Is it a cancer drug or not?

The media faces constant criticism from medical specialists and  advocacy groups whenever it trumpets the latest new wonder drug to cure any form of cancer.

Many spurious claims have over the years been splashed across the UK Daily Mail’s front page, prompting backlash from organisations such as the National Health Service, Cancer Research UK and even the appearance of a Facebook group with more than 40,000 members criticising the Mail’s cancer cure/cause agenda.

But the recent news that pharma giant Roche was revising its position on Avastin after the drug failed in a late-stage study, evaluating the blockbuster as a treatment for advanced stomach cancer, was an example of where the stock market, media expectations of a miracle cure and a pharma giant collided.

The Wall Street Journal said the announcement had the effect of:

‘undermining market expectations the drug could reach annual peak sales of more than eight billion Swiss francs ($7.48 billion)’

Roche’s PR team has had the very difficult job of trying to push the share price back up and regain investors confidence. One of their newest stabs at this crisis communications was a release today stating that

‘the eyesight of two patients with a rare condition was saved through the groundbreaking use of the drug Avastin’

At the time of writing, the news is only 20 minutes old so and there is little detail contained on how many people have been involved in trials by Southampton ophthalmologist Dr Andrew Lotery, only to state that his research on treating Sorsby’s Fundus Dystrophy (SFD) has been accepted by US journal Retinal Cases & Brief Reports. The release goes on:

He (Lotery) said it was the first time the drug had been used to treat the rare genetic condition(SFD) which caused the two patients, both in their 30s, to suffer blurred vision and a general deterioration of sight.
Avastin halts the growth of blood vessels and stems bleeding and is commonly injected with good results into the eyes of patients with “wet” age related macular degeneration (AMD) – the leading cause of blindness in the western world in people over 50

Avastin has already been trialled successfully in conjunction with chemotherapy in ovarian cancer sufferers so the prospect of another potential target would be welcomed by the shareholders but more importantly, by sufferers of the targeted conditions. But this is a situation where the media needs to tread carefully and wait for stronger research to appear before latching onto another cure-all drug.

New antibiotic treatments for gastric cancer

On another cancer story, Yoshio Yamaoka, an F1000 Medicine faculty Member from Japan, has looked recently at the use of various drugs to treat Helicobacter pylori infection, which often leads to gastroduodenal ulcers, gastric cancer and associated diseases.

While there are positive signs from a large multicenter trial in Japan of H. pylori antibiotics on patients with gastric cancer, Yamaoka warned that practitioners should exercise caution with regard to widespread antibiotic treatment saying,

‘if all infected persons are to be treated, we should consider the increase in frequency of antibiotic resistance and unexpected consequences such as esophageal adenocarcinoma, asthma, and autoimmune disease’

Hair apparent

beware of the bearded man bearing breadfruit

Sometimes there’s a real life-changing thrust to blog posts, that drives at the heart of a pivotal issue in modern society and make people question their motives, passions, opinions or even educational goals.

But seeing as we’re all coming down off a post-Oscars high, let me preempt your own judgement by rating this one as an Inglourious Basterds compared to the Hurt Locker of more worthy blog scribblings.

Actually, it’s really more of a Valkyrie than QT’s latest effort but then Tom Cruise never won any awards for his ability at copying accents (and it obviously wasn’t nominated for the 2010 awards so it’s less zeitgeisty).

Anyway, my point is to direct your eyes to the picture of the man on the left, much-respected Stanford neuroscientist and f1000 Faculty Member Robert Sapolsky.

With a beard that would make Hagrid feel ashamed, Sapolsky must be a delight as a lecturer. He’d also make a great magician with no need for a top hat either.

Sapolsky is a seasoned reviewer for f1000 and contributed a very positive review of a recent paper in Nature which discussed Prejudice and truth about the effect of testosterone on human bargaining behaviour. The crux of the paper was in a press release we put out today but the first emailed responses from journalists focused not on the weighty issues being discussed but of course, the accompanying photo above.

In one reporter’s words, it encouraged her to ask for more information on him as “I’ve been meaning to do somethign (sic) on weirdy beardies for a while”.

