, an additional job in charge of military research, prompting a sitting of Lord Drayson's question time from concerned scientists on twitter.

You already know why we are wary of science being put in the hands of those whose primary interests are business and war. There are enough reasons already, but I will add one more.

• 2008 NIH Budget: $29 bn ^[1]
• Cost of Iraq War so far: $677 bn ^[2]
• Bailout: $9,700 bn ^[3]

In Broca's Brain, the great humanist Carl Sagan dreams about what he could do with the $111 bn (adj $686 bn) that were thrown away, alongside 6 million lives, in the Vietnam War. He dreams of independent orbital cities, constructed from lunar andasteroidal material. It is the dream that we, the restless species, have had from the start. The dream of adventure and discovery. The technology developed in Sagan's dream would change the world, and provide abundant cheap solar electricity generation. But more importantly, we would have crossed the frontier. Our self-propagating city planetoids would host great discoveries, great progress, and, perhaps, the only chance for our species to survive itself.

History judges governments and civilisations by their priorities and achievements, their missed opportunities, and their downfall.

References

1. ^  Nature News (PDF)
2. ^  CostOfWar.com
3. ^  The real cost of the bailout and stimulus.

I wrote to my constituency MP. I've never done that before. I don't know if it's a useful thing to do, but it was fun. I guess it's slightly less pointless than voting.

Dear Tessa Jowell,

Given the evidently excessive use of force by the police during the "G20" protests at Bank three weeks ago -- not just from individual officers, but from the basic design of the police operation -- I am moved to add my voice to those who have expressed concern regarding police accountability, and specifically regarding provisions in the recent Counter Terrorism Act, which I understand you voted for.

Many -- most -- of the details of that day which have so far emerged are only available to us because the crowd was packed with press photographers, because London is populated by many tens of thousands of hobbyist photographers, and, most of all, because of the now ubiquitous cameraphone. This event highlights not just the need for police accountability, but the fact that it is ordinary members of the public who make police accountability possible. Any development which obstructs, or which could be used to obstruct, ordinary members of the public who find it their duty to record abuse of police power would be very disturbing.

I do not especially fear that the Counter Terrorism Act will lead to gross miscarriages of justice against professional or amateur photographers -- that is possible, but I suspect unlikely. Rather, the provisions in the act, by adding further complexity and uncertainty about what is and is not legal, enable the petty miscarriages of justice that have become rife and which make the police an intimidating presence in this city today. The cost of this law is the photojournalist who is obstructed from an important public-interest story while detained "under suspicion", the ordinary members of the public, and even tourists, who are stop-and-searched for engaging in their hobby (as I was in Crystal Palace park last year), and the photographer who simply gives up because the fun has been taking out of being creative.

Those costs must of course be balanced against the need to prevent terrorism. Since you voted in favour of the Counter Terrorism Act, I would be very interested to hear your own views on how the terrorism-fighting benefits of the photography provisions weigh against the costs, as well as the government's reasoning behind the provisions. How will these provisions help the police and prosecution service in catching and keeping us safe from terrorists? What evidence is there that these provisions would have helped to prevent past terrorist attacks, or to prosecute individuals who got away with committing atrocities?

I would perhaps not agree unconditionally with Benjamin Franklin's views on trading freedom and safety. But I must demand that we pay a fair price for the genuine article. In this case, as with many other laws supposed to protect us from terrorism, I am far from convinced that enough has been done to ensure that the prices will remain low and that we will receive the goods. I look forward to hearing your views on this law.

Yours,

Joe

I found on the iPlayer the latest in BBC2's series of Darwin documentaries, Did Darwin Kill God? This is theologian Conor Cunningham's attempt reconcile science and religion, and show that their differences are all just a misunderstanding deliberately promoted by 20th century American christian fundamentalists, and 21st century atheist fundamentalists.

We could play count the mistakes, but I'll try to keep it to the most illustrative examples. Firstly, Cunningham wants to show that Darwin himself has nothing to say on science versus religion. In correcting the simplistic idea that Darwin lost his religion entirely because of evolution, Cunningham suggests that Darwin instead lost his religion entirely because of the personal tragedy of his daughter's death. Uh. I think you'll find it's a bit more complicated than either of those. And it's true that Darwin did, for various reasons, generally try to keep quiet about God and religion, but he knew his work did have a bearing on the field, and, for example, made quips about a loving creator god and the design of parasitic Ichneumonid wasps.

