Field notes and the promise of science…

Read on below for my live-blog post on ‘Helga Nowotny on the promise of science’.

Live-blogging from the Nobel Dialogue conference was a new experience for me—the aim being to sit through a lecture/dialogue, digest the information, write a coherent and constructive blog post and then publish before (or while) heading to next discussion. Despite some thorough research prep ahead of the first day, and reading plenty of live-blogging advice about battery power and staying hydrated, I managed to arrive in the auditorium totally dehydrated, and proceed to deplete my macbook battery in 90 mins. Thus, my first post was executed by mobile phone on WordPress for mobile and submitted by sacrificing my attention to the next talk. Fortunately, the nice thing about having a team other other bloggers is that you know they have the next talk covered.

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Capturing Stockholm…

[This post was restored from a WayBackWhen archive. It was originally posted to a blog called ‘The Gene Gym” that began life on the Nature Network in 2010, and then moved to Spekrum’s SciLogs platform. Unfortunately many of the original images have not survived the import]

It’s amazing how far you can travel internationally before smelling fresh non-air conditioned air. I arrived at Arlanda airport – 50 km North of Stockholm – in the late afternoon, and was immediately siphoned into the familiar human corral of border security that is facsimiled the world over. The fastest route from the airport to the city centre is via the Arlanda Express, a name that evokes a surety of function that I’m willing to accept as a factual statement in this very modern Scandinavian country. Sure enough, in a mere 20 minutes I am delivered to Stockholm central station and can make my bid for the open air; yet emerging into a fog of -9C air was probably rather more fresh than I’d anticipated. Stockholm is seasonably festooned with lights, which twinkle in the crystalline cold and cast their light on streets paved with a compaction of snow, sand and salt, giving the consistency of gingerbread dough.

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An interview with Kerstin Lindblad-Toh, comparative genomicist…

[This post was restored from a WayBackWhen archive. It was originally posted to a blog called ‘The Gene Gym” that began life on the Nature Network in 2010, and then moved to Spekrum’s SciLogs platform.]

An important means by which we try to understand the human genome is, oddly enough, by looking at the genomes of other mammals. The aim is to identify areas of evolutionary constraint, regions of the genome that we all share (both coding and non-coding) and are thus likely to be important for all of these species. These regions have not only assisted with the identification and assignment of genes on the human genome, but they also provide important information about disease associated mutation. One mammal genome, unique amongst the others, offers particular insight into our genes and inherited genetic disease, the domestic dog.

The dog genome, published in 2005, was the fourth mammalian genome to be completed (after man, mouse and rat); the dog occupies a curious position in nature as it has shared a mutually beneficial relationship with humans for at least 15,000 years, living in the same environments as us and sharing our food. Over this time humans have selectively bred dogs for companionship, hunting, shepherding and other uses, and in so doing have channeled the diverse canine genome into a variety of behaviours, shapes and sizes.

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A Nobel weekend in Stockholm…

[This post was restored from a WayBackWhen archive. It was originally posted to a blog called ‘The Gene Gym” that began life on the Nature Network in 2010, and then moved to Spekrum’s SciLogs platform.]

On Saturday morning I’ll be rising at a hideously early hour to board the first of two flights that will (eventually) bear me on my merry way to Stockholm. I was lucky enough to be invited to be part of the blog team covering the Nobel Week Dialogue 2012, a new annual conference that will form part of the week of events leading up to the Nobel Prizes. I’m a big fan of conferences, I’ve lost count of the number I’ve been to over the years, but often classify them into two camps:

1. Specialist conferences: where I’ve gone to strut my academic stuff and watch others within my research community strut theirs – and when off the dance floor, we also listen to each other talk; and,

2. Geek/fan conferences, where you go immerse yourself with kindred spirits who share your interests, or where throw yourself into something new to learn and experience.

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Locked out…

On why a move to Open-Access publishing is a blessing, and a younger generation of scholars have little understanding of just how locked away knowledge used to be.

When I was an undergraduate you couldn’t get a journal article online, about the most you could hope for was a table of contents (ToC). Getting access to scientific articles meant a visit to the library with a photocopy card and a great deal of patience. ‘Bagging’ a photocopier was an artform in itself – I think everyone thought they knew of a secret, hidden photocopier on an upper level of the library, one that you felt you owned. Of course, this fog of solipsism would evaporate upon arriving to find your photocopier being used by another person. You would then resign yourself to waiting, staring indignantly at the interloper.

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My published negative result…

IMAGINE your excitement as a budding young researcher, taking on your first piece of research as part of an undergraduate summer studentship. The project is to characterise a gene that, within medically important bacteria, encodes resistance to a key group of antibiotics—the tetracyclines. The gene in question is described in a peer-reviewed specialist journal, but no-one is quite sure how the gene works.

