Stem cell therapies, visual disorders and dangerous clinical practice

Yesterday I blogged about the story of Izabelle Evans, a girl who received a stem cell transplant to treat septo-optic dysplasia. Following comments on that piece by Prof. Stephen Moss, Prof. David Colquhoun and Suirauqa, I've done a little more digging around the use of stem cells for treating visual and other disorders - here I try to separate the maverick from the marvellous.

As I've mentioned before on this blog, my research centres around inherited visual disorders - I'm interested in the mechanisms that lead from genetic mutations to disease, and in developing gene therapy treatments. I am fortunate enough to work in one of the very best research groups in one of the very best institutions in vision research in the world - fortunate because I can see first hand (if not always produce myself!) scientific research of the highest order.

Much of that research hints at the enormous potential that stem cells hold for the treatment for an assortment of disorders - not least those affecting the nervous system - by replacing cells lost due to disease.

But, to coin a phrase, I think you'll find it's a bit more complicated than that...

Genuine stem cells originate from the inner cell mass of the early blastocyst-stage embryo - that is to say, they are the small group of cells which can give rise to all the different cell types of the body, from stomach and lung cells (derived from the endoderm), to muscle, skin and blood cells (which derive from the mesoderm) and neurones in the brain and eye (originating in the ectoderm). For a more detailed description of stem cells and their properties, I'd recommend the National Institutes of Health resource for stem cell research, brought to you by the folks behind the scientific publications gateway PubMed.

Aside from these 'true' stem cells, many adult tissues contain cells that are partly developed into 'progenitor cells;' these are often referred to as adult stem cells, and can give rise to most if not all cell types of that particular tissue.

A key development in the last few years has been the creation of induced pluripotent stem (iPS) cells - adult cells, usually take from skin, that are reprogrammed in a dish to behave like actual embryonic stem cells that can give rise to any cells type in the body, even whole organisms in the case of mice.

Stem cells display key behaviours that make them of real interest as potential treatments; they can divide indefinitely (at least on paper), giving a potentially endless source of cells from very few original cells; depending on the environment they are placed in, they can differentiate into any cell type you require; and because they mature in the same way as normal human tissue, when transplanted the differentiated mature cells that arise from can form connections with host tissue and restore function to a diseased tissue. At least, this is what the latest peer-reviewed, scientific literature intimates.

So picture a disease such as Parkinson's, where dopamine-secreting cells in the brain's subsantia nigra degenerate; or muscular dystrophy; or any of the myriad inherited retinal degenerations, where mutations in hundreds of different genes lead to the death of the light-sensitive cells of the retina. These are all diseases where cells die for various reasons, and potentially could be replaced either by stem cell transplantation - in the hope that the undifferentiated cells mature by virtue of finding themselves surrounded by mature brain/muscle/eye cells - or by coaxing stem cells to develop into the mature cells in a dish and transplanting those. And my list of diseases is hardly comprehensive - common conditions such as stroke, heart disease and diabetes could all benefit from stem cell-derived technology.

Little wonder then that there is a great drive towards developing stem cell-based therapies. And real progress is being made, at what is a remarkable rate in terms of medical research. Just taking my own field of eye research as an example, it is now possible to take fibroblasts (a general-purpose cell type) from the skin of a mouse, reprogramme it into an iPS cell in a dish by expressing a few key genes, add in a cocktail of factors known to encourage development into many of the cell types found in the eye (see this excellent review from a current and a former colleague for details), and isolate cells from the resultant mix that look remarkably like mature photoreceptors. On the other hand, progenitor cells from a newborn mouse retina can be transplanted into a degenerating recipient retina and restore - to some extent - sensitivity to light - it's nothing like a complete cure as yet, but proof-of-concept studies show that cleverly manipulating both the donor cell and the recipient retina can allow thousands of these stem cells to integrate and form connections with host cells. Combining the two techniques - generating induced pluripotent stem cells and developing them in a dish to resemble adult retinal stem cells for effective transplantation - remains the elusive goal.

Thousands of such studies show that stem cells of all flavours have great potential as treatment - but they also show how difficult they are to work with, how little we understand of how they work, and the dangers they represent.