Worryingly, it is not just his history of science that is oversimplified so far as to be plain wrong: his characterisation of his own field looks no better. He seems to think that throughout history creationism was an obscure aberration, taken seriously only by the eccentric fringes of theology -- you know, like James Ussher, mere Primate of All Ireland, or theologian William Paley. Real members of the One True Faith followed the "mainstream" teachings of Augustine, and took Genesis as allegory. I am not, and have no interest in being, a theologian. I don't know enough about the subject to be able to say whose ideas have attracted the largest following throughout history. But I am slightly concerned. In my experience, a theologian placing an idea on the fringe means that modern European academic theologians don't take it seriously, but that it has probably been the dominant dogma of their church and its laity for most of its history.

Meanwhile, Cunningham's idea that American creationism was invented during the Scopes trial as a reaction to eugenics is an entirely new one to me, along with the ideas that American creationism was all old-earth creationism until the 1960s, and that young-earth creationism was invented as a reaction to sixties liberalisation of values. Biblicalliteralists are indeed motivated by perceived threats to their moral systems, but I think you'll find that the history of the movement is a bit more complicated than that -- to the extent that Cunningham's version of history is just plain wrong.

The best part of the programme though, is Cunningham's attempt to characterise the state of current thinking in evolutionary biology, and show how "ultra-Darwinists" are discredited. Perhaps if I knew as much history and theology as I do biology my jaw would have dropped as far in those sections as it did in this one. The dropped jaw soon turned to laughing out loud, though, when I realised that the work was merely one of incompetence rather than deliberate misinformation. I'll skip over his bizarre attempt to introduce the selfish gene theory and how the human genome project has disproved it (!), and move on to the part that really had me rolling on the floor: one of the most fantastically absurd non-sequiturs I've ever heard.

The topic was memetics: the idea that ideas are replicating units that evolve as they spread from one mind to another. Memetics was originally just a thought experiment about hypothetical units of evolution analogous to genes, but was fleshed out, for example by Daniel Dennett and Sue Blackmore. Now, Sue Blackmore is great, but if Cunningham really knew the state of evolutionary thinking, he would know that she does not really represent even "ultra-Darwinists". But Cunningham drags her to Salisbury so that they can do an interview in the station car park. Brilliantly, he discovers a fatal flaw in the theory of memes -- one that he seems to think somehow has important consequences for the credibility of Richard Dawkins and the God hypothesis: if memes are true, evolution is itself a meme!

... so what?

Well, think about it. If evolution is a meme, it's just a parasite in our mind, and not true! Memes destroy the truth of evolution!

Uhm. But-

Ultra-Darwinists have never been able to answer this problem!

Oh ... kay.

Cunningham clearly really does truly believe that his brain has just done something brilliant. I suspect he is correct in stating that "ultra-Darwinists" have never been able to answer the "problem", since I have difficulty believing that anyone would ever before have managed to think of it and say it out loud before noticing what an utterly and humiliatingly ridiculous thing it would be to say.

As an aside, it is interesting to consider truth and memes. Under the theory of memetics, the idea that truth is of value would itself be a meme (and a very meritorious one). In the Selfish Gene, Dawkins talks about the need for genes to cooperate, or to put it another way, selfish genes have to be able to survive in an environment that contains many other selfish genes. Analogously, memes have to survive in an environment of other memes. Scientists, for example, host a series of memes for methods of filtering the non-true memes that might be trying to infect them. Skepticism, rationalism, logic, reason, and empiricism are memes that are also meme filters. But many people do not host them. Others fail to recognise the truth in a meme because it conflicts with false memes that they are already hosting. Some people do not even host the truth-valuing meme.

--

Cunningham's thesis -- and, it would appear from the website, the thesis of the executive producer of the BBC2 Darwin season -- is that creationists and "ultra-Darwinists" are extremists: two different kinds of fundamentalists abusing Darwin to promote their sinister agenda. Richard Dawkins, for example is an extremist because he believes that there is no need for God. (Not because he believes that religion is a bad thing: merely believing that there is no need for God is enough to get you branded an extremist.)

