Tracking down genes involved in Alzheimer’s disease

Alzheimer’s disease (AD) remains the most common form of dementia, particularly the late-onset version which typically develops in patients aged over 65. Although there is believed to be a strong genetic basis to the disease, the only gene previously identified as a susceptibility factor in all version of the disease was APOE, coding for Apolipoprotein E. In addition, genes for Amyloid precursor protein (APP), Presenilin 1 (PSEN1) and Presenilin 2 (PSEN2) have been noted as factors in the less common early-onset form of AD, which has a strong pattern of familial inheritance. Other attempts to find genes influencing the more common late onset form of AD have been ‘under-powered’, i.e. have involved insufficient individuals (≤1,100) to reveal any further statistically-significant correlations.

In October 2009, however, two independent studies published “back-to-back” in the journal Nature Genetics identified a number of other genes in which Single Nucleotide Polymorphisms (SNPs) seem to be associated with development of late-onset AD.

How widespread is scientific misconduct?

From time to time examples of scientific fraud come to light and raise questions about the integrity of scientific endeavour. The most well-known example of recent years must surely be South Korean stem cell biologist Hwang Woo-Suk, whose ground-breaking discoveries in the field of therapeutic cloning were exposed as bogus (In addition to his science reputation being in tatters, Hwang was convicted in October 2009 of embezzlement and violation of bioethical laws, although he escaped a custodial sentence).

In physics, the multiple re-use of the same graphs as data for entirely different experiments led to the downfall of a leading young nanoscientist (this was the subject of a 2004 episode of the BBC’s Horizon series The dark secret of Hendrik Schön). Are Hwang and Schön rare examples bringing unwarranted criticism to a body of otherwise exemplary scientists, or are their crimes indicative of much wider malpractice within the scientific community?

University of Edinburgh researcher Daniele Fanelli has shed some light on the the extend of scientific fraud in an article How many scientists fabricate and falsify research? A systematic review and meta-analysis of survey data. Published in the open access journal PLoS ONE in May 2009, the research brought together data from a number of earlier smaller studies on scientific misconduct to generate “the first meta-analysis of these surveys” (p1).

Science on the Telly: “And the winner would be…”

At the risk of sounding like a Carlsberg advert, “The Journal of the Left-handed Biochemist doesn’t do award ceremonies, but if we did…” – what would be the winner of “Best Science programme” during the last 12 months?

In truth, I think it has been a bumper year for science programmes. There has been a tangible return to form at Horizon – the first three episodes of the current series, for example,  have all included significant coverage of molecular biology. There were commendable features to the mini-series Prof Regan’s Diet Clinic/Medicine Cabinet/Nursery/Health Spa (I have posted a separate review of Prof Regan’s Medicine Cabinet here) although it did let itself down at times by commiting some of the same mistakes it was accusing others of making. Pitched at a slightly different audience, it is also good to welcome Bang Goes the Theory to finally fill a gap in popular science coverage left empty since the demise of Tomorrow’s World around 2003.

Preparing for Med School interviews

The following are notes written for a session I was asked to run with sixth form students about preparing for Med School interviews. I am quite sure there are lots of sensible suggestions that I have inadvertently omitted – please feel free to use the Comments facility to offer your additional advice.

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Your personal statement: You’ve got an interview! Apart from anything else, that means you must have done something right in your personal statement. Even though it may be months since you wrote it, it is important that you re-read it thoroughly about a week before the interview to remind yourself what you said and then reflect on what questions this may lead onto. In particular, think about:

