Jan 10
Posted by: nicholasswetenham  

Does it matter what swine flu is called?

The 2009 outbreak of non-seasonal influenza, which is classified as  A(H1N1) according to its type of core protein and surface antigens, has popularly been referred to as ’swine flu’ throughout the English-speaking world, and equivalent phrases in other languages – for example la grippe porcine in French.

In some countries, however, governments chose not to refer to the new influenza virus by this name in official publications, presumably because it was felt that the association with pigs was unhelpful to the average person since the transmission is not pig-to-human but human-to-human. In France, bizarrely, it has come to be know as la grippe A for short. To virologists, this merely muddles the issue because most normal seasonal influenza deaths are caused by what they term ‘influenza A’, which in simple terms is a family of flu viruses.

Then, I came across this interview in Le Monde with anthropologist Frédéric Keck of the CNRS, discussing France’s particularly low uptake of swine flu vaccination (<10% of the population). I thought I would summarise it in English for your reading pleasure.

Mr. Keck suggests that in addition to swine flu’s low virulence, a number of local factors explain poor uptake. He mentions ‘playing the precaution card’ which perhaps requires a bit of explanation. In France, health and safety measures and other risk aversion measures are often ascribed to the principe de précaution. This is just a fancy way of saying ‘better safe than sorry’. So perhaps that the public are wary of this overused phrase.

Secondly, he suggests that the act of changing the official name to A(H1N1) made the virus seems less alien and new by removing the reference to its animal origin, more like an ordinary flu virus. At the same time, the national communication campaigns stopped reminding people that it was a new virus about which little was known.

Finally, unlike flu vaccinations in the UK which are co-ordinated through GPs, family doctors in France (who are not as central to healthcare as UK GPs in any case) were not involved in the program.

For interest, let us furhter compare UK and French posters which I cam across this winter:

NHS Swine Flu Poster

Catch it, Bin it, Kill it

Les gestes simples

The UK approach is to have a dedicated telephone line about flu so that other medical enquires are not drowned out. The Catch it-Bin it-Kill it phrase has entered the household in the UK. By comparison, the French poster on the right appears to be a far less effective piece of communication. Small writing and long sentences, for a start. The advice reads “Wash your hand several times a day (with soap or a hydro-alcoholic solution) When you sneeze or cough, cover your hand and nose with your sleeve (or a single use tissue) In case of flu-like symptoms, call your primary care physician (Only call 15 in emergencies)”. The information conveyed covers largely the same topics, but I think here the UK posters (although there’s two of them) put it across far more quickly  and effectively.

Dec 21
Posted by: nicholasswetenham  

Mavericks. People showing great independence of thought*.

Some of the greatest discoveries in science have been made by mavericks. Nonsensical untruths have been promulgated by those very same mavericks. Mavericks stimulate the imagination – they lend themselves naturally as protagonists in a stimulating narrative, generating public interest. Heroes like Galileo and denialists like Duesberg all share one thing in common: going against the grain.

As a layperson in an unfamiliar field, how should a skeptical reader interpret the ideas of these controversial figures? I have been pondering on this problem because I recently attended a lecture by Daniel Everett, perhaps the most controversial linguist in the world. Then I read his book. I even attempted to read some of his original peer-reviewed literature and academic criticism of it, with less success.

My interest in Dr. Everett was originally piqued by this New Yorker article, which I recommend as a good lay summary.

Dr Everett started as a missionary with the Summer Institute of Linguistics, attempting to convert an Amazion tribe called the Pirahã to Christianity by translating the New Testament into their language. After many years, he succeeded in translating one of the gospels, only to find that they weren’t interested. The experience resulted in his loss of faith, and eventually, the breakup of his family. Along the way, however, he became a well-known academic linguist and came to appreciate the culture of the Pirahã people for what it was.

He claims that Pirahã is an exceptional language and culture. The cluster of features he describes certainly seem remarkable to foreign ears: no numbers, no colours, no left/right/up/down, no recursion. The ability to communicate purely through musicality – whistling, humming or yelling, all without consonants (even when used, the consonants vary). Only 12 phonemes (distinct sounds). A cultural constraint against discussing things which one has not observed directly or heard from someone who observed it directly (Dr Everett’s so-called ‘immediacy of experience principle’). Seeing invisible spirits without consuming hallucinogenics.