Cunningham is showing us the two unreasonable, frightening, even dangerous extremes, and telling us that the truth lies in the middle -- bang on the spot where Darwin and the Bible are both right, in their own ways. This is apparently the reasonable position. Life on earth evolves, and Christ died on the cross for our sins and rose from the dead. That's the reasonable, moderate, non-extremist middle ground position to hold.

Perhaps next the Beeb could help us reach a nice reasonable and moderate middle-ground position between those extremists who either demand that pi is ~3.14159 or that it is exactly 3.

A couple of passages which stood out in Clay Shirky's Here Comes Everybody.

On the kind of blogs that witter inanely about nothing in particular, or indeed which get tediously nerdy about an obscure topic that you don't want to read about:

"And it's easy to deride this sort of thing as self-absorbed publishing -- why would anyone put such drivel out in public?

"It's simple. They're not talking to you.

"We misread these seemingly inane posts because we're so unused to seeing written material in public that isn't intended for us."

I've always defended the right of other people to write blogs that I don't want to read, because there are many reasons to write a blog beside becoming a world famous trend-setting public intellectual. But I had never thought of it in these terms before. Web 2.0 means that a lot of people have to unlearn the basics of how media works pretty quick.

--

"Filter-then-publish, whatever its advantages, rested on a scarcity of media that is now a thing of the past. The expansion of social media means that the only working system is publish-then-filter."

Either this statement is wrong (or to be qualified with a great many exceptions to the rule), or a lot of people that I know are in denial. Like the ones who are convinced that experiments have demonstrated that post-publication peer review can never work.

--

Shirky also describes the case of scribes after the invention of the printing press. From our 21st century position we think of scribes as having some low-level secretarial role, just copying passages of text. But the profession was much more than that, and even after the invention of the printing press there were some who were confident that society could never survive without scribes. We no longer have people called scribes, but parts of their profession did indeed survive to some extent, in some of things that secretaries, journalists, academics, lawyers, and many others still do.

This is what is happening with journalism. You can bet that those who believe that journalism will survive as it is, because "society could never function without it", are wrong. Society does not need and will not continue to support what we call "newspapers" -- physical or online -- for example. But some of things that some journalists do will continue to be necessary and viable. Somebody will still be delivering those things in the future. We're probably not yet in a position to say which things will survive, who might be delivering them, or how they will be delivered, but we know some of things that will be in the mix -- including amateurs on blogs.

Christina Odone reviewed Bill Maher's film Religulous on Radio 4's Front Row (start: 9m).

"He gets some very good replies from some terribly soft targets." She's thinking particularly of creationist-sympathising US Senator Mark Pryor (D-AK).

She goes on, "... but the most revealing moment is when Maher faces down a priest at the Vatican and says, 'what about hell, what about sin, what about, you know, the evils of temptation?', and the priest says: 'yeah, what about them?' and kinda shrugs off this simplistic attitude that Mayer has."

And that's the problem with the film: Maher is attacking "the wrong target." What on earth attracts Maher to the simplistic belief of Mark Pryor, a mere everyday US Senator over the sophisticated religion of everyone's favourite heavyweight Latinist Father Reginald Foster? What has Pryor got to offer the world? What influence does he have over anything? Who cares if some boring politician in the upper chamber of the legislature of some great world superpower might be sympathetic towards ridiculous religious views? What matters is that Vatican astronomer Father GeorgeCoyne softly dismisses those ridiculous religious views as being no longer relevant to the modern church. I mean, do try to keep up, atheists.

And I mean, so what if some soft target like The Pope makes some sort of batshit insane remark about condoms that defies basic anatomy and psychology, spits in the face of everyone who gives a crap about basic standards of truth-telling, and adds further insult the injury of millions of devastated lives? Why attack a soft target like him? What harm could his remarks possibly do?

I was listening to an old episode of the SETI institute's podcast Are We Alone, in which they talked to a CSICOP (or whatever it is they call themselves these days) investigator. He described how he approached claims of the paranormal: he was neutral, and he �suspended disbelief� while he investigated the claim. He is not the only person to state that they �suspend disbelief� when looking at wacky claims. But he is wrong. He described his methodology in greater detail, and with case studies. What he is actually doing is following the stereotype ("type workflow"?) of the scientific method. In science, we make new hypotheses -- wacky or tame -- about how the world works, but it is assumed that the null hypothesis is true until we have evidence to suggest otherwise.