Which is why careful, rigorous, scientifically robust studies are needed before stem cells are widely applied to patients in the clinic. There are hundreds of official clinical trials using stem cells underway, for many diseases - partly the number is inflated due to a loose definition of stem cells - and these vital studies will provide answers to many important questions over safety and efficacy. Without systematic trials of this nature we really can't say with any confidence that stem cell therapy is safe for humans, let alone effective.

This is what makes the behaviour of certain clinics and doctors, seemingly more so in China than anywhere else, disturbing. As I wrote about yesterday, a Chinese clinic is offering spinal injections of stem cells from the umbilical cord as a treatment for a host of diseases. Commenting on that piece, Prof. Moss said he found nothing on PubMed suggesting the clinic has a publication track record to speak of. Looking for more details, I found this website which is an astonishing mixture of anecdote, patient testimonials and extraordinary claims - and not one mention of a properly conducted, peer-reviewed and published study.

To quote the great Carl Sagan, "extraordinary claims require extraordinary evidence" - and I see lots of the former and virtually none of the latter.

The blogger Suirauqa (whose own latest blog post links to another scientific study  linked to a story on NPR which cast a somewhat skeptical eye on the claims of efficacy for Chinese stem cell treatment in the case of Laylah Teague. The story is still on the credulous side for my liking, but at least discusses the possibility that any treatment effect may be placebo-driven (patients tend to receive massages and other 'alternative' or palliative care alongside their stem cells), and/or short-lived - as well as the spectre of dangerous side-effects.

I despair at this sort of thing - along with the enormous potential as therapies, stem cells carry with them unknown dangers which could easily be fatal. Medicine is not perfect and even the safest looking treatments can turn out to be fatal - let's hope that the irresponsible, cavalier by-passing of the scientific method and lack of respect for due process on display at these clinics doesn't harm the patients desperate enough to pay massive sums demanded.

Stemming the tide of cell therapy stories, or, Where are the Methods and Materials in this journal?

Thanks and hat-tip to the outstanding blogger @gimpyblog, who Tweeted the story in the Sun on which this post is based; thanks also to the brilliant @stephenemoss for encouraging me to write this post; and apologies for the headline...

Time after time bloggers criticise newspapers - mostly but not exclusively the red-top tabloids - for their coverage of science stories. Ranging from the baseless scaremongering around MMR to the PR fluff of wacky equations and bogus (careful...) 'trials' of dietary supplements, the media's inability to report on scientific material accurately or fairly is not news in itself - just take a look over at badscienceblogs.net and you'll see dozens of press articles pwned for indulging in bias, statistical error or just plain idiocy.

To the roll-call of infamy in science journalism we may add stories from earlier in the week (in The Sun and The Mirror amongst others) regarding four-year-old girl Izabelle Evans, some stem cells, and China.

The Sun reported that 

LITTLE Izabelle Evans who was born blind has seen her mum and dad for the first time at the age of FOUR — thanks to a miracle procedure carried out on the other side of the world.

Brave Izabelle can now see up to three feet and recognise her parents' faces following groundbreaking stem cell treatment 

(emphasis original).

Curious, I read on in hope of finding out what cell type was used in the treatment, what the mode of delivery and dosage were, how efficacy was determined - alas, no luck.

Helpfully, The Mirror went into more detail, describing how septo-optic dysplasia caused Izzy's visual impairment:

[Izzy] only has a few hundred optic nerves (sic) sending information to her brain. A person needs millions to be able to see. Her family heard about the stem cell treatment which involves injecting the spinal canal with cells taken from umbilical cords of healthy babies. The cells are then used to rebuild optic nerves.

Leaving aside the technicalities - we only have one optic nerve per eye, made up of the axons of millions of neurones - several questions arise. Was the injection of umbilical stem cells carried out under a clinical trial protocol or offered as a commercial service? What precautions were taken to ensure that Izabelle's immune system did not react adversely to receiving cells from another person - or were Izzy's own cells, perhaps frozen down at birth, used? How was the patient's vision tested before and after treatment?