Dan Everett

Some of the linguistic claims fly in the face of Noam Chomsky’s ideas, particularly the lack of recursion. Dr Chomsky is a linguist and philosopher who founded a school of thought that underlies much of modern theoretical linguistics.

Much of the problem with interpreting Dr Everett’s work as an outsider is that he is perhaps the only linguist who speaks the language with a high degree of fluency (other than his ex-wife Keren Everett). While some of the work that he has done can be repeated independently (for example, on phonology, the study of the sounds of the language), much of the work that he has done is harder for non-speakers to confidently repeat. He responds to his critics, and they might find it hard to then counter-riposte, simply through a lack of data available to them and knack for understanding the language in context.

Whatever one makes of Dr. Everett’s claims, he certainly makes interesting point about the scientific approach in linguistics. There is a surprising dearth of study of some of the most diverse ecosystems of language – in the Amazon, Papua, and Australia (perhaps not coincidentally, also areas of great biodiversity). The least-studied languages are in fact to be found there – and are probably the most interesting. This means that there could be a sampling bias the size of Mount Etna in our present data on languages. It is as if zoologists hoped to study frogs without going to the Amazon, or geneticists ignoring organisms in the sea.

So what was the result of my attempt to understand a controversial expert in a field I have an amateur interest in? Well – I have to admit, I will have to keep to the humble limits of my knowledge and say that I haven’t the faintest idea whether any of Dr Everett’s claims are sensible.
Sources

1. Don’t Sleep, There are Snakes: Life and Language in the Amazonian Jungle. Daniel Everett. Profile Books. ISBN-13: 978-1846680403.

2. The Interpreter – Has a remote Amazonian tribe upended our understanding of language? John Colapinto, New Yorker, April 16 2007.

3. Cultural Constraints on Grammar and Cognition in Pirahã. Everett. Current Anthropology 46(4) August–October 2005

4. Pirahã Exceptionality: a Reassessment. Nevins, Pesestky & Rodrigues. Language 85(2) June 2009. DOI: 10.1353/lan.0.0107

*thought to come from the 19th century Texas Politician Samuel Maverick

Oct 21
Posted by: benvincent  

Today saw the release of the paper published in the New England Journal of Medicine containing the hotly awaited data concerning the HIV vaccine trial that took place in Thailand. There was already some discussion of the initial results, which were reported in September and discussed by Colin, amongst others. As has already been discussed, there is a very cautious consensus due to the statistical analysis of the trial only *just* falling on the side of significant. Also there were the issues that the efficacy (capacity to provoke an effect, in this case protection from HIV infection) was only calculated as 31.2% overall, and the non-intuitive fact that each of the two components of this vaccine – ALVAC (which contains a modified canarypox virus) and AIDSVAX – have been shown to offer no significant protection when administered alone.

Commentary on the full report is already being written of course (by people paid to do it, unlike me…) with the interesting points that vaccine efficacy may not only fall after the first year following inoculation but also seems to have a higher efficacy in trial members who are in low risk groups.  The point is an obvious one – a whole bucket more questions have been raised by this trial than have been answered. Even if we cautiously accept the significance of the findings and that the vaccine’s efficacy is real, we have sod all idea why or how.

But, as disheartening as this may sound, particularly to those people who have watched every other HIV vaccine project attempted over the years fail, this is certainly a positive finding. The reason for this is that in terms of how science is done and applied, the methodology doesn’t exist in a bubble. When important things like vaccine work get noticed, they also get noticed by activists, journalists, politicians. Policy can be affected, along with public opinion which can have more affect on an academic enterprise than may be obvious.  Funding into HIV vaccine research has been dropping which obviously has not been helped by all round economic belt-tightening at the moment, so this study may provide a much needed boost to a previously bleak field. Awareness is also raised amongst those people who sign the cheques. The global vaccine market is big money whichever way you look at it, though obviously investing in 16,000 strong trials that span years with no product to show at the end of it makes a sad face for any investor who might think it purely profitable. Big cash source, big cash sink. This study is the first indication that work on an HIV vaccine might not just be the latter. Many HIV activists are likely to want to push this too, as the head of IAVI Seth Berkley says:

Years of investment and dogged science are providing leads for solving one of today’s most pressing research challenges. Some 7,400 new H.I.V. infections occur daily throughout the world. Clearly we need better methods of preventing the spread of H.I.V., and no public health intervention is more powerful or cost-effective against infectious disease than a vaccine.”

