Embryos and Parliament - Part Three (last one, I promise... well, maybe not...)

Turns out that not all MPs turned out to vote on this new Embryology Bill, as flagged up by benb on the badscience forum. Inspired by benb's letter to Chris Grayling, here's a letter I will post in the morning to my local MP, one Eleanor Laing MP.

Dear Ms. Laing,

I am writing to you as a constituent, in reference to the 2^nd reading of the Human Fertilisation and Embryology Bill [HL] 2007-08. According to www.publicwhip.org you were absent from yesterday’s debate, and were not amongst those who voted. I expect there may be mitigating circumstances, and so am taking this opportunity to enquire about your absence from this otherwise well attended and undoubtedly important occasion

I am particularly interested in your stance on the issues raised by this Bill, which represents a landmark in government legislation concerning the regulation of scientific advances. As a post-doctoral research scientist developing novel therapies for debilitating disease, it is heartening to see that the Bill, which proposes to permit the regulated use of human embryonic tissue for life-threatening disorders, has been passed onto the next stage on the way to becoming law.

Indeed, just as encouraging was the well-attended and well-reported rally of scientists, MPs and patient support groups organised by Dr. Evan Harris, Member for Oxford West and Abingdon, which took place before the 2^nd reading (in case you were unaware of this public show of support, I am confident that Dr. Harris will be happy to share the details with you). When issues concerning abortion, the use of embryonic tissue in research and related areas are raised in Parliament, or otherwise find themselves in the public arena, so-called ‘pro-life’ campaigners make themselves heard with vocal and often emotive statements that effectively influence both public opinion and MPs’ voting habits. Such campaigners consist largely of religious groups who base their stance on their ecumenical opinions. Yesterday’s gathering showed that scientists and clinicians, basing their stance on evidence gathered from published scientific data, are themselves ‘pro-life,’ insofar as they are keen to develop treatments that could improve or save the lives of thousands of people with life-threatening diseases such as Parkinson’s and Motor Neurone Disease.

The debate over the ethics of the proposed measures was keenly contested (I and many others attended part of the session in the public gallery as guests of Dr. Harris), and largely consisted of arguments in favour lead by those willing to back scientific advances in a regulated environment, and arguments against lead (in the main) by those wary of offending religious sensibilities and largely outdated definitions of what constitutes life.

In many ways the Bill represents a choice for how we envisage our country being run. Do we wish to see decisions being made on the basis of peer-reviewed, scrutinised, scientific evidence, or would we prefer private opinion and emotive arguments to prevail when drafting such important legislation? As a scientist who supports the Bill, albeit with certain caveats, I would greatly appreciate knowing your stance on the above issues, and indeed would like to know how you would have voted had you attended the debate.

I look forward to hearing your reply, and very much appreciate your time,

Yours Sincerely,

Let me know what you think, and whether you've sent similar letters

Embryos and Parliament - Part Two

So as my last blog entry suggests (blimey, six months without a peep and then two posts in two days - I'd say something about London buses but with BoJo in da house I'd only end up a seething wreck hurling my keyboard at the screen...), I went to the pro-science rally in support of the Human Fertilisation and Embryology Bill. Here's why I think my experiences deserve a whole second entry!


Whilst the likes of Dr. Evan Harris MP and Dr. Ian Gibson MP were fulfilling their media obligations, I was approached by a young lady who introduced herself as a lawyer interested in the Bill. She offered me a leaflet, which I've scanned and reproduced in all its glory above. It appears as thought religionists had infiltrated the ranks of the Geek! We had an interesting discussion, and to be fair to the young lady she was calm, well-spoken, apparently open to a scientific approach... oh, and wrong.