Of course, had we been reading about Izabelle's case in a peer-reviewed article in a scientific journal, we may well have had the answers. As it is we're left with the tantalising story of a little girl (cue pictures of her with family in front of seasonal decor) and her anecdote of 'improved vision' following 'stem cell therapy.'

Having seen at close quarters how a genuine clinical trial is carried out - with rigorous pre-clinical testing of the treatment lasting years, massive regulatory hurdles to be overcome (rightly) and the thorough post-treatment reporting that is required to qualify for publication in a high-flying journal - I feel the need to express my disappointment. Not only does The Sun put in jeopardy it's otherwise decent record on reporting health issues (not least the waste of money that is NHS-funded homeopathy), stories like Izzy's unjustifiably raise people's expectations of what medical science can deliver.

Another aspect of both the Sun and Mirror's reporting concerned me - the focus on the non-availability of such treatment - whatever it constituted - in the UK, and the fundraising that allowed the Evans family to head to China where she was treated. There may well be good reasons why direct injections of stem cells into the spinal canal are not carried out in the UK - it may be for lack of the very safety and efficacy data missing from Izzy's story. What we don't need is for families of patients with rare disorders - despite being understandably desperate for anything that might help - to jet off to jurisdictions with lax controls over clinical protocols and less regard for patient safety - which may well be the case here.

By reporting an isolated anecdote such as this, without corroborating evidence on safety or efficacy, journalists do science and medicine a huge disservice. There's nothing wrong with reporting genuinely exciting advances in medical science in the lay press - in fact it's a vital part of making scientific progress for the population at large to understand the likes of gene and cell therapy - it's just that this kind of reporting distracts from the real deal - and makes it that much harder for properly conducted trials and their outcomes to get the recognition they deserve.

Extrapolation in extremis, or, How the Daily Mail went all Homer Simpson and claimed that 'purple is a fruit.'

A big thank you to @Evidencematters on Twitter for pointing out this story...

'Remember to eat your purples: Fruit can 'ward off Alzheimer's, heart problems and cancer,' or so the People's Medical Journal (aka the Daily FMail) tells us.

So, I won't bother writing the rest of this post - instead I'll just head off to buy shares in growers of purple fruits...

Oh, wait...

The Mail story is an object lesson in how to take seemingly sound science and extrapolate its findings to the logical (or illogical) extreme; a picture-perfect example of the art of insinuation, conjecture and wishful thinking. Oh, and it's also an addition to the honourable Oncological Ontological Project (the mammoth classification of which has been completed by Paul Battley) whereby, according to Bad Science maestro Ben Goldacre, 

The Daily Mail, as you know, is engaged in a philosophical project of mythic proportions: for many years now it has diligently been sifting through all the inanimate objects in the world, soberly dividing them into the ones which either cause – or cure – cancer

This time, it's purple fruits which may 'cure' cancer, and help 'ward off' diseases such as multiple sclerosis and Parkinson's - and according to Mail reporter Fiona Macrae it's all there in black and white, written by a scientist no less. No ordinary scientist either - Prof, Kell is a prolific scientist interested in the biochemistry of metabolism, and serves as the Chief Executive of the Biotechnology and Biological Sciences Research Council. The article cites a paper by Prof. Kell from the University of Manchester, and says that the polyphenols contained within purple fruits (and green tea, curcumin and chocolate, although sadly not the Mail's favourite anti-cancer compound, red wine) may help

fight the harmful effects of iron, which can damage cells if it makes its way through the digestive system in the wrong form.

We've been here before on this blog, with a Mail story that linked perfumes to male infertility - again based in some way on studies by Professor Richard Sharpe but that bear no resemblance to the science contained therein.

So I did a little digging - I emphasise the little, as it doesn't take too long to dig for the absurdities in Ms. Macrae's article.

Prof. Kell recently published a review article in the journal Archives of Toxicology, to which I assume (given the Mail's insistence on not linking to original sources...) Ms. Macrae's article refers. If you're interested you can read the full article here, or just the abstract via PubMed here.