• What did you learn via the experiences you described? You’ve probably used time spent shadowing or participating in medical activities as part of your statement. You may also have mentioned a part-time job or being captain of a sports team. Your interviewers will not so much be interested in what you’ve done as to what you’ve learnt by the experience. For example, how have your attitudes been altered? What was it about the things you’ve been involved in that makes you more suitable to be a doctor than the next person waiting outside?
• Can you provide evidence for the claims you made? I am assuming that all the things you said on your UCAS form are true (if not, you are just setting yourself up for more problems – be warned, don’t make stuff up). There is, however, a difference between you yourself knowing something to be true and being able to demonstrate that to somebody else. Let’s take an example from my wife’s experience. She wrote on her UCAS form that she was a keen dress-maker. Somebody wisely pointed out that if she was going to put that in her statement then she ought to wear something she’d made when going for interview. It was good advice; at every interview she attended somebody asked if she’d made the clothes she was wearing. If you are not yet in the habit of collecting documentation to back up work experience, Saturday employment etc then start now – portfolios of evidence are a fact of life in lots of jobs but none more so than Medicine, where even Consultants need to log their Continuing Professional Development (CPD) activities.

Add something “sciencey” to improve your plausability

There are many reasons why I am grateful to have spent some of my summer reading Ben Goldacre’s excellent book Bad Science, including the fact that it brought to my attention a paper The Seductive Allure of Neuroscience Explanations. The article is an account of experiments conducted by Deena Weisberg and colleagues at Yale University, and was published in the Journal of Cognitive Neuroscience in 2008.

Recognising that neuroscience is an area of research that fascinates the public and where discoveries are frequently picked up by the general press, Weisberg et al generated four explanatory statements for each of 18 different psychological phenoma. In each case the four statements represented:

• a good explanation without specific mention of neuroscience
• the same good explanation with the addition of plausible, but logically irrelevant, neuroscientific details
• a bad explanation without specific mention of neuroscience
• the same bad explanation with the addition of the same plausible (but irrelevant) neuroscience as in the second example

You know when you’ve been viper-ed

A tweet this morning from @jon_scott alerted me to the fact that sometime over the weekend, the University of Leicester has been visited by the PR machine for the Viper service. Paving slabs had been stencilled with the company’s logo and web address. Rather ingeniously, the marketeers have jet-washed the image rather than painting it on, which I presume guards them against accusations of vandalism because all they’ve actually done is remove dirty (thanks to @jobadge for pointing this out, she is obviously more ‘direct action’ savvy than me). The image on the bumpy pavement at the traffic lights makes the wash v paint strategy most clearly.

Viper is marketing itself as a way for students to check that their work is not guilty of plagiarism. Several institutions have already wrestled with the question of whether to let students pre-submit their work to Turnitin so that they can see for themselves if it is going to get pinged by that software with the same intentions. However laudible this seems, one of the difficulties is the fact that students will simply learn how to mask their tracks rather than developing bona fide study skills. The subversive nature of the current marketing strategy reinforces the view that this is a way to “beat the system”. I was interested also that one of the recommendations for the software on the Tucows site seems to come from a student who bought a ‘bespoke’ essay for her course and was now asking for a refund as the software showed it was not quite the original work she thought she’d paid for!

Making the best of “Bad Science” (Review)

Harper Perennial edition (2009)

If you have not yet read Ben Goldacre’s book Bad Science, then I thoroughly recommend that you do. As readers of his regular Guardian column or his website will already know, Goldacre has embarked on a campaign to root out example of pseudoscience and shoddy science whereever they may be found.

All the usual villians are present – homeopaths, nutritionists, slack journalists, pharmaceutical companies and AIDS dissenters. Some are mentioned by name, but given their alleged predilection for litigation, and since I do not have the time, the money or the inclination to do battle with them in the courts, I shall not repeat their identities here!

It would be wrong, however, to give the impression that Goldacre is merely on a crusade against high profile exponents of “bad science”. True, the author does sometimes betray a little too much glee as he places a bomb under the throne of a media ”health expert” (in a way that I found disturbingly reminiscent of the Physiology lecturer, when I was a first year undergraduate, recalling his boyhood experiments on frogs). Nevertheless, Goldacre is keen to emphasise that his purpose is to “teach good science by examining the bad” (p165 in my copy), adding that ”the aim of this book is that you should be future-proofed against new variants of bullshit” (p87).

“Will this be in the test?”