This is not the first time we’ve discussed hirsute scientists and our friend Joanne Manaster has a similar penchant (purely scientific) for bearded biologists. But it reinforces once again how much we should respect a scientist who sports this look: if he shows half as much commitment to research as to beard growth, a cancer/malaria/Xbox-related RSI cure is surely not far away.

*it’s ok, I cringed while writing the headline as much as you probably did reading it. To me it felt like the title for a bad 90s C-grade comedy starring a faded stand-up comic.

Then I did an IMDB search (I’m writing this in real-time, so the punchline could be a fizzer) and whaddya know?

It was closest in wording to a bad Canadian comedy flick , a 1912 black and white romantic drama and best of all, the ridiculously titled, Michael Flatley: Eire Apparent, about the most arrogant Irishman to ever pull on a pair of tights. Riverdance fans, I’ll meet you in the car park if you want to take issue with that assessment.

The drugs don’t work

A copy of ‘People & Science’, the publication of the British Science Association appeared on my desk this morning. (Aside: what is it with these people? Founded in 1831, they used to be known as the British Association for the Advancement of Science, or the BA, and set out to combat the perceived elitism of the Ri. Fair enough, but they had a massive re-branding exercise last year and now have a logo that looks like a bilberry splat. Failing to learn from the experience of CRUK, they also object to the abbreviation BSA, which depending on preference is either related to blocking agents or motorcycles. At least BAAS got them on the front page of Google, even if it does sound like sheep shouting.)

Anyway, the article flagged for my attention is one by Sir John Krebs, son of the famous German biochemist Hans (of Krebs cycle fame) and a frighteningly distinguished scientist himself. Krebs, who chaired the 2007 working party of the Nuffield Council on Bioethics to produce a report on the ethics of Public Health, writes about the infamous ‘Nutt-sacking’. For those of you not up to date on the machinations of the UK Government, Professor David Nutt was chair of the independent Advisory Council on the Misuse of Drugs (ACMD), until he was sacked for, um, advising the government.

It’s not quite like that of course: the UK Government asked for advice on the classification, and thence the penalty for possession or trading, of cannabis. Based on evidence of potential and actual harm to individuals and society, the ACMD said that cannabis should remain a ‘Class C’ drug; that is possession should carry a maxium two year gaol sentence (compare with Class A drugs like LSD or heroin, carrying a seven year sentence for possession; and amphetamines, which carry a five year sentence). The UK Government ignored this expert advice and reclassified cannabis as ‘B’ (somebody should tell them about the Netherlands). The Prime Minister, even before the ACMD review, had already said that cannabis should be reclassified as ‘B’, and the then AMCD Chair, Sir Michael Rawlins asked the Prime Minister to butt out and wait for the review. When the review came around nobody should be at all surprised that the Labour Government ignored the advice (in the interests of populist policy and Nanny State-ness, no doubt). They had, after all, previously telegraphed that they had no intention of accepting the ACMD’s advice on the classification of ecstasy. As Lord Krebs says, ‘it would appear that the personal opion of the Home Secretary trumped the considered analysis of the statutory expert committee’. So, perhaps, the government should not have been surprised that Professor Nutt then publicly criticized them for ignoring advice.

They sacked him anyway. You can read some measured analysis from Bill Hanage, an epidemiologist at Imperial College, at the LabLit blog. Bill also lambasts politicians of all colours for failing to grasp that evidential science doesn’t give a hoot for policy.

Lord Krebs in ‘People & Science’ this month tells us that—however much we scientists might like to believe otherwise—independent scientific advice is, on the whole, valued in Westminster. Politicians of all parties are keen to emphasize their commitment to evidence-based policy, and in areas from infectious disease, to GMOs, to climate change, this commitment is usually fulfilled. There are over 70 expert committees providing advice and most Departments (but not, notably, the Treasury) have their own Chief Scientific Adviser. Lord Kreb’s own advice on the need to gather more evidence before deciding whether or not to cull badgers was accepted (but it would appear that didn’t make any difference in the long run—they eventually bowed to uninformed pressure from the farmers, presumably while P&S was in press); and the BSE crisis was handled on the basis of scientific evidence. He does, however, point out that it would have been better to assemble proper evidence before splashing half a billion quid on the Sure Start programme, but I guess you can’t win them all.