Prof. Kell draws on extensive evidence (his review is one of the most thorough and heavily-referenced I've ever seen with over 1,700 references...) regarding the role of iron - specifically, iron that is 'poorly liganded' - in the progression of many seemingly disparate diseases. Poorly liganded iron? Qu'est-ce que c'est?

Iron, as Mrs. Teekblog the chemistry teacher had to remind me, is a transition metal that can exist in several valencies - in other words, it can choose to make bonds with any number of ligands (other atoms/ions/molecules) up to six. Iron is said to be fully liganded when it's bound to its full complement of six ligands - according to Prof. Kell's review, iron within cells that is bound to fewer than six ligands can cause the production of highly reactive hydroxyl radicals (free radicals) through the Fenton reaction, which are well known to cause damage to DNA and proteins and play a significant role in cell death during disease.

Prof. Kell goes on to take a 'systems biology' approach to the role of poorly-liganded iron in disease, postulating that the build-up of the incompletely-bound form of iron may be the 'nexus' that links diseases with apparently unrelated causative factors with seemingly disparate outcomes - that poorly-liganded iron and the free radicals it creates may be the gatekeepers channel various insults to cells - whether genetic or environmental - to causing cell death by myriad mechanisms.

As ever, pictures say much more than words ever could, and this elegant diagram may help you in understanding Prof. Kell's view of the importance of iron's valency in disease:



The review article meticulously trawls through data regarding poorly-liganded iron and its potential contribution various disease processes - and yes, at one point Prof. Kell does indeed mention that

the only way to stop the damaging activity of free or partially liganded ‘iron’ is to ensure that all of its six possible liganding sites are satisfied, whether by endogenous chelators or those added from the diet or as pharmaceuticals

Prof. Kell then lists a sizeable chunk of literature that points to the positive effect that many polyphenols (rings of carbon, hydrogen and oxygen of varying properties found in plants) may have on the chelation of iron - largely these studies are in cells in culture or in animal models that recreate aspects of human disease, using purified dosage of the polyphenol under consideration. The theory is that dietary intake of such compounds may boost the body's anti-oxidant capacity, negating the creation of excess free radicals by poorly-liganded iron - but it remains just that, a theory, and there's already evidence that anti-oxidant supplementation is of little or no benefit when taken in the forms cited in the Mail.

At no stage that I could tell does Prof. Kell mention studies looking at the effect that purple fruits, or green tea, or curcumin (all of which do indeed contain polyphenols) have on the pathology of any disease that may have poorly liganded iron as a contributory factor - presumably because no such studies exist.

To go from Prof. Kell's position to the suggestion in the Mail that purple fruit may be protective is, err, somewhat ambitious. What's clear from the studies Prof. Kell reviews is that when iron is poorly liganded it creates high levels of free radicals, which may be a link between lots of different diseases - but that's about it. I'd say that the evidence to date regarding the use of polyphenols as iron chelators suggests it might be worthwhile conducting prospective trials to determine the effect of fruit-derived anti-oxidant on disease progression - but then how's a sub-editor ever going to boil that down to a catchy populist headline?

A letter to my MP Iain Duncan Smith regarding scientific advisers and drugs policy

I have written this letter to Mr. Iain Duncan Smith, my constituency MP and Secretary of State for Work and Pensions, regarding the proposed shake-up of the Advisory Council on the Misuse of Drugs and the relegation of scientific advice in the formulation of drugs policy. I decided to write the letter following the publication of an Early Day Motion tabled by Julian Huppert MP (Lib Dem, Cambridge); should you feel inspired (!) by what you read, please copy/paste the letter, alter as appropriate and send on to your MP using the funny little box below courtesy of MySociety.org as well - I know Mr. Duncan Smith will not sign given that he is a Minister of State, but the more signatories this EDM gets the clearer the message to the Government - it is not acceptable to pursue a drugs policy based on whimsical populism, nor to relegate scientific evidence to the background. If you do send a letter to your MP regarding this issue, please do come back to the comments below and let me know how it goes - you could even link to the text of your letter...

