Science Books...

One of my Chimmz gifts this year was a wonderful gift card to Canada's largest book retailer, the Indigo Corporation. Before I discovered Amazon's amazing prices, Indigo and its subsidiary, Chapters, were one of my favorite haunts. I returned there today hoping to stock up on a few books for the upcoming frigid months.

My reading output certainly dropped in 2010; in fact it's been in a steady decline for a few years. I think that moving further into my career in science has necessitated more work-related reading, causing reading for pleasure to suffer. However, I've begun reading quite a bit again during the past few months, mostly because I've shifted back to my favorite genres - pretty much everything non-fiction1.

With this in mind I began perusing the 'science' section, looking for a few recent volumes. Is it just me or are many 'science' books insanely misleading? The way I see it, there are 2 travesties of the science section:

1. Pseudo-scientific garbage, much of which seeks to combine obscure biblical prophecies with complicated physics.

2. Questionably supported, almost entirely hypothesis based books with shockingly misleading titles/subtitles (Things like 'How the Brain Works' or 'How Adaptation Explains Everything'). 

Honestly, I don't know which ones are worse. Category #1 really doesn't even belong in the science section, and they're pretty easy to avoid if you know anything about the subjects you're browsing. Note that I place a harsh emphasis on that last part of the previous sentence - I don't know to what degree lay people are taken in by these books. Perhaps category #2 is more insidious because, on the surface, these books tend to appear more legitimate: they're often written by folk with credentials and they definitely sound interesting. I always have the same reaction when I see them too: "Wow, wish someone had told the scientific community that we know exactly how the brain works, or that fire, or music, or disease is THE reason behind human intelligence and behavior". Since these topics are obviously so well understood, we can probably stop pumping money into researching them.

I had an interesting conversation with a buddy some years back during which he asked why scientists don't form a representative body that 'vets' books. Not an organization that determines whether the view/hypotheses espoused in the books are correct, but rather one that would put some kind of seal on books that were actually based on science and peer-reviewed research. Logistical and financial issues aside, I'm not sure that an organization like that would work: disagreement really is a big part of science. It's difficult to get the field to see eye-to-eye on any number of current controversies, and some of us actually view entire fields as pseudo-science (you know, a lot of those category #2 books are from the field of evolutionary psychology...).

Oh well, what's a scientifically interested lay-person to do? I suppose that scientists can continue to write book reviews in the popular press trying to promote the good and discredit the bad. Any other ideas? 

1When I was young, I read fiction exclusively, often struggling to read anything related to 'RL' (real life). Now it's the complete opposite. For me to read fiction, the book has to be something special, such as a classic, or related to some topic of interest (e.g., one of the books I picked up is Robert Heinlein's Stranger in a Strange Land).

Home for the Holidays: A Potpourri...

A few days ago I made the trip from Washington, D.C., USA to Moncton, N.B., Canada by way of Montreal. The trip was relatively uneventful, with the sole exception that the landing in Moncton was just about the most turbulent I've ever experienced.

Said turbulence came from the hurricane force winds and rain that have been buffeting Eastern Canada, causing flooding and general property damage. Thankfully, my parent's place is a good 30 km (18.6 mi) from the waterfront, where the worst of the damage is occuring. It's unheard of to see rain at this time of year, but hurricanes are ridiculous. Apparently this part of the country has been getting severe weather all through December.

I've spent the past couple of days getting to know my parent's crazy little Shih-Tzu, Miko, who they've had for a couple of years, but got long after I moved away:

I know there's nothing the dog can do about it, but the thing looks perpetually depressed and it's kind-of heart-wrenching (Shih-Tzus' eyes water continuously, which makes it look like they're always crying). Miko's also the most neurotic thing I've ever met. He won't eat from his bowl because the sound of his bowl scares him, the sound of the ice-maker in the refrigerator terrifies him, heating grates terrify him, and if he drops a toy on them he'll start crying (audibly) until someone goes and picks it up. We're talking 6 x 12" grates here! Did I mention that my folks can't buy him squeaky toys because they scare the bejesus out of him? Weird.

Thankfully it snowed this morning, so at least Chimmz will be a little white. The weather is still quite mild and well above freezing, so it's unlikely that there'll be snow by tomorrow morning. Still, it's 'purrty':

Finally, I've finally had the chance to pick up some French books for the purpose of brushing up on the old maiden language. Specifically, I've wanted to read Voltaire's Candide in its original French for some time now, so I picked up a big omnibus of his work. I'm sure I'll blog about it at some point in the future!

Comment connaît-on qu'on est dans une librarie Canadienne?

More to come as the holidays continue!

Mini Journal Club: Alternative Splicing...