Though cautious optimism should be present for communicators and advocates this is definite justification that HIV vaccine research is not flushing cash down some impossible non-route. it is a long and tricky path…but finally, a little evidence that it is a path. Paths have ends!

Further reading:

http://www.voanews.com/english/2009-10-20-voa35.cfm

http://www.earthtimes.org/articles/show/detailed-results-from-rv-144,1005065.shtml

http://www.voanews.com/english/Africa/2009-10-20-voa38.cfm

http://www.marketresearch.com/product/display.asp?productid=2284570

Oct 15
Posted by: nicholasswetenham  

Blog Action Day 2009

What can conferences achieve? Why do we go to the great expense of holding them?

I have been to two conferences in two weekends, and they could not possibly have been more different.

TAM London 2009 was a meeting aimed at humanists, skeptics, scientists and atheists. There were many notable, highly entertaining speakers – from the cause célèbre Simon Singh to comedians like Tim Minchin. For the privilege of seeing all of these speakers in one go, guests paid up to £200, with discounts of only £10 for students or members. It was incredibly entertaining and perhaps gave some sense of community to people who do not otherwise bond based on their beliefs. However, from what I could see it ultimately served as a fundraiser for the James Randi Education Foundation, a non-profit which seeks to educate the public about pseudo-science. With this money, it will pursue its aims

Power Shift 2009 (London), on the other hand, was a conference organised by the UK Youth Coalition on Climate Change. It cost about £20 to attend. There were talks held throughout the weekend – but usually aimed at young people with short attention spans, lasting no longer than 15 minutes, and aiming to inspire or lead by example. Over the course of the weekend, participant learned campaigning skills based on public narrative, and bonded in gradually larger groups through the use of story-telling. It was very 2.0 – training plus inspirational examples plus social networking, all in one weekend. It culminated in a day of action this Monday, with flash-mobs on the South Bank and in Parliament Square – video here and Guardian coverage here. Not only did this generate a media-friendly campaign action that generated decent press coverage, the shared experiences of the weekend can be built for future action. In my mind, this is a far more effective and lasting way to use a weekend of like-minded people coming together.

So to those of you organising conferences, take heed: tapping into the networking aspect of conferences, usually reserved for corridors and coffee-breaks, can lead to an entirely different experience for attendees and a lasting effect.

Aug 06
Posted by: nicholasswetenham  

Geeks among you might be familiar with TED, a series of conferences that started 0ut very tech-oriented but now deals with everything including complex global issues and cutting-edge science. Its motto is ‘Ideas worth spreading’. I used to be a big fan when I discovered that they made their talks public under a limited CC license. You can watch about 500 of them here. After a hardcore science talk by someone with no public speaking skills poring over reams of data in excruciating detail, these seem like a breath of fresh air.

But on closer inspection, I found that TED has two major issues:

1) Dumbing down. The flipside of the ’simple is beautiful’ 20-minute time limit and lay demographic, which makes the talks so accessible, is usually oversimplification of an issue or one-sidedness.

2) Dramatisation. They seem to love ‘revolutionary ideas’ (see how often that pops up in talks descriptions). Sadly, science and technology are not solely sudden breakthroughs by crazy geniuses. These geniuses require the more prosaically heroic work of tens of thousands of hours of plodding by unsung everyday scientists, and they are often wrong. As it turns out, crazy ideas are often just that.

TED, to its credit, doesn’t make any claims about the veracity of the claims but it does give people a shared platform with former US presidents, serving prime ministers, Bill Gates, and various Nobel laureates. That’s one big springboard.

So have they been over-promoting fringe scientific theories? Well they do feature repeated appearance of Craig Venter and Kary Mullis both of whom are mavericks with odd views when they stray from their own expertise (Mr. Venter wanted to use the reference human genome for commercial gain and Mr. Mullis is a global warming denialist and an AIDS denialist. Note the armchair.)