Contact Your Politician

Enter your Postcode below:

Dear Iain Duncan Smith,

I write as a constituent concerned about the Coalition government's plans to downgrade the status of scientific advice when formulating policy on drugs.

The previous government had a strained relationship with the scientific community, exemplified by the summary dismissal of Prof. David Nutt, Chair of the Advisory Council on the Misuse of Drugs (ACMD), for speaking in favour of an evidence-based approach to drugs policy. The advent of the Coalition brought with it renewed hopes for evidence-based policy formulation, not least with respect to drugs where we've seen decades of failed policies based on little more than populism and a desire to appear 'tough on drugs,' policies which ignore the core aim of harm reduction.

Sadly those hopes appear dashed with the news that the Police Reform Bill seeks to amend the 1971 Misuse of Drugs Act (which established the ACMD and its terms of reference) such that the statutory requirement for six scientific experts to be appointed to the Council is to be removed - leaving the Home Secretary to decide its makeup as they see fit.

The Minister for Crime Prevention James Brokenshire MP claims this is necessary " to add greater flexibility to the provision of advice given to government, in order to ensure that we are able to get more effective policies, given the changing nature of the drugs threat" I fear that this is little more than a cover story for the removal of expert scientific advice from the process of formulating drugs policy; and Paul Flynn MP agrees, as his question to Mr. Brokenshire in Parliament clearly demonstrates (http://bit.ly/hnqpKo).

Moreover, the proposed Bill creates new powers for the Home Secretary to impose seemingly arbitrary temporary bans on substances they chose in the absence of evidence that they cause harm; last year saw a fiasco when the Government rushed to ban Mephedrone in a knee-jerk reaction to exaggerated media reports of its lethality, and these new powers make such baseless bans more likely.

I would therefore urge you to signal the government's support for a rational, evidence-based drugs policy with science at its heart - many people are asking their MPs to sign Dr. Julian Huppert MP's Early Day Motion 1148, the text of which is as follows:

That this House expresses its concern that the proposed changes in the Police Reform and Social Responsibility Bill to the membership of the Advisory Council on the Misuse of Drugs remove the requirement to have any members on the Council with specific scientific knowledge; recognises the importance of evidence-based policy making, especially in the area of drugs policy; and requests that the Government brings forward amendments to the Bill to ensure that a reasonable proportion of the members of the Council have relevant scientific experience.

I am aware that Members of the Cabinet do not usually sign EDMs, but would request that you indicate your support regardless by return of post. It is vital that Parliament passes legislation on matters of public interest based on sound scientific evidence, and these measures undermine that goal; I request that you seek a way for the ACMD, and other advisory committees, to retain their integrity and scientific rigour.

I eagerly await your reply - for your information, this letter will be posted on my blog (teekblog.blogspot.com), as will - pending your permission - any reply you send.

Yours sincerely,

Teekblog

Fat Chance - the hidden inequalities in public health

An edited version of this post is cross-posted at The Vibe Online, an excellent political internet magazine. I also have a letter published in The Guardian along the same lines.

The Health Secretary Andrew Lansley MP has been a busy man since taking office. Not content with driving through radical reforms to the NHS – including controversial plans for healthcare budgets to be handed over to consortia of GPS – he recently unveiled the Department of Health’s White Paper on Public Health – Healthy lives, healthy people. Whilst this White paper sets out a compelling case for the need to improve public health outcomes, I want to highlight one policy measure in particular which may well worsen the picture considerably – that of putting major food corporations in charge of setting policy, which the blogger Dr. Aust says is akin to putting the fox in charge of the chicken coop.

The case for improving public health revolves around the recognition of the intolerably large inequalities in mortality and morbidity that exist within the country. By now the statistics are probably familiar to the reader; studies lead by UCL’s Prof. Sir Michael Marmot shows that there are ‘gaps of up to 7 years in life expectancy between the richest and poorest neighbourhoods, and up to 17 years in disability-free life expectancy.’