Her objections to the Bill were many. Firstly,n she said, just because scientists can do something, doens't mean they should. Correct in many ways, and a sentiment echoed in the House of Commons chamber, in those exact words, by Andrew Lansley MP as he spoke to table amendments. Fair enough, I retorted, but that's simply a statement, and in itself is not a reason not to progress with scientific advances - of course if there are sufficient reasons not to proceed, be they ethical, moral or otherwise, then so be it, I said. Aaah, said our friend, but just because they can doesn't mean they should... Hmmm...

Then, what amounted to a straw man was waved in front of me. Ten years, she said, ten years people have worked with embryonic stem cells, and not one treatment has come about yet! Why should we support such an inefficient avenue of research when it's such an ethical minefield...! Now, if you'd read my recent post on what I do for a living, you'll recall that I'm involved in gene therapy. In drug development, ten years is not, repeat not, a long time - in fact, for a biological therapy, it would be a short time... Just goes to show how heightened expectations can lead to misconceptions and gross distortions - just because it's taken ten years so far, doesn't mean the route to discovering new stem cell-based therapies is fatuous!

Her next argument saddened me. Amongst the scientists, MPs and media folk present at yesterday's rally, were members of patient support groups representing societies and charities for diverse life-threatening and debilitating diseases such as Parkinson's and Motor Neurone Disease - indeed, several patients attended. Knowing this, our Christian Lawyer (for by know it had become apparent that she objected to embryonic stem cell research and abortion largely on religious grounds - shock...!) actually said the following:

But should science proceed at all costs? Should we pursue stem cell research at all costs?

As I looked at her quizzically, she continued,

I mean, what about the cost to human dignity...?

Human dignity...?! I almost choked. Here we were, able-bodied and sound of mind, in the presence of people with devastating neurodegenerative disease who were wheelchair-bound, losing control over bodily functions and gradually becoming vegetative, here we are with our faculties intact, and we pontificate over how using embryonic stem cells would diminish human dignity...?!! God, I thought, give me strength... oh, wait...

Then it struck me. Science and medicine want to research all possible avenues to help understand and treat conditions that strike at the heart of what it is to be human. Whilst those opposed to such research use their supposition of what it is to be human to deny these same people the chance to have their lives improved, all because of what was written thousands of years ago in a book (or books) they have chosen to believe in.

In the end it was (somewhat oddly) a Conservative MP, our friend Mr. Lansley, who put it succinctly - and, courtesy of Hansard, I quote:

Although research on reprogramming adult stem cells is encouraging, it would be foolhardy to block embryonic stem cell research and ... We should be careful not to preclude different models of research that have the potential to deliver effective therapies for life-threatening diseases.

In other words, whilst pursuing other sources of therapeutic cells, we must not prevent research into embryonic stem cells as they are potentially beneficial. Succinct, true, and well said. Well done that man, if only others agreed...

Embryos and Parliament - Part One

My thanks first and foremost to Ben Goldacre for advertising the second reading of the Human Fertilisation and Embryology Bill in the House of Commons. And more importantly, my thanks to Evan Harris MP and his team for organising a demonstration of support on the lawns across from Parliament House, which I attended today.

See, Parliament was today debating whether to pass this important Bill, and Dr. Harris rightly thought it was about time the scientific and medical community voiced its support for the research that would be permitted by said legislation, in a regulated and tightly controlled framework, using human embryonic stem cells and so-called 'human-animal hybrid embryos.' The afternoon began with a gathering at Old Palace Yard of scientists, clinicians, charities representing patients with debilitating and fatal conditions such as Parkinson's disease, and Members of Parliament. In keeping with organisations such as Pro-Test, this group aimed to show MPs and the press that it isn't just pro-life Christian groups that can voice their position on the issues raised by the Bill.

I won't go into the details of what the Bill itself entails - that you can read about in excellent detail here or here. The point of this blog post is rather to applaud the efforts of the 'pro-science lobby' that turned up to support a vote in favour of extending the repertoire of scientific research over precluding avenues of investigation purely on the basis of minority objections.