The latest example of politicians actually listening to scientists came just last week, when MPs from the House of Commons Science and Technology Committee said homeopathy ‘remedies’ are a waste of money, and should not be available on the NHS.

However, whether ministers will take heed of evidence that contradicts favoured policies, or apparent vote-winners, is still a matter of debate. The draft Principles on Scientific Advice published by the science minister Lord Drayson apparently emphasize the importance of independence, openness and respect for scientific evidence. But how are disputes going to be handled? And when Westminster ignores scientific advice, what recourse do we have? And surely, shouldn’t we be able to criticize elected representatives without fear of losing our jobs?

PS Prof. David Nutt is talking at the Science Media Centre on Thursday 18th March. I’d love to go but I’m going to Geek Pop The Science Sessions instead. More on that later.

More food for thought

By Steve Pogonowski and Bea Downing

Work dramas, late bills, latent childhood trauma: adult life is full of potential for the average person to get stressed and deal with it by ‘comfort eating’.

As discussed in a previous post by Callum, labeled ‘Food for thought’ (hence my segued sequel/blatant rip-off title here), there are ongoing studies starting to appear in the earlier pages of top-ranked journals that look at the psychological, rather than purely physical, causes and effects of weight gain and obesity.

But the fact remains that there is still much to learn about the biological processes resulting from the mental stresses of daily life.

In a recent F1000 Biology Report, Faculty Member Achim Peters from the University of Luebeck and Dirk Langemann of Carolo-Wilhelmina-University looked at recent advances detailing how stress affects neurometabolism and eating behavior.

Stress increases the brain’s demand for glucose and, in some people, causes comfort eating and weight gain due to a weak sympathoadrenal response.

Under stress, the brain’s metabolic rate – and glucose demand – shoots up by 12%. Two mechanisms then come in to increase glucose availability to the brain: brain-pull and storage-push. Brain-pull mechanisms increase the percentage and amount of energy that the brain can withdraw from the blood across the blood-brain barrier, while storage-push mechanisms increase blood-glucose levels to flood the system with energy.

During periods of chronic stress, the stronger storage-push response results in the blood being loaded with energy. When the brain’s demand for glucose falls, the storage-push is still releasing glucose into the blood. The remaining glucose is mopped up by insulin and stored as fat.

Peters and Langemann said:

“Evidence accumulates that the stressed mind can choose a metabolic coping strategy by switching its supply mode from brain pull to ‘comfort eating’.”

Chronic stresses in adult life, such as job-related demands and difficulty paying bills, may weaken the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. In adults with depression and anxiety, weight gain and the risk of obesity were increased in a dose-response fashion with the number of episodes of these common mental disorders.

Problems can also strike earlier in life: early-life stress and juvenile trauma result in long-lasting changes in the activity of the autonomic nervous system and body weight. Prenatal psychosocial stress exposure is associated with hyperinsulinemia in later life, a strong predictor of weight gain and a typical marker of brain-pull inefficiency.

On the run-12Feb10

Cancer Causes Cancer!

Well, that was the headline we should have gone with. It is of course a hat tip to the Daily Mail, a tabloid publication that is desperate to tell the UK population that just about everything causes cancer. (I found that website by googling ‘cancer causes daily mail’, which is in itself quite a neat headline. Unfortunately I think we’re closer to curing cancer than curing the Daily Mail. Oh well.)

So, we know that tumours have this nasty habit of sending out malignant cells into the rest of the body. They break off from the primary site and get into the blood and lymphatic systems, occasionally washing up in convenient organs where they can settle down and create new tumours, or metastases. This is partly why cancer is so difficult to cure: you can cut out the original malignant growth, zap it with X-rays and take all sorts of evil drugs (‘evil’ because they are designed to kill cells, and you’re made up of cells; and discrimination between the cancer cells and normal cells is a huge problem); but if one metastatic cell survives, you have to start all over again. And if it’s managed to find a home deep in a bone, or the brain, or somewhere equally inaccessible, it’s game over.