The previous government did of course have policies in place to tackle poor public health, defended with great vigour by Prof. Joe Millward in The Guardian last week. Of particular concern for Prof Millward is the government’s intention to place major fast-food and beverage corporations at the heart of setting public health policy; he argues that

the increase in childhood obesity has now stopped

and that

[t]his is almost certainly because of a coherent, effective policy on diet, implemented by the Labour government following decades of opposition from the food industry.

As evidence for his former claim (which he repeats later in his article, suggesting that the “prevalence of obesity is falling in girls and no longer increasing in boys”), Prof. Millward cites a study published in the International Journal of Obesity. This study does indeed show that the proportion of children who are overweight and/or obese didn’t increase between 1997 and 2007 and so appears to support Labour’s record on public health – until we look a little closer at the data.

The authors of that study describe a disturbing underlying trend – in scientific terms it’s more than a trend, it’s a significant finding – that seriously undermines Prof. Millward’s championing of the previous government’s success in curbing obesity; moreover it poses serious questions about the current government’s approach as well.

Stamatakis et al. show that the odds ratio (a measure of how likely an outcome is) for children being overweight and/or obese was no greater in 2007 than in 1997 – an apparent vindication of public health policy at the time. But when they separated the subjects they studied not by gender but by socio-economic position – in other words, by income and class – those in the lowest bracket were nearly twice as likely to be overweight and/or obese in 2007 than they were ten years previously, whereas there was no significant difference for children in the highest bracket.

The finding is worth re-stating and emphasising. More deprived children were overweight in 2007 than was the case 10 years before then, whereas children from better off families were no more likely to be of overweight – put bluntly, under the last government poor kids got fatter and rich kids didn’t. Any overall trend towards better weight control in the population at large – which Prof. Millward claims is a result of Labour’s health policy – appears to mask a significant worsening amongst the poorest in society. The deterioration of this marker of public health may well be hidden as widening of inequalities rather than worsening overall trends, but it’s there nonetheless – and it’s vital we don’t miss this point as Prof. Millward seems to have done.

So here’s the crunch. With the poorest already suffering from lack of affordable means for exercise and poorer diets, the authors devastate Labour’s approach to improving public health:

As lower socioeconomic groups tend to be wary of measures and messages aimed at changing their lifestyle because they see them as ‘nanny-statism’ that erodes their autonomy it is possible that policies targeting children's eating and physical activity habits have been perceived less favourably by lower-income and social-class groups.

This is where Mr. Lansley’s White Paper gets things both nearly right – by devolving funding and responsibility for improving public health away from the central State to local authorities and focusing on results not fancy campaigns – and so very wrong – by drafting in the very vested interests that fuel the obesity epidemic to dictate health policy. Because if a policy that purports to tackle inequalities in health recruits as its executive arm the corporate entities responsible for widening the gap between the rich and poor, whose aim is to maximise their profits by selling to people whose health they are now charged with improving, who’s to say that in another 10 years time we won’t be looking back at the co-opting of the junk food industry as the point at which the poor, already getting fatter than the rich, finally saw the government make their health subject to the vagaries of market forces.

Policy-based evidence - Government proposes to remove scientists from drugs advisory committee

Government's relationship with the scientific community has been strained for some time; whether over the provision of empty sugar pills on the NHS, the future of research funding or the proper place of evidence in formulating government policy on drugs.

There is particular concern amongst scientists that scientific evidence is wheeled out in defence of a political viewpoint when it is deemed convenient, and ditched in favour of dogma, expedience and ideology when it isn't. The sacking of Prof. David Nutt as Chair of the Advisory Council on the Misuse of Drugs encapsulated the breakdown of trust between government and the scientific advisers it appoints - and it appears the Coalition government is prepared to travel further down the route of downgrading scientific advice when it comes to formulating drugs policy.

News reaches us via Imran Khan, Director of the Campaign for Science and Engineering (CaSE), and via The Guardian, that buried in the new Police Reform Bill is an amendment to the Misuse of Drugs Act of 1971 - which established the ACMD and its terms of reference - that removes the obligation for the Council's members to be chosen from specified professions.

Furthermore, the Bill as drafted gives the Home Secretary powers to institute temporary bans on substances that he/she feels are worthy of banning - no matter what the scientific evidence may suggest - much like the fiasco over Mephedrone that unfolded nearly a year ago.