When reading a good novel, or watching a good film, we suspend disbelief. Not necessarily consciously -- we just slip away from the physical world into the story without thinking about it, and can instantly adjust back to the real world when we pull out of the tale. That's not the sort of belief suspension that is going on when we investigate claims of the paranormal. When investigating anything one has to keep one's wits about one. If Sherlock Holmes suspended disbelief and just listened to the tales of witnesses he would never solve a case. Holmes' greatness comes from his careful analysis of every minute detail that he is given, his sharpness at spotting the questions that need asking, and his refusal to take the word of others for granted -- to poke around for the weak spots in what he is told.

If you are suspending disbelief when considering truth-claims, you're doing it wrong. Truth-claims should be the subject of skepticism. Skepticism is a good thing. It is not close-mindedness. It is not cynicism. Skepticism is staying alert and active in the investigation. Skepticism is the doorman of your mind, checking who is coming in, and ejecting the riff-raff. The doorman doesn't bar everybody, he just asks a few basic questions to keep out the fakes, mistakes, and frauds. Skepticism is processing the information coming into your mind. Without it, you can't solve a case, answer a question, discover the truth.

--

As Derren Brown notes, there are some situations where we know what is and what is not. Sometimes we know when a claim can be dismissed as laughable. Some claims are so clearly illogical, irrational, or impossible, that their falseness is instantly recognisable. When a hippy makes a baseless proposal that contradicts what we know about the way the world works, keeping an open mind or opening an inquiry is not a productive use of your time and skills. We are allowed then and there to make a judgment on the hippy's absurd ideas, without denying that all knowledge has an element of provisionality . Saying that one is "keeping an open mind", suspending judgment, and investigating the possibility that the claim is true is meaningless posing.

And yet so many intelligent people adopt this pose with god.

The past few weeks seem to have seen laments for the decline of journalism and obituaries for old media reaching a critical mass. BoraZ has kindly collected a few dozen so that I don't have to.

Perhaps it's just because I've been reading Nick Davies' Flat Earth News, and because Davies did the last Skeptics in the Pub, that I have been noticing that the decline of newspapers is reaching this critical stage. Davies is a Guardian investigative journalist, and he's breaking the rules by telling us just what a state the media is in. Flat Earth News, written two years ago, before the American newspapers started going bankrupt, and British newspapers shed half their workforce, documents the many multiplicative flaws in the system of news gathering, reporting, and dissemination which cause journalists to churn out the crap the passes for newspapers these days.

Davies' conclusion is that journalism -- a noble profession of bright people -- has, largely as a cost-cutting measure, been reduced tochurnalism . Instead of spending a week researching a story in great depth and telling us the important facts that we didn't know, journalists have been reduced to rewriting a dozen wire stories and press releases each day. Journalists no longer have the time, the background knowledge, or the luxury of specialisation, required to find out whether the words they are writing bear any resemblance to reality. Nor do they have the time to establish what conflicts of interest of their sources have and whether they are hiding things -- instead, the words can be reported as he-said/she-said, and the report can technically never be wrong.

Indeed, the media and public relationships industry have evolved a sophisticated mutualistic relationship. Newspapers could not fill their papers without press release writers doing all their research (and even choosing their words) for them, and in return, interested parties get their side of the story, or their product, prominently placed in the story.

M'colleague suggested that this thesis sounded a little like a conspiracy theory. I, however, am generally convinced. I am convinced because I have seen it work so many times in the field that I am familiar with -- science and medicine. I have seen how the British tabloid (and even broadsheet) newspapers build their oncological ontological database from poorly written press releases. I have seen how interested parties both in industry and pressure groups place their doubt or certainty in news stories about the environment. I've seen the basic failure of fact-checking as elementary mistakes in press releases about newly published journal papers are faithfully replaced in all papers. I've even seen my own words from Wikipedia appear in The Metro's obituary of John Peel. And I've seen how successfully our own side has fought back on the media's own terms, when Sense About Science press released their detox dossier in the slow news week after Christmas.