It turns out things are even worse than that. Circulating tumour cells, if they find their way back to their original ‘home’, can actually stimulate growth of the original cancer. Nasty. As the authors say,

Tumor self-seeding could explain the relationships between anaplasia, tumor size, vascularity and prognosis, and local recurrence seeded by disseminated cells following ostensibly complete tumor excision.

‘Ostensibly complete tumor excision’—that’s right, because no matter how good your surgeon is, you can never be sure you’ve cut every last bit out; or that some cells haven’t already gone walkabout.

The good news is that certain cytokines derived from the tumour, IL-6 and IL-8, act to attract the circulating cells, and that they get back in via the matrix metalloproteinase collagenase I (MMP-1) and fascin-1 (it’s the actin cytoskeleton again! These guys get everywhere). If we can find a way to selectively block these pathways we should be able to start thinking about appropriate therapeutic approaches. Gentlemen (and ladies), start your (grant-writing) engines.

Kim, M., Oskarsson, T., Acharyya, S., Nguyen, D., Zhang, X., Norton, L., & Massagué, J. (2009). Tumor Self-Seeding by Circulating Cancer Cells Cell, 139 (7), 1315-1326 DOI: 10.1016/j.cell.2009.11.025

Twitter storm

It’s been pretty hectic on the twittertubes this week. Following a random conversation at the Scholarly Kitchen I suggested writing papers in 140 characters would be a wheeze. I turned it into a competition, and we had an amazing response. Check back on Monday to find out who’s the lucky winner of a bag of f1000 swag.

Badger Wars

I don’t have a lot to say about badger culling to prevent/reduce bovine TB (except maybe to say that killing vermin with a high-powered rifle and decent ‘scope is one of the most humane ways of doing this).

I just like the sound of a ‘randomized badger culling trial’. Oh, and when someone ‘explains’

This trial was undertaken in very specific circumstances and it could be misleading to extrapolate the findings to any future control program.

you can be pretty sure there’s a vested interest or extreme prejudice somewhere. Even when the trial shows that there’s no economic benefit.
Jenkins, H., Woodroffe, R., & Donnelly, C. (2010). The Duration of the Effects of Repeated Widespread Badger Culling on Cattle Tuberculosis Following the Cessation of Culling PLoS ONE, 5 (2) DOI: 10.1371/journal.pone.0009090

Valentine’s Day

Just a reminder to all you chaps out there—it can’t hurt to buy some flowers, even if you don’t want to buy into the whole commercialization thing. A nice dinner doesn’t cost you much either, and could pay dividends in the romance stakes. But at the very least, show you really care by getting checked out:

Take a test for #Valentine‘s Day. Sexual health appointments across Lincolnshire within 48 hours. Call 01522 539 145

It gets pretty lonely up there in Lincolnshire. Have a good weekend, and I hope it’s full of lovehearts and kisses. Failing that, a beer or three can have much the same effect.

Adrift in an ocean of trash talk

My lesson for today: Don’t argue with an oceanographer over our responsibility for cleaning up the Great Garbage Patch. Actually, don’t argue with an oceanographer over anything marine-based and also don’t call someone (the inspirational Annie Crawley) an oceanographer who isn’t.

Credit: Slate Magazine

I made the mistake of saying that an article in Slate by Nina Shen Rastogi was wrongly titled, as I believed it should be asking how we can clean up the patch, not WHETHER we should bother.

Chief scientist Miriam Goldstein from Seaplex (@seaplexscience on Twitter),  which is The Scripps Institution of Oceanography/Project Kaisei expedition to measure plastic in the North Pacific Gyre, replied:

Actually I agree w headline. Open-ocean cleanup EXTREMELY expensive/technically challenging. Need to carefully consider cost/benefit.

The humbling part wasn’t in being dissed in under 140 characters for my lack of knowledge but in seeing what the important issues are when it comes to a massive area of trash that can’t just be cleared up with a few sweeps by a barge.