Whether the small gathering (I guess there were around fifty people present) will influence the vote, or the shape the final legislation takes, is hard to tell. But let that take nothing away from the message the demonstration was intended to give: based on current scientific understanding, human embryonic stem cells provide a good potential source of therapies and model systems for testing novel therapies, and so this new framework is required and supported by the scientific community as 'necessary, ethical and right' to quote Dr. Harris.

As the gathering moved out of the sun and into the House of Commons, I was amongst the lucky few that watched the beginning of the debate surrounding the Bill. Alan Johnson MP eloquently moved for the Bill, and during his speech interesting interjections from various Members showed the current debate for what it is. We heard MPs from either side speak in favour of supporting science, whilst some raised objections - the difference was that those in favour cited peer-reviewed, scientific studies to support their argument, those against were only able to prop themselves up on a queasiness expressed by religious groups, pro-lifers and their supporters. What today's debate boiled down to was, quite simply, whether we want to live in a country where evidence-based policy permits tightly regulated and ethically sound research into treatments for life-threatening disease, or in a country which falls foul of the vocal and at times intimidating minority that would prefer to see potential advances in medical science fade as long as their religious sensibilities are not disturbed.

I'll share my other experiences of the day when time permits - for now, suffice to say that as science progresses, as our country forms the vanguard of world-class biomedical research, us scientists ought to be prepared to come out of the woodwork more often to support the Parliamentary ratification of our evidence-based approach to health and disease.

A double-blind approach to restoring vision

After a much regretted hiatus, I was driven to write this blog post by the frankly extraordinary experiences I’ve had in recent weeks regarding ‘alternative’ therapies for disorders that cause blindness. Apologies for the long post that follows - if you follow it all the way to the end I promise it'll be worth it...

Firstly, a disclaimer: I am a molecular biologist, working on gene therapy for retinal disorders. You may be familiar with our work via the recent media interest surrounding the publication of results from our Phase I/II clinical trial for gene therapy for a form of early-onset sever retinal degeneration called LCA (I don't think the full article is behind a paywall so you should be able to access it, any probs please le me know!). Indeed I'm writing this from the USA where our research group has just presented the findings to a major conference.

I say this not to gloat about how fantastic our work is (although of course it is...), but rather to make a point. That is, there are many academic research groups working on several well-researched treatment options for the several forms of retinal disease that lead to blindness - indeed a group in the USA published the results from their trial at the same time as us. These potential therapies are based on research into how the various diseases are inherited, how mutated genes can be replaced or modified, and how such potential therapies can be translated from cells to animals to people. This is, after all, how science works - progress through peer-reviewed publication and controlled studies that lead to careful use in clinical trials.

Of course patients with retinal degeneration don't really care about how a treatment for their condition is developed, as long as it restores vision. But that makes it all the more important to ensure that developments such as the trials I just described are handled well by the media, that people understand how we've arrived at the stage of restoring vision to people losing their sight, how we may proceed to widen this type of therapy to other conditions. So, this is where the fun begins.

Last week I went to Madrid, to speak at a meeting organised by the Spanish Retina Foundation. They had one day of talks for a clinical and scientific audience, and one day of talks by the same speakers, to patients, relatives and carers of those with retinal degeneration (it was truly a novel experience to attend a conference in Spain without knowing a word of Spanish, although the United Nations-style live translation of lectures was amazing). I spoke on both days, describing our group's work on gene and cell therapy for blindness, describing the ins and outs of the work leading up to the trial. The patient audience was really engaged in the talk, and took a great deal of interest in our work - of course they did, they're hoping that such treatments may one day help them or their children see.

I shared the stage with a Spanish scientist who told the audience about other therapies for retinal disease, describing amongst other things some work published last year where specific anti-oxidant compounds were given to mice that suffered retinal degeneration, and there was some protective effect. This is one study, in mice, and although it's quite robust, needs repeating and refining before we tell LCA patients to rush out to Holland and Barrett to stock up on vitamin pills. But at least one member of the audience seemed to understand it as "oral anti-oxidants improve sight," because at the end of my talk he asked the following question:

As you mentioned, alternative therapies such as vitamins may improve sight. What role do you think Ayurvedic Medicine may have to play in retinal degeneration?