Flat Earth News provides the overarching explanatory theory for why so much of the news media is, to quote a comment on Friday's Ryanair-toilets "news story" publicity stunt, "such a great lorry load of cock." Science bloggers like a good whinge about a bad science or medicine story in the paper, but the problem is much greater than just a few humanities graduates trying to write about science. That skepticism you apply when reading the science stories needs to apply to the politics, foreign events, business, and everything else besides, because the authors of those items know no more about their subject than the humanities graduates covering science do about theirs.

Journalists can cry that democracy is not possible without them; but there's nothing empowering about a media that churns back the press releases of government departments and military agencies. There is nothing empowering in the Daily Mail.

Somebody said something rather odd the other day. It was in response to the observation that I know a great many scientists and mathematicians who are also amateur photographers. Their suggestion was that photography was a good way to express one's creative side.

Now, there are a few dozen photographs in my collection that I'm particularly happy with. They are technically competent and have a modicum of aesthetic value. But if they demonstrate creativity is is of the most trivial variety, and in pitiful quanta. That is not to say that photography can not be creative; only that amateur photographers rarely display any significant quantity of it. We create images that have been created before, follow formulas and fashions, and imitate each other's styles. And so what. Amateur anything -- painting, poetry, music and sport -- is about having fun, not about creating world changing work.

Science, on the other hand, has everything to do with creativity. A scientist's job is to replace a package of ignorance with a package of knowledge. Scientists do not create facts -- a task so simple that it is left to the science-fiction writers. Rather, the facts are already there, waiting to be discovered. The task of the scientist is to create the hypothesis -- to ask the question so out-there that nobody has ever thought to ask it before -- and to create the experiment that will test it.

The achievement of Watson and Crick -- determining the structure of DNA -- is often derided by those who rightly wish to celebrate the achievements of Rosalind Franklin. Franklin performed many of the difficult experiments whose results were crucial for determining the structure of DNA. According to some, Franklin was doing clever physics and chemistry while Watson and Crick were playing around with toy molecules. Watson and Crick did eventually get the structure by building a model, with a small amount of trial and error involved.

In reality, Watson and Crick got to the model by being creative. They created ideas and hypotheses from data such as x-ray crystallography and knowledge like nucleotide ratios and properties. They had the creative idea to have the toy molecules built and to cut out the tedious and time consuming experimental work that would be required to fill the remaining gaps by simply trying out variations until they found the one that worked.

Nobelist Harry Kroto does not feel like a great scientist because he doesn't know everything. He enjoys science, but thinks that all he is any good at is designing logos and posters. Harry: your designs are, ah... nice. But your science is where you are creative. And that is why you are a great scientist.

Bugger knowing everything. What fun would science be then?

I found a moment to read Edzard Ernst and Simon Singh's Trick Or Treatment. Ernst is professor of complementary and alternative medicine at Exeter University, and he applies the methods of science and evidence-based medicine to so-called alternative therapies. In this volume, Ernst and science-writer Singh review the evidence base -- or lack of -- for some popular (UK-centric) alternative medicines. It's what you would expect from such an undertaking: a series of chapters along the lines of "[ homeopathy | acupuncture | chiropractic ] (delete as applicable) is supposed to work by ................... (insert magical and demonstrably false hypothesis about how biology, chemistry, or physics is supposed to work). It doesn't." This is followed by a chapter on why CAM is unethical , including for example, why CAM is usually a scam based on arbitrary and discredited unscientific foundations, and why real doctors are wary of lying in order to take advantage of the placebo effect.

One chapter was different: a collection of notes on "herbal medicines". This chapter covered a whole class of treatments, and it concluded that some of them have some value, most of them have no value, and some of them are highly poisonous. This is hardly surprising: many (most?) of our pharmaceuticals are based on (that is, safer and more effective derivatives of) nature's designs: the chemicals produced by plants, and other branches of life. There's still a lot of magical, irrational, and plain wrong thinking associated with herbal remedies, but that doesn't mean that believers can't chance upon a correct idea once in a while. Stopped clock, twice a day, etc.