Like the Slate article author, I imagined the patch as a large mound of floating rubbish, spinning endlessly whirlpool-style without the plughole to drain out of. I had read of  banking fortune heir David de Rothschild’s headline-grabbing voyage on a yacht made of reclaimed plastic bottles, taking in the North Pacific Gyre on a route from San Francisco to Sydney (a project delayed partly by the extremely ambitious task of building such a boat).

But changing the concept that the Patch really isn’t a Patch at all will take some undoing. Perhaps there’s a word in another language that would better do it justice (and one not so similar to those of cute 80s dolls would bring home the message better anyway).

As Miriam said, cost and benefit are obvious considerations when looking at possible clean-up efforts. As Rastogi said in Slate, “despite the oft-repeated claim that the Great Pacific Garbage Patch is “twice the size of Texas,” we don’t really know the exact size of the Patch or how much garbage it contains.” (To Americans, Texas must seem really large: to Canadians, Australians, Russians etc it’s kind of small).

So committing x billion dollars to cleaning up an area of unknown mass and size could be essentially fruitless. Commenters on the article made the wise assertion that cutting the trash pile off at its source (drains, business waste overflows, garbage dumps, discarded material from boats etc.) was the only way to significantly reduce the Patch in the long-term.

In the way that more scientists are presenting sensible future-focused approaches to managing climate change (see original papers, later reviewed on f1000 Biology, from Lawler and Tear et al. for a solid review and another from Graham and McClanahan et al. on coral reef ecosystem stability), so Project Kaisei and other organisations are working on strategic responses to the issue, such as recycling retrieved waste and using large nets to snare bigger pieces of trash and leave marine creatures unharmed.

So arguing with an ocean scientist isn’t a good idea and hopefully government decision makers can come to that same conclusion.

Worthless lie

I’m on record as defending PR in the scientific sphere (and featured in Nature’s From the Blogosphere, so it must have touched a nerve somewhere). I maintain that we will continue to require good public relations, perhaps even more so with the looming spectre of swingeing cuts in publicly-funded science. (I’m a little less enamoured of paying PR managers at a research council double the average professorial salary, but that’s a story for another day.)

Although f1000 (obviously) isn’t associated with any particular institution or scientist, we do like to put out the occasional release covering interesting science that’s been picked up by the Faculty. This is an interesting exercise as a lot of newsworthy stories have usually already been released by the journal of the original article, or the author’s home press office, by the time our evaluations come in. But we do find a lot of important (or, let’s be honest, slightly quirky) work that hasn’t got much further than a couple of interested specialists, and we like to bring it to a wider audience. (Sometimes this attracts criticism from talentless hacks, but hey, it’s all good). Besides, if six month-old ‘news’ is good enough for the Beeb, it’s good enough for us.

Anyway, we’ve been reasonably successful in our forays into PR, getting quite a bit of attention from all sorts of places, including the national press. Some of our more popular topics have included cartilage repair, cocaine addiction and seasonal effects on multiple sclerosis (rather than deluge you with links, all our releases are archived at EurekAlert.) SP has made a glossy brochure of media coverage, which you can have a look at if ever you care to visit me in the shadow of the BT Tower.

Interestingly, the Royal Society of Chemistry has also been experimenting with PR. Brian Emsley recounts how ‘light’ news stories—such as the importance of adding soy sauce to your gravy— raise the profile of an organization (in this case the RSC), and basically prepare the ground for the ‘serious’ stuff. Like ground bait, or artillery barrages to soften the enemy before sending in the infantry. We’re trying to do a similar thing to the RSC; raising our own profile and that of science more generally. It’s all part of the science communication bug I have, and a way of getting people in general more ‘comfortable’ with the scientific process in general (as well as getting our content out to professionals—practice nurses perhaps—who might not have seen it).

So, we’re still experimenting, and we’ll probably get some things wrong, and hopefully we’ll get other things right, but I’d really like to know what you think about PR and the direction we should be taking it.

Come Home

Back when I was an acolyte in the service of science, I worked on an interesting little big protein by the name of talin. This 270 kDa sucker is involved in focal adhesions: the ‘ankle’ of the cell, joining the actin cytoskeleton to the outside world. Focal adhesions are fascinating and complex, and if I had access to my thesis right now I’d draw you a picture. You’ll just have to take my word for it.