A topic in which my postdoctoral research has caused me to become more interested is that of alternative splicing, or the process by which cellular machinery can mix-and-match alternative regions of expressed gene-coding DNA in order to create multiple different proteins (called 'isoforms') from a single gene1. Although we've known about alt splicing for a long time, and it is intricately involved in some pretty important processes (sex-determination in Drosophila occurs via a cascade involving multiple alt splicing events), it's traditionally been fairly difficult to study. It's not until recently that we've developed techniques allowing us to interogate the entire genome for alt splicing events, probably the most popular at the moment being RNA-Seq, or the direct sequencing of all expressed regions of the genome2.

With that brief introduction, I'd like to note that alt splicing, or more specifically its scope and frequency, has been somewhat controversial for the past several years. Early attemtps to assess the overall degree of alt splicing in the human genome suggested that somewhere in the range of 94% of genes capable of being alt spliced (e.g., those with introns) did, in fact, show evidence of having multiple isoforms. However, this seemed to create a bit of a problem because some (perhaps many) of the genes found to be alt spliced had been studied extensively at the protein level, and no evidence for alternative isoforms had been detected. Thus, was all of this alt splicing detected in expressed genes noise, or perhaps these alternative were isoforms not producing proteins but rather had some significant regulatory function?

An interesting paper examining alt splicing in humans has provided evidence that much (~50%) of this alternative splicing is, in fact, noise generated by imperfect cellular splicing machinery (Pickerell et al. 2010). Many splice junctions (the junctions were bits of genetic code are 'pasted' together in order to form protein coding transcripts), including some involved in alt splicing, have been detected and annotated using traditional, arguably less-sensitive-than-current means. New techniques such as RNA-Seq have detected many, many more junctions, however most of these are derived from very low abundance isoforms, consistent with a constant low-level of splicing errors. Furthermore, the new, low abundance junctions show low degrees of evolutionary conservation in other primates - unlike the previously annotated junctions - consistent with their not being actively maintained by selection due to lack of functionality.

We haven't yet managed to decode the entire set of rules that determine exactly how transcriptional machinery figures out which isoforms to produce, but we do have some understanding that it is controlled by signals encoded in genomic sequence. Some of these signals are short enough (a few nucloetides) such that they can probably arise quite frequently by chance through the process of random mutation. Thus, some number of 'cryptic' splice signals are present in the genome at any one time, leading to the generation of incorrect (and likely ultimately degraded) transcripts. From their data, the authors of the study estimate an error rate of approximately 2%; about 2 times out of 100 splices, the machinery gets it wrong and pastes non-functional regions of the genome into genes. Disturbingly, this 2% of incorrect splicing may account for ~50% of the splice junctions detected by modern short read sequencing techniques.

I enjoy studies that use elegant and straightforward methods to address burning questions - especially when those questions potentially involve controversies that can create a lot of work chasing ghosts3. I hope to highlight other interesting papers in the future - especially those like this one, that are open access and thus open to everyone. It seems like a good way to discuss what I do without actually having to describe what I do!

1There are probably molecular biologists that are tearing their hair out from this simplified description, but bear with me, I'm trying to write for specialists and non-specialists alike!

2I plan to have a blog post about the miracle/curse of high-throughput short read sequencing in the near future.

3Without going into it too much, there are often questions about how much sequencing (RNA-Seq) one needs to do to capture all of the information in a sample. Part of the conclusions of the study are that many of the low abundance transcripts - those that require more sequencing to capture - are the result of errors in splicing. Thus we may hit a point of diminishing returns in terms of sequencing 'depth' at  a quicker pace than we thought.

Pickrell JK, Pai AA, Gilad Y, Pritchard JK. 2010. Noisy splicing drives mRNA isoform diversity in human cells. PLoS Genet 6:e1001236.

Busy, Busy Month...

I'd like to say that December has been an uncharacteristically busy month for me, but that would be a lie. Rather, it's been quite characteristically busy. I'm flying home to good 'ol Moncton, New Brunswick, Canada, for a 9 day 'Chimmz'1 break, and needed to get a lot of little odds and ends done in the lab before leaving. Flies, for instance, generally dislike being left to fester in old food for ~1.5 weeks, so it's best to give them fresh media just before leaving.

Despite my best efforts, work continues to pile up. I'm trying to redo some analyses that I performed last summer so that I can put together a manuscript that's fit for publication. Sadly, I'd already abandoned trying to publish this thing last summer; upon further reflection however, our group has come to the conclusion that it deserves another (better) shot. I'm also in the process of writing a book chapter for an upcoming volume on rapidly evolving systems. In many ways this chapter is going to be an updated review of some of the major topics that I investigated during my Ph.D. Unfortunately, I've been hitting some serious writer's block, but I'll take the manuscript with me over the break - hopefully I'll make some headway on it.