Far from placing scientific evidence at the heart of government policy-making, the Coalition appears prepared to discard the experts it has hitherto relied upon - at least rhetorically - for advice on harm reduction with respect to drugs. The implications for other areas of policy in which scientific evidence ought to play a big role - policy on climate change and public health for instance - are disconcerting to say the least; marginalising scientific considerations when forming policy is simply unacceptable.

Whereas previously the government appeared on occasion to set policy according to the whims of tabloid editors and pressure groups in defiance of scientific advice, they will no longer have to - defy the advice, that is. In relegating the status of scientific advice in setting policy, the government will be free from the constraints of evidence and science as it decides what to ban and what to permit.

Before the reader thinks I'm some sort of evidence-fundamentalist, let's get one thing clear. Often the evidence may be politically unpalatable, tough to sell to the electorate and/or counter-intuitive. On occasion, policy has to take into consideration more than 'bald statistics;' there may be economic, ethical or moral considerations to be made when setting policy, which is unavoidably a political (if not necessary a party-political) exercise.

But that doesn't mean that scientific evidence for or against a political position can justifiably be rejected or ignored. It doesn't mean that the Home Secretary should be able to convene a panel of advisers devoid of those who understand harm reduction and best practice. And most of all, it doesn't mean that these proposals are welcome - it falls to those of us who believe in placing evidence and the heart of policy to lobby, cajole and convince Westminster that removing the scientific basis for policy is just not on.

An open letter to Prime Minister David Cameron: #libelreform needed to protect free speech online

Despite significant advances made by the libel reform coalition over the past twelve months, including a commitment to new legislation to reform the illiberal English and Welsh libel laws, it is still vital that all those interested in defending freedom of expression and the uninhibited movement of ideas maintain pressure on the government to deliver.

The latest boost to the momentum behind the libel reform campaign is an open letter, written by Yahoo!, the discussion forum Mumsnet and the Internet Service Providers Association (ISPA), calling on the Prime Minister to urgently reform the unfair libel laws in this country.

The signatories to the letter are particularly concerned by the current 'multiple publications rule,' which holds that an allegedly defamatory statement is considered to be a new libel against a claimant not just upon publication, but every time said statement is downloaded or accessed online - potentially thousands of times a day in the case of high-traffic websites such as Mumsnet.

Justine Roberts, CEO of Mumsnet, also raised the unfair implications the current libel laws have for large websites with many comments posted by third parties, for which hosts are currently responsible and potentially liable; Justine said:

Mumsnet Talk receives around 25,000 new posts each day; it is impossible for us to pre-moderate each one, even if we wished to do so. It is both impractical and unfair that we should be threatened with legal action (and the attendant costs) over individual posts by third parties.

Stating the case for web service providers, Nicholas Lansman, Secretary-General of the Internet Service Providers’ Association (ISPA), said:

ISPs are currently in a position where they may have to decide what bears defamatory meaning, putting the intermediary in a position of judge and jury over content. We therefore support the call for an innocent dissemination defence, that ISPs should only be forced to remove defamatory material that has been decreed defamatory by a court or competent authority, and to bring libel law into the twenty-first century through the creation of a single publication rule.

ISPA's position is particularly delicate given the current government's position towards net neutrality, which is set to allow the creation of a tiered internet service with those willing and able to pay more gaining access to the fastest and selected content - the rest of us presumably having to make to do with a more threadbare worldwide web. In combination with the libel laws' requirement for ISPs to effectively censor potentially defamatory content, the free expression of information and ideas faces a pincer movement - and the open letter to the Prime Minister aims to draw attention to the impact of the latter.

The open letter is published to coincide with the publication of a guide to the libel laws as they stand, written by Sense about Science (pdf), which aims to inform bloggers and online journalists of the options they have if they are threatened with libel litigation. As the potentially disastrous consequences of facing legal action - including financial ruin and suppression of information of vital importance to public well-being - become more widely apparent, the guide sets out how to deal with being sued for libel and is essential reading for those who post online.