So why are we interested? Well, if we’re to understand and address the problem of antibiotic resistance, one of the many things we need to do is understand their mechanisms of resistance—how they work. This gene appears very different from any other gene that performs a similar function, and because of this it has been classed into its own ‘family’ of resistance determinant which appears in reviews and textbooks. It has also been screened for, and found, in a notable ‘superbug’, VRSA (the vancomycin resistant big brother of MRSA). The presence of this gene may also have influenced whether or not a patient was given tetracycline because if a genetic screen comes back positive for a tetracycline resistance gene, then you’re not likely to recommend tetracycline (which may have been the preferred drug of choice).

The only problem is, the gene in question is not an antibiotic resistance gene, but we won’t know this until we’ve have spent the summer working on it. Indeed, it won’t be known until the project is inherited as a pet project by a postdoc. The fact is, the gene had already been recognised for what it was over a decade earlier, though this was ever reported. The person who immediately dismissed the gene’s published function all that time ago was in fact the one time PhD supervisor of the postdoc who picked up the project, and a world expert on the family of genes to which our mystery gene belongs, but I’ll come back to that.

My post last week, ‘On publishing negative results…‘, briefly described the issue of positive publication bias in scientific and medical literature, and was a pre-amble to the story of my own experience publishing negative results. So let me now tell you about how I tried, and succeeded, at getting ostensibly negative results published.

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On publishing negative results…

IN the last week Ben Goldacre’s ire has been felt, and rightly so, because what the Ire of Goldacre has been pointing at is a systematic bias in the publication of science and medical information. Ben’s focus relates to the way in which big pharmaceutical companies manipulate an overwhelmingly positive academic publication record, accusing them of selectively burying the results of negative trial data and publishing only the positive trial data. This serves the interests of pharmaceutical companies, but not those of the patients or doctors. You can see a video of Ben discussing this here.

The problem of publication bias in the scientific and medical literature is that positive results get published, and negative results – or those from studies attempting to replicate previous studies – by and large, don’t. There are several problems with this, and with which I’ve had practical experience:

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The ‘faecal’ bank…

Welcome to The Gene Gym on SciLogs.com.

I’m going to take great license to wander around numerous areas that overlap, nudge, cajole and nestle up against the main theme of my blog, which is of course bug and drugs.

So firstly, a brain dump:

A colleague and I once – rather drunkenly – planned a letter to The Lancet [a popular medical journal] in which we describe a means by which one might ‘bank’ a sample of ones faecal matter [shit] (comprising a cross-section of a healthy gut microflora), prior to departing on an exotic holiday, or undergoing antibiotic treatment. The premise was that any insult or injury arising from catching a bout of traveller’s Delhi-Belly, or depletion of the gut flora from chemotherapy, could be abated by having your original gut flora restored from your earlier banked sample. The service would naturally be called, the ‘Shit Bank’. Continue reading “The ‘faecal’ bank…” →

Re-awakening enemy sleepers…

The idea of an enemy sleeper agent is a central plot device in many a spy novel or movie, and certainly the idea of going to ground behind enemy lines is not unheard of in many theatres of conflict. The idea in all cases is to remain undetected until re-activated to cause harm behind enemy defences.

The trick to identifying if there are latent sleepers operating is to try and re-activate them and get them to reveal themselves. Cue any number of spy stories about false radio signals or targets to lure sleepers into the open.

Curiously, it is a similar strategy that is being used in novel treatments for infections from two disparate areas of chemotherapy, one in the treatment of HIV and the other the treatment of persistent bacterial infections.

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Where I am quoted not quite correctly….

I was recently called by an editor at NewScientist asking for some background on the field of fitness in bacteria, and particularly the issue of multi-resistant bacteria persisting in the environment (or clinic) in the absence of antibiotic selection. The reason for the question arose due to the upcoming publishing of an interesting paper in PLoS Genetics:

Silva RF, Mendonça SCM, Carvalho LM, Reis AM, Gordo I, et al. 2011 Pervasive Sign Epistasis between Conjugative Plasmids and Drug-Resistance Chromosomal Mutations. PLoS Genet 7(7): e1002181. doi: “10.1371/journal.pgen.1002181 “:http://dx.doi.org/10.1371/journal.pgen.1002181

Following this, I have been quoted in a NewScientist Health News item, and as I don’t feel my response is quite in the context I gave it, I thought I would give a more detailed account. I spoke to NewScientist last Wednesday (the paper in question wasn’t due to be published until the following day), but I was told that in the study the authors had observed that antibiotic resistance can have a positive effect on bacterial fitness, even in the absence of selection. I was asked whether this was a surprise to me, and more generally about research in bacterial fitness. What I perhaps should have done was ask specifically whether the paper was still embargoed and whether I could have more particulars of the study, because I could not have anticipated the particular nature of the study in question.

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