Talin is a molecule that back then was probably too big a problem for a grad student to tackle more or less single-handedly; the post-doc was was concentrating on some genetic analysis and my supervisor was taken up with the department’s computing services, which left very little lab time. I did manage to show that talin didn’t, as had been proposed, cap or nucleate actin polymerization (a negative result that was essentially unpublishable), and I also developed a long-term love of immunofluorescence microscopy. It appears we were ahead of our time: talin is closely involved with integrins (which see) and seems to be enjoying a (re-)surgence of interest lately.

Back to focal adhesions. Formation of these structures, completely essential to cell adhesion and migration, has been pretty thoroughly prodded. What’s interesting is how focal adhesions disassemble, so that the moving cell doesn’t get stuck. Again, this is something I had a professional interest in: one of my projects in Cambridge involved  the determination of how moving cells generate the required motile force, or how they put their ‘feet’ forward’. We used a model system and discovered that essentially it’s gel effects. You take a load of little rods (= actin filaments), grow them, and the space they fill is disproportionately large, driving protrusion. What we didn’t do was look at the trailing edge of the cell, how the ‘foot’ comes up again. That was something I would have dearly loved to work on, and if I’d stayed in Cambridge, or even in science, I might have worked on it.

Clathrin

Good job I didn’t, because we’ve just published an evaluation of a paper showing that focal adhesion disassembly is just as complex as assembly. It turns out that our old friend clathrin, along with two of its adaptors, gets directed to focal adhesions by microtubules, and, as you might expect seeing as clathrin is involved, the integrins are reincorporated into the cell by endocytosis, and recycled (rather than being left behind as the cell walks away. I don’t think any of us thought much of that hypothesis anyway, but I mention it for completeness.)

The researchers used total internal reflection fluorescence and watched individual molecules on the underside of migrating cells scooting around. The clathrin sidled up to focal adhesions, hooked up with integrin; and the two left the party together.

Get your coat, you’ve pulled

Just as we don’t think that our spaghetti/copper wire/gel effects produce all the force required for forward motion, neither is it certain that all focal adhesion disassembly is driven this way (the paper says that depleting clathrin reduces disassembly by 60-80%) . Talin itself has a head domain and an extended domain, and there is a calpain protease recognition site at the join (this was an immense pain when purifying the native protein; I had to make sure everything was swimming in protease inhibitors). Similarly, it’s possible that calpain actively degrades one or more focal adhesion components to make sure the whole thing gets packed away nicely, even if that does seem expensive in energy terms.

It doesn’t stop there, of course. Somehow these integrins have to get recycled to the front of the cell. It would makes sense for the little blighters to make their way through known endocytotic pathways and be ready for reassembly into focal adhesions at the business end of the cell, this hasn’t yet been demonstrated directly. It’s probably a mass effect. He said, airily.

Private investigations

One of the really great things about science is its potential for self-correction. If you have an hypothesis, a result (strange or otherwise), a set of data, it can be tested by anyone. This is encouraged, in fact: when you publish you’re not just saying ‘look how clever I am’ but also ‘here’s something new! Can you do it too?’. This philosophy is diametrically opposed to that behind Creationism, say; or homeopathy. In those belief systems whatever the High Priest says is of necessity true, and experiment must bend around them until the results fit.

This means that, in science, a finding or publication that people get very excited about at the time can be shown to be wrong—either through deliberate fraud, experimental sloppiness (although the boundary between the two can be fuzzy) or simply because we’re as scientists wiser now than we were then. This happens, and it’s normal and part of the process. We should welcome it; indeed, my friend Henry Gee has claimed that everything Nature publishes is wrong, or at least provisional.

So what we have to do is be completely open about this, no matter how embarrassing it is for the journal that published the work in the first place.

You know where I’m going with this, don’t you?

It was Derek Lowe who first alerted me to a paper published in Science last year, with the ome-heavy title Reactome Array: Forging a Link Between Metabolome and Genome. This was flagged as a ‘Must Read‘ (free link) back in November, because according to our reviewer Ben Davis

If this worked it could be marvellous, superb.