?!

I took a deep breath before answering - here I was representing my lab, in front of hundreds of people, and the last thing I wanted to do was lose it. My answer consisted of phrases like "we believe that therapies for such severe diseases need to be properly researched" and "should there be any evidence for efficacy of a treatment, then and only then can in be recommended" and "as the whole point of this conference was to inform you of the scientific process involved in gathering evidence for a therapy based on genetic research, I would advise that any therapies without a basis in evidence are not pursued." How else to deal with such an enquiry? Of course I don't want to be dismissive of the situation my audience was in - any therapy, any treatment, anything at all that could work would be so useful, but the use of "alternative therapies" to treat disorders in which cells in the retina die is, err, somewhat misguided. I emphasise here that I hold nothing against the chap that asked the question - being blind is unimaginable for those of use fortunate enough to read these words, and if someone tells you that X, Y or Z might work, you'd trust them. But how did we get to the stage where such "alternative" approaches are seen as being just as valid as the scientific approaches...?!

Turns out that he wasn't alone in wanting to apply woo-woo for blindness. As someone with a PhD in gene therapy for retinal degeneration, websites like this one peddling a compound called Tostitin make me cry. Classic woo tactics are used - testimonials asserting that the stuff works, guarantees of safety and efficacy, and of course a link to a site where you can pay for this compound by credit card.

The amazing 100% guaranteed treatment for Retinitis Pigmentosa that is bound to leave you amazed!

No matter how long you have suffered from Retinitis Pigmentosa we assure you that with use of Tostitin you will regain your condition faster than any other solution currently available.

Tostitin is an established treatment and produces time tested results.

Tostitin's composition is 100% safe and all its ingredients are purely natural and free from any side effects.

Not only is this dangerous, in that patients surfing t'internet could well believe that there are homoeopathic remedies for their conditions, but it totally undermines the entire research effort into remedies and treatments that are legitimate, safe, and could actually work.

Together with the Ayurvedic question from Madrid, this last week has been a strange one - on the one had, members of the research team I'm part of have been heaped with praise for their diligent, well-controlled, scientifically sound, superbly presented and ultimately successful clinical trial of gene therapy in the eye. And on the other, we have a public willing to ignore all this and jump into the unknown using so-called alternative therapies.

Sometimes I just despair...

Money for an old helix?

Where there's money to be made, you can bet your bottom dollar that in an unregulated market people will exploit ignorance, peddle half-truths and spin-doctor evidence in order to sell their "miracle pills" or some such.

And there's definitely gold in them thar genes. According to this article in the New Scientist (the full article is behind a paywall, sorry...) there is great concern about over-the-counter genetic tests which claim to find out whether you are at risk of killer diseases such as heart disease and cancer. Concern based on the fact that by reducing complex conditions which have several associated risk factors down to a black-and-white test (which costs hundreds of pounds), the public is being duped into a false sense of heightened expectation from medicine and science.

There are thousands of scientific studies dedicated to unearthing genetic variants which increase the risk of contracting serious illnesses (just put the words "gene variant disease" into the PubMed search engine and see for yourself). The majority of these controlled, well executed, peer-reviewed studies are of course invaluable, but it's how companies and individuals exploit the findings which is of concern.

The recent explosion in genetic data has lead to myriad gene variants - often single base differences between your gene that encodes protein X and my sequence - being linked with increased susceptibility to disease Y. Note my use of language here - we're talking about how having a particular variant of gene X makes it n% more likely that you will develop disease Y. This is not, repeat, not, the same as discovering the gene defect that causes an inherited condition. In the popular press, however, this process gets boiled down to "bad version of gene X causes heart disease/diabetes/hair loss/etc." In other words, people are often lead to believe that if there was a way of finding out which version of gene X you had, you could put yourself of high alert of developing Y, perhaps even alter your diet or take a prophylactic drug to avoid the fate seemingly hard-wired into you DNA.