The general conclusion is that, other than a few herbal remedies, CAM treatments are useless, based on laughable pseudosciences, and are sometimes dangerous. Either they have been demonstrated to have no effect, or studies have failed to show any significant effect. A recurring theme is that studies and trials in CAM tend to be performed incompetently by people who either don't know how to perform research properly, or who know that if they did it right, they wouldn't get the answer they want. (The authors are too polite to put it quite so bluntly.) So since CAM is so widely used, some of it may be useful, and there may be hidden (and not so hidden) dangers, further research is necessary to make up for the shortcomings of the current body of literature. (Of course, academics have to say that about their fields as often as possible these days.)

I don't buy it. Why is further research necessary? There are a select few cases of herbal remedies where further research might not be a waste of time -- you can tell by the fact that, in addition to public institutions , pharmaceutical companies are doing that research. But for everything else, this is just money down the drain -- money that could be spent finding real ways to save and improve lives. Homeopathy, chiropractic, and acupuncture not only fail under the inevitable stacks of negative evidence, they, like most of CAM, suffer the provenance flaw. The supposed mechanisms of these "remedies" were just conjured from the air; and they often contradict what we already know about how the human body, chemicals, and the physical world work. There is simply no reason to think that such absurd fiction might turn out to be true.

When something has a provenance flaw, you can't just say "further research is necessary." I could invent an unlimited number of baseless hypotheses -- in the same way that homeopathy, acupuncture, and chiropractic were conjured -- and, surprise, further research would find only that none of them have any merit. Picking your nose gives you cancer, chocolate digestives cure Alzheimer's, my dad invented space travel, Mornington Crescent Station is really a top-secret government intelligence headquarters, and Stephen Fry is a time-travelling robot controlled by aliens. Further research on these topics is necessary; cheques payable to Joe D, please. No? How about if I first get a few tens of thousands of people to believe in my bullshit?

This is why the new US administration should defund NCCAM.

In which I complete one project and promptly commit myself to more hard blogging...

Cancers evolve. That's something that I hope to show you over the course of a couple dozen posts -- "a landmark new series," as the BBC would describe it. I'd like to show you why and how cancers evolve, how the evolution of cancers compares to the evolution of populations and species, and also discuss the adaptations that tumours commonly stumble upon. There will be genetics, genomics, molecular, cellular, developmental and systems biology, amongst medicine, surgery, and pharmacology. There should also be a few tales of how the science was done, and who did it.

The first two posts will describe the very basics -- an easy catch-up course for those unfamiliar with biology. Those who already know their oncogenes and tumour suppressors, cell-cycle checkpoints and DNA-repair pathways, can skip the first. Those with a basic grasp of evolution, from the point of view of genes, individuals, populations, and environment, can pass on the second.

Later, half-a-dozen or so posts will look at the details of cancer evolution: the micro-environment of the tumour, and the selection pressures it produces; how tumour evolution looks in terms of population; tumour cell biology, and the Knudsen multi-hit hypothesis; cancer cytogenetics and chromosomal instability; controversial hypotheses of cancer "stem cells"; and cancer epigenetics.

Then there are the adaptations that we see in cancer, why we see them, and how the biology is of relevance in diagnosis and treatment. We'll discuss, over a number of posts, loss of DNA checkpoints and repair, disregulation of cell growth and division, loss of cell death, gain of anaerobic respiration and the raiding of sugar stores, new blood vessel growth, evasion of the immune system, invasion and metastasis, and finally drug resistance.

So join me in a celebration of the simple principles that Darwin discovered in the 19th century, and which save lives in the 21st.

This post is part of a series on The Origin Of Species.

There are those who declare Darwin's literary brilliance, and those who proudly announce that The Origin is beyond their wit and attention span. Occasionally, the truth may be found between extremes: reading The Origin has been frequently fascinating, occasionally a joy, and not infrequently tedious. Chapter 15, however, is nothing but a delight.

Darwin recapitulates his "one long argument", putting together a brilliant persuasive case. He starts with the objections to common descent and natural selection, admitting that he has "felt these difficulties far too heavily over many years", before reminding us where the objections fail. Throughout the book, Darwin has made few references to the alternative ideas on the origin of species that had been proposed during his time, but in chapter 15, he openly mocks them: "how inexplicable on the theory of special creation is X, Y, and Z;" "do they really believe that at certain innumerable periods in the earth's history certain elemental atoms have been commanded suddenly to flash into living tissues?;" "mammals: were they created bearing the false marks of nourishment from the mother's womb?"