Lastly, I spent the majority of the summer contributing to a big multi-lab collaborative project (the Model Organism Encyclopedia of DNA Elements, or ModENCODE) and the fruit of my labors has finally manifested itself as internal co-authorship in two manuscripts (one in Nature and one in Science). Both have been accepted and are supposed to be published before the end of the year, so I'll have details here when they become available!

I have a few ideas for things I'd like to blog about, none of which involve arsenic! So stay tuned.

1For any new readers of the blog, Chimmz is the non-denominational holiday that I celebrate during the Xmas time frame. It basically involves getting together with friends and family and being thankful (to no one in particular) for their company. The name 'Chimmz' has a nice ring to it, I think. Rolls right off the tongue!

Book Club: Classic X-men Vol. 1...

I wasn't really all that into comics as a kid, mostly because I thought they were too expensive (I seem to remember monthly issues costing somewhere in the $3.75 - 4.50 range, which is pretty pricey on an allowance). The only series that I can remember buying regularly for a few year were X-men and Uncanny X-men, which, in addition to the cartoons, I enjoyed a lot.

I pretty much ignored comics entirely until the end of my M.Sc., when I began picking up a few select books. It's really during my Ph.D. that I began reading graphic novels with more gusto, specifically due to the recommendations of some friends as well as some podcasts whose host's opinions I respected. One of the things that I quickly learned was that there's a whole world of graphic novels outside of superhero comics, and that many of these series (e.g., Fables, Preacher, The Walking Dead, Sandman, etc.) are very well respected as works of literature - that is to say, outside of the comic book crowd1. And while I've read many excellent books that I'm sure I'll discuss here at some point - I recently decided to delve back into superhero comics in a unique way by picking up a collection of the very first 24 issues of X-men ever published.

If I understand my comic book lore correctly, X-men, originally published in 1963, came out during the 'Silver Age'. This period of comic history began after the industry self-imposed Comics Code Authority came into play in 1954, ending the long era of horror, crime, and suspense books thereby causing surviving comics publishers to return to superhero titles2. This period is also well-known for its strong undertone of 'bowdlerization' of story themes as the industry operated under an oppressive set of restrictions regarding what could and could not be depicted.

These early X-men comics are notable both for how early many of the most beloved heroes and villains in the series were introduced (for instance, I was surprised to learn that the iconic Sentinels appear by the 14th issue of the series) but also for how strongly they reflect the social norms of the time. While entertaining as a window into a period of America's history, the stories are about on par with the Archie comics I occasionally read as a kid, replete with the same degree of borish story book romance junk. Most of the villains and their schemes are laughable - fear the might of the Vanisher! - and there's very little controversy to any of the material... at least when judged by the standards of the time. The one thing that is quite surprising by today's standards is the shocking degree of misogyny in the books, so much so that certain panels are downright uncomfortable. The few female characters are regularly treated in patronizing tones that just wouldn't play in a modern setting. How times have changed!(?)

The only other thing I wanted to note specifically is how different the style of comic book writing was back then. To begin, every sentence ends with one to three exclamation marks, causing me to hear everything in my head in the voice of the announcer from the old Adam West Batman TV show!!! Also, there's an insane amount of text in every panel of the book: Not only do the characters explicitly describe each action that they're attempting, but every panel is also narrated, leading to an odd 'triple-redundancy'. Consider the following: A panel will show Cyclops destroying a wall using his 'optic blast'... while at the same time he says, "I'll use my optic blast to destroy this wall!!!"... and the box carrying the narration says, "The wall crumbles under the might of Cyclops' awesome optic blast!!!" Really? I wonder if Stan Lee was paid by the word?

I've already purchased the second collection containing the next 24 issues of the series, but I'm not sure if I'll go much further than there. Not only are superhero books 'not my bag', but I have to admit that there's not much here other than historical interest in where this now multi-million dollar franchise came from. I'd never claim that writers of the time were inferior to modern authors, but it's obvious that they were operating in a time where creativity was stifled due to the common perception that comics were harming youth psychologically. There's a spark of genius here in that the first hints of what would become the major theme of the X-men, 'mutants' as an allegory for racism, begin to make an appearance. I wonder how much different it would've been had Stan Lee (the famous creator of X-men, Spider-Man, The Fantastic Four, etc.) had full reign to explore any and all of his ideas?

1I should note here that there are actually some very good superhero books as well, such as Watchmen and The Dark Night Returns, but I find them more difficult to find amidst all of the drawings of large men flexing.

2I highly recommend an excellent book called 'The 10 Cent Plague' by David Hadju that chronicles the incredible rise in popularity of comics in America. This ultimately led to a large amount of unfettered experimentation by artists and writers and precipitated a government crackdown in the interest of 'protecting children'.