However, as Ben said in his evaluation,

this work should be read with some caveats. Try as we might, my group, as well as many colleagues, and I have tried to determine the chemistry described […] In my opinion, this is a work that deserves a “Must Read” rating and I strongly encourage the reader to read the source material and reach their own conclusions.

And as Derek points out, Science published an ‘Editorial expression of concern‘, noting a request for  evaluation of the original data and records by officials at the authors’ institutions, as well as mentioning it on their blog. Heavy. Immediately I saw this, I let our Editorial team know we might have a problem and we published a note to warn our readers that the work described in the paper was suspect.

Today we published a dissent to the evaluation from Michael Gelb, who says

There are many reactions shown that seem unusual and controversial […] My colleagues and I have tried to decipher the chemistry shown in Figure 1 of the main text and in the supplemental material. Many of the indicated reactions seem highly unlikely to occur, and the NMR data showing that some of the structures that were made are confusing and controversial.

We’ve also published a follow-up from Ben:

I agree wholeheartedly with the sentiments expressed in the Dissenting Opinion. The chemistry presented in this paper and in the online SI has varied in its description and content worryingly over the last 2 months.

and, rather tellingly,

as yet no chemical samples or key reagents have yet been made generally available.

(One of the usual conditions of publishing in reputable journals is that you make reagents available to other scientists, so that they can repeat your work. Failing to honour this commitment is not playing to the rules.)

It’ll be interesting to see when, not if, the original paper is retracted; and by whom.

And this, people, is the self-correcting wonder of science. Remember this, next time someone starts rabbiting about scientific conspiracies, or sends you their new theory of general relativity, or anything else that sounds crazy. It probably is.

Here we go again

CAM is a group of diverse medical and health care systems, practices, and products that are not generally considered to be part of conventional medicine. While scientific evidence exists regarding some CAM therapies, for most there are key questions that are yet to be answered through well-designed scientific studies—questions such as whether these therapies are safe and whether they work for the purposes for which they are used.

So says the US National Institutes of Health about ‘complementary and alternative’ medicine. What the NIH doesn’t tell you is that some people get quite ratty, and indeed irrational, when talking about it. It also fails to point out that that if something doesn’t work it can hardly be called ‘medicine’, so the phrase ‘complementary and alternative medicine’ is a bit pointless.

Yes, I know: CAM means anything that isn’t ‘Western’ medicine, the stuff that often has huge amounts of evidence behind it and that actually makes people better. Or maybe anything that isn’t pouring money into the coffers of multinational pharmaceutical companies—as if that’s somehow worse than pouring money into the coffers of those who offer sugar pills and countless different vitamin formulations.

Anyway, the point is that anything that claims to be a medicine can be tested, to see if it actually does make people better. Isn’t that what we’re trying to do? Anyone who tells you that a CAM therapy can’t be tested is lying to you, and by the way, when did you last see your wallet? The endpoint for all medicines or treatments is really quite simple: does someone who is unwell get better as a result? Where things get complicated is in the testing protocols you use: in defining ‘better’; in the appropriate choice of controls; in statistical analysis; in dosage; and indeed in defining what ‘unwell’ means in each case. (It’s trivial to feel a bit run down, take some supplement or do yoga and feel better again, and say that the intervention worked; when in fact you had just had a couple of bad nights’ sleep. This is why the plural of ‘anecdote’ isn’t ‘data’.)

More problems arise when people start getting lazy and lumping together things like herbalism and acupuncture with homeopathy. One of those involves chemicals extracted from plants, one involves a surgical procedure; and one nothing at all. It makes no sense at all to compare them as equals. (Now you might say that homeopaths treat the patient and not the condition, and you might well be right; but conventional medicine also has that. It’s called ‘bedside manner’ and it’s very powerful.) Now, I have no particular beef with homeopathy per se: if educated, well-informed people want to try it, then that’s their lookout. But when people in positions of authority or responsibility actively deny access to ‘conventional’ medicines that actually work, in favour of witchcraft, I get a bit tetchy.