Amongst the major science research journals, Science magazine has consistently been the most prominent in flying the flag for science education. I was very interested, therefore, in an Editorial by Carl Wieman in the September 4th 2009 issue of the magazine. In his piece Galvanising Science Departments, Wieman describes some fairly radical innovations in Science Education currently underway at the University of Colorado and the University of Bristish Columbia. The aim is to adopt evidence-based teaching methodologies with emphasis on the development of scientific thinking and problem-solving skills rather than fact regurgitation.

I have no direct experience of teaching in the USA, either as provider or recipient. I know, for example, that much greater emphasis is placed on the recommended course text in the USA than in the UK, but beyond that I cannot speak with any authority. It does sound like some of the reported innovations are things that have taken place here for some while, such as the addition of specific (skill-centred) learning goals to modules. A cornerstone of the strategy has been appointment of science education specialists, individuals who not only have expertise in their subject discipline, but are also au fait with educational and cognitive psychology studies, a variety of effective teaching strategies and – I note with some mirth – possess diplomatic skills!  The programme is ongoing, the University of Colorado is in the 4th year of an initial six year project and so the full impact of the developments will not be known for some while.

CiteULike = SiteILike

I have been a devotee of social bookmarking tool delicious since 2007 and now have nearly 4000 items tagged. Although the ‘before’ and ‘after’ photos (slide 17) in my July 2008 presentation Knowing where it’s at: find it? flag it? share it? (or how delicious saved my life) were staged for effect, the ability to accumulate links to resources online rather than generate piles on (unread) papers in my office has been a genuine revelation.

Alongside delicious, I also dabbled briefly with Connotea, the online reference management tool from the Nature stable. It has the same potential as delicious for user-generated tags, but at the time I couldn’t really see what additional value it was adding and I let my interest wither, electing instead to use delicious alone for all of my bookmarks, including journal articles.

More recently, I’ve been persuaded by a colleague to take a close look at rival social citation application citeulike. This time around I think I get it. One of the features that really appeals is the potential to import comprehensive bibliographic information armed only with the Digital Object Identifier (DOI). With journals making the DOI of articles increasingly obvious on their websites and in table of contents alerts, this becomes a very straightforward way to collate large quantities of metadata whilst retaining the capability to tag a paper with whatever keywords reflect its relevance to you.

In truth, I have not conducted a rigorous side-by-side comparison of citeulike v connotea (or any of the other similar tools). I am quite sure, for example, that they all have the potential to assimilate bibliographic details armed only with the DOI. For the foreseable future I will continue to tag journal articles using delicious. However, this feature of citeulike, couple with the capabililty to establish shared libraries of articles relevant to members of a particular list, has persuaded me to also give the latter a prolonged trial.

Are you good at multi-tasking? Are you sure?

I was intrigued by a recent paper Cognitive control in media multitaskers in the highly-regarded journal Proceedings of the National Academy of Sciences. The study looked at the information processing styles of self-reported media multitaskers, defined as users of two or more content streams simultaneously, compared with those who do not multitask in this way. (I will skirt over the irony both that I was supposed to be doing something else at the time I spotted the BBC report of the research, and that my son has just switched on the TV as I type this review on my laptop.)

An electronic copy of the paper was posted online in August 2009, ahead of publication in the print journal (doi: 10.1073/pnas.0903620106)

In their research, Ophir et al asked 262 University students to complete an online self-assessment questionnaire regarding both the total number of hours spent using different media (they specified 12 formats including TV, online video use, music, print media, e-mail and text messaging) and how likely they might be to use some of these concurrently alongside a primary task. The authors then generated a numerical Media Multitasking Index (MMI) and ranked the students. Those with a score one or more standard deviations below the mean (light media multitaskers, LMMs) or one or more SDs above the mean (heavy media multitaskers, HMMs) were then invited to participate in a series of cognitive ability tests. In total there were between 30 and 41 students taking the various tests, evenly split between LMMs and HMMs.