This of course is the ultimate dream in "personalised medicine" - screen people for particular gene variants, tell them to eat less fat, smoke less, or even better, take a pill, and they'll avoid ill health. Not as simple as that, I'm afraid.

New tests recently available over the counter are developed based on peer-reviewed published studies which link a particular gene variant - allele - to a given disease. But let's say such a test looks for whether you have the "bad version" of ApoE4, a gene linked with overproduction of cholesterol. Everyone knows cholesterol leads to heart disease, so if I have myself tested for the bad ApoE4 variant I can prepare for the worst, right? Nope, because the jury's still out on whether this biochemical variation in cholesterol production causes an overall increase in the clinical incidence of heart disease. Think about it - just because a version of the gene X causes me to make lots of cholesterol, doesn't mean I'll necessarily develop heart disease, as there are dozens of steps in between. Mere details don't stop companies such as Genetic Health UK from selling an £825 kit that tests for "bad versions" of ApoE4. What do you do with the information once you've tested positive for the bad variant? eat more sensibly? exercise more? drink less? guess what, save yourself eight hundred quid and do those things anyway, 'cos according to most studies knowing which variant of one gene you carry isn't nearly as important as these lifestyle factors are in preventing what are essentially diseases of affluence.

Much worse still may be the cynical "double play" some companies offer, whereby they test your DNA for particular variants associated with elevated risk of disease Y, and then offer ludicrously over-priced combinations of nutrients, vitamins, minerals and the like to counter the effect of said "bad gene." According to Bijal Trivedi's account of such practices in the New Scientist (again, article behind a paywall I'm afraid...),

An investigation conducted by the US Government Accountability Office in July
suggested that the type of nutrigenetic testing offered by four companies -
Sciona, Genelex, Market America and Suracell - "misled consumers by making
predictions that are medically unproven and so ambiguous that they do not
provide meaningful information". The GAO report also criticised some companies
for selling supplements supposedly tailored to a customer's genetic needs. These
"nutraceuticals" cost anywhere from $1200 to $1800 per year, yet according to
the report they differed little from multivitamins available at the local
pharmacy

Cynical, exploitative, extortionate.

As a scientist, you are trained to interpret data in a particular context. In the case of genetic studies looking at which gene variants are associated with disease - so called "linkage studies" - we interpret the occurrence of variants of gene X in terms of odds ratios. This means that if you think about such studies, you're able to judge that whilst having a given genetic variant may increase your odds of developing (e.g.) lung cancer by two-fold, you can't carry on smoking 40-a-day and blame your genes, as the smoking increases your chances of lung cancer by (e.g.) ten-fold. The public at large, however, are taught by a reductionist press and clever marketing that "variant of X causes disease Y," and moreover that taking $2000-worth of pills can counter that effect.

Is this symptomatic of a black-and-white view of science and medicine, where the public expect easy answers to complex, multi-faceted conditions in the form of pills off the shelf? Maybe. One thing's for sure - until over-the-counter tests for genetic variants are subjected to regulation by an independent authority like the MHRA, people will continue to believe that a drop of blood and a simple test can reveal the deadly future awaiting them.

Truly a 21st century crystal ball.

Ig Nobel Prizes - such fun!

Oh how I love this time of year. The leaves are yellowing, the mornings are crisp and clear, but above all, it's silly season.

That's right, it's the time of year when strange, bewildering, baffling science gets acknowledged, nay, celebrated, with the handing out of the 'prestigious' Ig Noble Prizes.

For the uninitiated - the Ig Nobels are handed out every year by folks at Harvard University - well, the awards ceremony is held there at any rate, the prizes themselves are granted by the humorous bunch who publish the Annals of Improbable Research. A parody of the Nobel Prize, an Ig Nobel is given in categories that mirror the actual Nobels, plus a few more thrown in for fun.