Meanwhile, he constantly reminds us of the power of evolution: "how simply explained X, Y, and Z are on the theory of common descent;" "innumerable other facts at once explain themselves;" "we may cease marveling, and understand on this view...". He reminds us of some of the many otherwise inexplicable quirks of biology that he can shed light on: his "specific characters"; the honey-bee's comb; the neuter insects and their social structure; the geographic distribution of species; the structure of different genera; the homologous bone structures of the human hand, bat wing, and porpoise fin; the identical number of vertebrae in elephant and giraffe necks; the branchial slits of mammalian embryos. "It can hardly be supposed that a false theory would explain in so satisfactory a manner as does the theory of natural selection, the several large classes of facts above specified."

This is the sixth edition of The Origin, and by now Darwin can allow himself a moment to bask in some glory. By the time he got to the sixth, "almost every naturalist now accepts the great principle of evolution," with only a few old dissenters stuck in their ways. And, knowing how powerful the theory is in explaining the items on his list of quirks, he knows that it will revolutionise biology -- "a grand and almost untrodden field will open up" -- and even notes how it applies to neighbouring fields like psychology. "Much light will be thrown on the origin of man and his history." And, in the knowledge that he has made a contribution to science as great as that of Newton, he goes out with the famous bang.

"There is grandeur in this view of life, with its several powers, having been originally breathed into a few forms or into one; and that, whilst this planet has gone cycling on according to the fixed law of gravity, from so simple a beginning endless forms most beautiful and most wonderful have been, and are being, evolved."

-or- "(One of many reasons) Why genomics matters"

In chapter 14 of The Origin Darwin discussed embryological stages and their utility in classification. This utility derives from the fact that in animals phenotypic variation between species is less complicated at earlier developmental stages, and less influenced by what Darwin calls �special habits�. In some cases, this principle can be taken to extremes. Today, we refine species classification using the gold-standard method of comparative genomics. Comparative genomics involves matching up the As, Cs, Gs, and Ts of orthologous sequences (that is, sequences related by descent in now separate species) and highlighting where the genes have diverged. But sometimes, the most interesting finding is where the genes have not diverged.

The genomes of animals are stuffed full of sequences which have no obvious purpose, and in which mutation seems to be able to run free without consequence. Over evolutionary time, these sequences are buffeted by random processes, and as species diverge, so these sections of their genomes drift apart. Buried in amongst all of this nonsense, though, are functional sequences, including genes. In these functional sequences, mutations and variation might have all sorts of phenotypic consequences, and genomic variations which have consequences can be subject to selection. There is a tendency, therefore, for such sequences to show very different patterns of variation between species to that of the �junk� sequences. These patterns can reveal important principles in biology, and the patterns themselves are discovered by comparative genomics.

One of the most notorious finds is the homeobox motif.^[1] This motif is a gene-subsection found in a set of genes called Hox genes, and it has the rare distinction of being found in such distant groups as vertebrates and insects with an almost identical sequence � it is therefore said to be highly �conserved�. The sequences vary only in that they contain �silent mutations�. Due to the redundancy of the �genetic code�, which maps the 64 possible triplets of nucleotides � gene letters � to the twenty commonly used amino acids � protein letters � many mutations within genes will make absolutely no difference to their carrier's phenotype, and thus go unnoticed by selection. Such mutations are said to be "silent". Darwin may have been interested to learn that the Hox genes, which contain this famously conserved motif, happen to be key in determining the layout of the body early in development. There is genetic conformity to match the phenotypic conformity in early development.