And then there’s this recently published talk. It’s Elaine Morgan, a distinguished writer and Oxford graduate who has been a strong voice in the feminist movement. She is defending the Aquatic Ape Hypothesis, which other than writing and the feminist cause is one of her great interests. It broadly refers to the idea that certain unique feature of humans among primates such as our thinner hair, and perhaps even bipedalism, can be explained by a history of aquatic or semi-aquatic life after the chimp-human split about 5 Million years ago. As she outlines its, it sound really neat. It also has a certain romance. But note that she doesn’t discuss the evidence, just complains that it has ‘never been properly looked at’. She also uses an argumentum ad Davido Attenburgo. It has been, and is generally considered seriously flawed for multiple reasons. There is Oreopithecus, a swamp-dwelling extinct (partially?) bipedal primate which would be nice as supporting evidence but we don’t really have anything that relates to the human lineage.

Those who know Colin well know that Evolutionary Biology frustrates him mightily, for while its foundation is strong the minor specifics that acadamics spend most of their time quibbling over are often debated in a hypothesis-rich and experiment-free context. This is because evolution is difficult to experiment on since it operates on geological timescales far greater than a scientist’s lifetime. This results in what he calls ‘armchair science’: sitting back in your gown with a pipe and saying “Well, I think this explanation is the more sensible-sounding one, don’t you old chap? Hurrah, we’ve cracked it. Open the port, would you Jeeves?”

Much to his satisfaction, I’m sure, both Kary Mullis denying global warming and Elaine Morgan discussing a fringe theory of human evolution is done from a seated position.

In short, TED has given a lot of publicity to a hypothesis which probably did not merit it. For some serious discussion of the actual science, people far cleverer than me have discussed it on the blogosphere recently, presumably in response to questions arising from TED publicity. Highly recommended reading:

Greg Laden of Scienceblogs

Jim Moore’s comprehensive critique

***Edit 07/08/2009***

Oh, and so that I don’t bash TED too much, here is one excellent TED talks by Hans Rosling - the one that originally got me hooked:

Hans Rosling on the developing world

With the infinitely powerful lens of hindsight I now see that this is because he shows data. Lots and lot of it. In fact he has to talkveryfast and use an animated data visualisation tool to be able to present all of it in 20 minutes. Without these added bonuses, the amount of data in most TED talks is minimal.

Jun 28
Posted by: colinhockings  
Green Tea (Wikimedia Commons)

A BBC article on a study (PubMed) by a group, led by Dr. James Cardelli at the Louisiana State University Health Sciences Center, reports that green tea extracts slow the progression of prostate cancer. It has also been reported on by Reuters and (briefly) in the Daily Mail, as well as various blogs such as Attorney-at-Law and BloggingStocks and a health information network that seems to focus on alternative medicine called HealthNews.

The study itself is not perfect. They took 26 patients with stage I, II or II prostate cancer who were scheduled for radical prostatectomy (removing the prostate) and gave them a high dose of polyphenon (a green tea extract marketed by Polyphenon Pharma) until the day before the operation. As the most important outcome (survival) is hard to measure, especially in a single-armed (i.e. one group) trial like this, they measured serum biomarkers (signalling molecules in the serum) that seem to correlate with prostate cancer progression: HGF, VEGF, PSA and the IGF-1/IGFBP-3 ratio before taking the pills and before surgery. They mention the small sample size and lack of a control group but don’t, to my mind, make these limitations clear when they discuss their results. There’s nothing wrong with it, as a purely preliminary trial, but it is very poor evidence. The American Association for Cancer Research (AACR, the body that published the study) press-release has a very important statement about this which was left out of all the reports I’ve seen on this study:

William G. Nelson, V., M.D., Ph.D., professor of oncology, urology and pharmacology at the Johns Hopkins Kimmel Cancer Center, believes the reduced serum biomarkers of prostate cancer may be attributable to some sort of benefit relating to green tea components.

“Unfortunately, this trial was not a randomized trial, which would have been needed to be more sure that the observed changes were truly attributable to the green tea components and not to some other lifestyle change (better diet, taking vitamins, etc.) men undertook in preparation for surgery,” added Nelson, who is also a senior editor for Cancer Prevention Research. However, “this trial is provocative enough to consider a more substantial randomized trial.”