As ever, this year the winners' list makes good reading. As reported in the Guardian, the Ig for Medicine was awarded jointly to Brian Witcombe and Dan Meyer, for their groundbreaking meta-analysis study (published in the BMJ, although admittedly in the Christmas special edition which is worth reading itself...!) of the dangers of sword swallowing. The thing with the Ig Nobels is that some of the work is deliberately toungue-in-cheek, almost as if it was carried out with an Ig in mind (a bit like those contrived Oscar-driven movies that seem to have been shot with the sole purpose of picking up an Academy Award), much like the work of Mayu Yamamoto, winner of the Ig for Chemistry. He has developed a method for extracting vanilla flavour, for use in food, from cow dung. Mmmm, nice.

Or how about Glenda Browne's Ig-for-literature-winning research into how the word "the" causes problems for people compiling an index? Ever wondered why your rat just doesn't understand you? Try not speaking backwards, and avoiding Japanese - the winners of the linguistics prize figured out that rats cannot understand these complex aspects of language variation.

Much of the work for which these spoofs are handed out is peer-reviewed and published, some in surprisingly prestigious journals - how about Nature, Physical Review Letters and PNAS for a CV? The physics prize went to investigators whose body of work helps us understand why sheets wrinkle.

From the study of how Viagra lessens the impact of jet-lag in hamsters (I kid you not, this is a genuine study published, again, in PNAS), to a proposal for developing a weapon designed to make enemy soldiers sexually attracted to each other (the so-called "Gay Bomb" won The Air Force Wright Laboratory in Ohio the Ig Nobel for Peace), via a census of the bugs, ferns, crustaceans and fungi that inhabit our beds - the Ig Nobels truly do make the autumn chill that much more fun.

Upcoming Lectures

For those of you that are (un)lucky enough to be in and and around central London during the working day, here's news of two excellent lectures that form part of the Lunchtime Lecture series:

Thursday 11 October 2007 A Lousy Tale of the Naked Ape, Professor Robin
Weiss, (UCL Immunology & Molecular Pathology) Although human DNA is
98 per cent similar to that of the chimpanzee, the infections we catch are 80
per cent different. Most are new acquisitions that we have picked up as humans
spread across the world. In fact, pandemic infections like smallpox and
influenza only date from the last 12,000 years or so after we formed settled
farming communities and later developed large colonies known as cities. Does the
history of infectious diseases help to predict future epidemics?

and:

Tuesday 16 October 2007 Science in an Age of Delusions: Some Examples from Scientific Fraud, Quackery, Religion and University Politics Professor David Colquhoun (UCL Pharmacology) We have seen a progressive erosion of the enlightenment values which form the very basis of science. The fashion for delusional thinking is already widespread among the general public and
politicians. It has penetrated even into universities as power inexorably moves
from academics to managers. Francis Wheen has suggested that this step backward
towards the dark ages started to become fashionable in about 1979. The more
interesting question is, when will it end?

Robin Weiss is undoubtedly one of the greatest scientists alive, revered and rewarded for his outstanding contributions to the field of HIV research - in particular his elucidation of how the virus docks with T-cells (white blood cells) of the immune sytem using the CD4 protein, and his subsequent work on AIDS-related malignant disease such as Kaposi's sarcoma. This blogger was fortunate enough to be have lectures from Prof. Weiss as a third year undergrad, believe me it'll be worth coming along to this.

As for Prof. Colquhoun, what can I add to what members of the badscience.net community already know? This Fellow of the Royal Society (no less) is a heroic campaigner against all things woo and all things quacky, as readers of his Improbable Science blog will testify. His lecture promises to be a triumphant call-to-arms for us sceptics in the battle against bad science!!

so come along, although as space is usually criminally limited, come along early!!