But the sequences encoding proteins are not the only important functional sequences in the genome. There are plenty of sequences associated with genes � regulators of gene expression, for instance � and a few interesting things that are not associated with genes at all. �Cis-regulatory regions�, for example, are found beside genes, and contain sequences which enable enzymes to attach themselves to the DNA and initiate gene expression. During the past decade, interesting patterns of conservation have been discovered in the cis-regulatory regions associated with many genes, and especially with key developmental genes. These cis-regulatory sequences do not directly map to protein sequences, and so they can not contain �silent mutations� in the sense that protein coding regions can. But these sequences can be conserved. They can be very highly conserved. They can be ultraconserved!^[2][3] Sanderlin, et al found in 2004, for example, �ultraconserved� cis-regulatory sequences over 1000 bases in length which were identical in human, mouse, and pufferfish, and over 3,500 perfectly identical regulatory regions of 50 bases or more.^[4] Those numbers might mean nothing to you, but the bottom line is that if genomes were essays, somebody would be in front of a plagiarism tribunal right now.

In BMC Evolutionary Biology, last year, Lin et al^[5] described a novel collection of ultraconserved regions (UCRs) that they stumbled upon in the Hox genes of placental mammals. These particular UCRs were not found in the cis-regulatory regions, but are the first to be found in the protein-coding sections of genes. The URCs are at least 125 bases in length, and are identical in humans, dogs, and mice � indeed, they actually show a greater degree of identity in these species than does the famously conserved homeobox. Lin et al can not yet explain the importance of the UCRs that they have found, but it is reasonable to assume that important they must be. The thing I find particularly interesting about their story, however, is how the UCRs were found and investigated. Lin et al stumbled upon the conserved regions while looking at a different question � the divergence of Hox genes in mammals. They had retrieved the sequences of orthologous Hox genes for mammalian species such as human, chimp, cow, dog, duck-billed platypus, macaque, mouse, opossum, and rat, along with chicken, pufferfish, and zebrafish for comparison. These are all species whose genomes have been sequenced and made publicly available in government funded databases. Lin et al used a clever search engine called BLAST to find all of the Hox genes of these species, and then used a classic piece of bioinformatics software, ClustalX, to �align� all of the genes and point out where they do and do not vary between the species.

Why do I get excited by BLAST and ClustalX, the workhorses of computational biology? Because it's little studies like this which serve to remind us of why genomics and computational biology are important. Genomics it seems has still not recovered from accusations of being overhyped after the biotech bubble burst a decade ago; and computational biology gets all kinds of slander thrown at it � a discipline churning out unreliable results to be dismissed, or a field to turn to in desperation as laboratory studies refuse to give you the answer you want. Perhaps, when you've slaved for years as a student and had to fight for the funding to maintain a laboratory, there is something a little frightening about research that requires just a PC, an internet connection, and a clever idea. But Lin et al discovered a whole new category of ultraconserved genomic regions right under the noses of the hundreds of molecular and developmental "wet" biologists who work on these hugely important Hox genes, using just some everyday software, the bulk raw data of genome projects, and the wit to spot an interesting pattern.

BLAST and ClustalX are exciting because with just a sequence alignment, you can demonstrate again and again, in an almost endless variety of ways, just how right and how powerful the theory of evolution is.

References

1. ^  Woltering J, and Duboule D: Conserved elements within open reading frames of mammalian Hox genes. J. Biol. 2009 8:17. doi.
2. ^  Dermitzakis ET, Reymond A, Antonarakis SE: Conserved non-genic sequences � an unexpected feature of mammalian genomes. Nat Rev Genet 2005, 6:151-157.
3. ^  Bejerano G, Pheasant M, Makunin I, Stephen S, Kent WJ, Mattick JS, Haussler D: Ultraconserved elements in the human genome. Science 2004, 304:1321-1325.
4. ^  Sandelin A, Bailey P, Bruce S, Engstr�m PG, Klos JM, Wasserman WW, Ericson J, Lenhard B: Arrays of ultraconserved non-coding regions span the loci of key developmental genes in vertebrate genomes. BMC Genomics 2004, 5:99. doi
5. ^  Zhenguo Lin, Hong Ma, Masatoshi Nei (2008). Ultraconserved coding regions outside the homeobox of mammalian Hox genes BMC Evolutionary Biology, 8 (1) DOI: 10.1186/1471-2148-8-260

Disclosure: I work for the publisher of three of the journals cited, and handled one of the papers (Lin, 2008). All opinions are my own, this post was written on the train, not in the course of duties, no privileged detail that can't be found in the paper was disclosed, etc, etc.