We talked a week or two ago about a study that looked at a herbal remedy; chamomile. There, chamomile came out as beneficial in cases of mild anxiety. This was a nicely done trial, with a result that wasn’t really surprising. After all, people have been using it for ages (and noticed an effect; presumably if they hadn’t they’d stop buying it) and there’s actually some chemical in it that has a chance of being biologically active. Chamomile tea might well be classified as a CAM, and it works. We can call it ‘medicine’, therefore, even if it’s not prescribed or ‘conventional’.

A study reviewed on f1000 this week examined acupuncture in the management of post-operative pain in children. Again, actually doing something to people had an effect; and this is with anaesthetized patients (so you might think that patient bias is reduced). This reminds me, parenthetically, of my favourite placebo story. Back in the Fifties a particular treatment for angina involved ligating certain arteries. When people did the proper experiment, they found that a sham procedure (under sedation, not anaesthetic) was just as effective, at least in the short term. Rather than say “hey, we’ve discovered something odd here” the surgeons stopped doing the procedure (that’s because they were medics, I presume. Were they scientists they might have played with the observation a bit). This also is not too surprising: acupuncture seems to work. We might not know how it does, but at least we can guess that the mechanism involves stimulation of certain nerves or release of endorphins, or something testable (but probably not some mysterious ‘life energy’):

For short-term outcomes, acupuncture showed significant superiority over sham for back pain, knee pain, and headache. For longer-term outcomes (6 to12 months), acupuncture was significantly more effective for knee pain and tension-type headache but inconsistent for back pain (one positive and one inconclusive).

…

The accumulating evidence from recent reviews suggests that acupuncture is more than a placebo for commonly occurring chronic pain conditions. If this conclusion is correct, then we ask the question: is it now time to shift research priorities away from asking placebo-related questions and shift toward asking more practical questions about whether the overall benefit is clinically meaningful and cost-effective?

And then we have the homeopaths. Bless them: although they say we can’t, or shouldn’t, test homeopathic ‘treatments’ like we test other CAM, sometimes they’ll go ahead anyway. And they’ll say things like

Piglets of the homeopathic treated group had significantly less E. coli diarrhoea than piglets in the placebo group (P < .0001).

Which, if true, would be brilliant.

But it’s not, is it? This is why they’re publishing in Homeopathy and not somewhere like Nature (because believe me, if it were true this would be Big News). Even so, that’s a remarkable claim, and I had a look at the paper to see what was going on.

It’s really rather simple. They treated (observer-blind, apparently. I guess the pigs didn’t know what they were getting) sows with either an homeopathic preparation or a placebo (or maybe vice versa. Hard to say). And then they scored the offspring of these sows for E. coli-caused diarrhoea. The piglets that had diarrhoea that wasn’t caused by E. coli didn’t get counted. Funnily enough, those pigs were all in the treatment group, which is how the authors managed to get a sixfold decrease and that rather splendid-looking p value. And how did they determine that those pigs weren’t suffering from that particular form of the squits? Well, it wasn’t by microbiology:

Faeces were cultured to identify enteropathogenic E. coli, E. coli K99 and Salmonella. None of these were identified as present in the faeces sample. This does not per se demonstrate that enteropathogenic E. coli were not present at the farm at that moment. It was a relatively small sample size of three litters, which would not necessarily include the infective agent. Because treatment with Coli 30C had worked before, and E. coli diarrhoea generally can be distinguished based on day of appearance and colour, this was not further investigated.

Translation: “We believed there was E. coli in these pigs. We failed to prove it, but that doesn’t matter because we are strong in the Force, and you should believe it too. And there was no way we were going to check the whole batch, because then we might find an inconvenient absence of what we want to prove.”

And seeing as they didn’t publish the raw data, who are we to argue anyway?

It’s hardly any wonder, with work of this ‘quality’ finding its way into the literature, that homeopaths are still making a fast buck through the gullibility of ordinary people. So I heartily commend to you the 10²³ ‘Overdose’ event on Saturday 30^th January. This is where a bunch of community-minded people are going to, en masse, swallow a whole bottle of some homeopathic pills to proof they’re ineffective. And to reward you, loyal reader, for making all this way to the end, here’s a joke:

Did you hear about the homeopathy patient who died of an overdose?

He forgot to take his medicine.