This is the most sensible thing I’ve read about the study, clearly summing up the fact that while there may be an effect, this trial doesn’t show it at all convincingly. It also occurs to me that the samples from before and after treatment were all run on the same ELISA, i.e. the sample from before the treatment was stored at -80°C for between 12 and 214 days longer than the second sample. This may not be a problem, but I didn’t notice any acknowledgement that the researchers considered it. This is why we need control groups! With more participants and a control group you could say ‘well…they might have changed their lifestyles and some parts of the serum may be destroyed by cold and Mercury may have entered Vesuvius, but the treatment group still shows a benefit”. Clearly, such a preliminary trial is not worthy for publishing on its own, so the researchers also tested the safety of such high doses by measuring the liver function (verdict: safe) of the 26 patients and an in vitro study of fibroblast cells treated with EGCG (epigallocatechin gallate, the most common catechin in polyphenon).

Regarding the BBC article itself, I noticed three errors that are quite revealing:

  1. It claims that polyphenon is a compound, which it is not. It is a complex extract from green tea leaves. This is the difference between buying a stack of bricks from the manufacturer and bulldozing a house – a compound is quite pure, while a complex mixture has many unknown components. While not necessarily important to the story, this mistake somewhat undermines my confidence in the scientific literacy of the author.
  2. The location of the study was given as Philadelphia – the address of each researcher (all in Louisiana) is given on the first page of the study. Where could this mistake have come from?
  3. The age range was given as 41-72, but the original paper seems to think it was 41-68.

The age-range of 41-72 also appeared on the Polyphenon Pharma blurb about the trial, published a few days later. The source of the discrepancy: the press-release from the AACR. The 41-72 age range was presumably a typo – if they knew the original article to be incorrect they would presumably correct it: it hasn’t even been published on paper yet.

Imagine my surprise when I re-read the first paragraph of the press-release:

PHILADELPHIA – According to results of a study published in Cancer Prevention Research, a journal of the American Association for Cancer Research, men with prostate cancer who consumed the active compounds in green tea demonstrated a significant reduction in serum markers predictive of prostate cancer progression.

So THIS is where the ‘Philadelphia-based researchers’ comes from – the press-release was written in Philadelphia. And, if we look closer, the first paragraph might also be the source of my other gripe: the ‘compound called Polyphenon E’. I may be wrong, but it seems to me that the author of the BBC article simply read the press release and regurgitated it, without ever taking the time to read the original paper. To be fair, though, I maintain my faith in the BBC News service to some degree because this lax effort was clearly not sufficient. The author got a statement from the head of the Prostate Cancer Charity – a modicum of journalistic investigation was performed, even if it began and ended with a call to the most relevant charity.

The Reuters article is a little better: it has the correct location and age range, and has some extra statements from the lead researcher, James Cardelli. There is nothing to indicate that the author read the original paper, but at least there were no glaring errors. In addition, it finishes with the observation that it ‘was a small trial and bigger studies would be needed to confirm the results’. The only thing I take exception to is the claim that the patients took the pills for ‘about a month’ – while the median duration was 34.5 days, the maximum was 214 days (although that was a special case – the next longest duration was 73 days) and the minimum was 12 days. I guess I may just be hard to please.

In conclusion: while I think it would be good to keep an eye on green tea as a potential supplement to cancer treatments in the future, this study is not the shining beacon that proves it. For a more balanced appraisal of the evidence then you’ll find in the media, I recommend searching PubMed for metastudies and literature reviews. As I expected, they mostly seem to say that while the pre-clinical (on cells in culture and in model organisms) research looks compelling, there haven’t been enough large, good-quality trials to show anything particularly significant in humans.

P.S. If you are a cancer patient and the sketchy evidence on the benefits of green tea make you decide to drink lots of it, first consider: a) green tea has caffeine – some studies of green tea showed a lot of side effects that were presumably due to the caffeine, and b) EGCG may interact with some cancer drugs, especially Velcade (bortezomib) so consult with your doctor. In general, it is a very bad idea to attempt to treat yourself with the preliminary results of trials of unlicenced treatments. They are unlicensed because their effectiveness, and more importantly their safety, isn’t known.

ResearchBlogging.org

McLarty, J., Bigelow, R., Smith, M., Elmajian, D., Ankem, M., & Cardelli, J. (2009). Tea Polyphenols Decrease Serum Levels of Prostate-Specific Antigen, Hepatocyte Growth Factor, and Vascular Endothelial Growth Factor in Prostate Cancer Patients and Inhibit Production of Hepatocyte Growth Factor and Vascular Endothelial Growth Factor In v Cancer Prevention Research DOI: 10.1158/1940-6207.CAPR-08-0167