Womanspace – last lap.

I wrote a comment on Ed Rybicki’s blog, which is still awaiting moderation.  I’m not going to repeat what I said there, but I realized I had more to say than what I’d already written.  Specifically, I have much more to say about a comment he wrote on this article:

PS: “why publish something that you don’t believe in is another story” – no, it’s just that science fiction allows one to explore EVERYTHING, including what you don’t believe in.”

Ed makes a great point – Science fiction is exactly the right vehicle for exploring things that you don’t believe in.  Indeed, it’s been used exactly that way since the genre was invented.  You could say that Guliver’s Travels was a fantastic use of early science fiction, exploring a universe that mocked all sorts of contemporary idiocy that the author (Swift) disagreed with.

So, yes, I see Ed’s point – and he has a good one.  However, I’m going to have to disagree with Ed on the broader picture.  Science Fiction is perfect for exploring issues that you don’t believe in precisely because you can apply them to similar or parallel situations where they demonstrate their flaws.

For instance, if you want to write about how terrible apartheid is, you don’t set a science fiction novel in South Africa in the 1990’s, you set it up in on another planet where two civilizations clash – and you can explore the themes away from the flashpoint issues that are rife in the real world conflict. (Orson Scott Card explores a lot of issues of this type in his novels.)

The issue with Ed’s article – and there are plenty of them to chose from – is that he chose to engage with the lowest form of science fiction: Inclusion of some “vaguely science-like device” that casts no great insight into anything.  Science fiction, as a vehicle, is all about where you take it.

The premise would be equally offensive if he had picked: a race (“Filipino’s only get by because they have access to another dimension to compensate for their height”), a religion (“Christians use another dimension to hide from criticism leveled at their holy book”), or an age (“Anyone who can hold a job after the age of 65 is clearly doing so because they’re able to access another dimension”).

Ed could have made much better use of the vehicle he chose to drive.  He could have invented an alien species in which only one gender has access to a dimension, he could have used the alternate dimension to enable women to do things men can’t (and no, I don’t buy that men can’t shop efficiently) or he could have used his device to pick apart injustices that women face in competing with men.

Instead of using his idea to explore the societal consequences of the pllot device, he uses it to reinforce a stereotype.

That, to me, is not a good use of science fiction.  And the blame doesn’t just go to the author – it goes to the editors.  As a long time reader of science fiction, I can tell when a story doesn’t work and when it fails to achieve it’s desired effect.  This story neither worked, nor causes anyone to question their own values.  (It does, however make me wonder about the editor’s judgment in choosing to print it, as well as the author’s judgment in allowing it to be printed in a high profile forum.)

So, let me be clear – I despise the use of the sterotypes about women that Ed chose to explore. That he believes exploring gender issues this way is any less sensitive than race, religion or age would be is ridiculous – and shows a measure of bad judgement.

Having come up with a great tool (alternate dimensions) for making a comment on society (women and men aren’t treated equally), he completely missed the opportunity to use the venue (science fiction) to set the story in a world where he could have explored the issue and shown us something new.  In essence, he threw away a golden opportunity to cause his audience to ask deep questions and take another look at the issue from a fresh perspective – exactly what science fiction is all about.

Ed’s not a villian – but he’s not a great science fiction writer either.

Blogging about your own work.

Ok, so my titles aren’t nearly as inspired as Cath’s are.  This week hasn’t exactly been encouraging for puns, unless you consider massacring Danish pronunciation as a very complex linguistic joke.

Actually, I only have a glimmer of an idea tonight – but I’m writing because I need something to do to keep me up for an hour or so.  Sorry for the bad pun, but the clock *is* ticking and it’s only three weeks till I’m supposed to be in Denmark – and I still don’t have movers.  It’s driving me completely around the bend.  So, as a therapeutic device, I’m going to write my glimmer of an idea.  Please don’t be too harsh on it.

The idea for the post came from reading Jacquelyn Gill’s blog post, “Why did I start blogging?”  (By the way, please go vote for her to win CollegeScholarships.org Blogging Scholarship. She clearly deserves it!) Her post isn’t quite related, but at the same time, it is – you can go read it to see why, if you’re interested.

One of the things I struggled with for the past two years has been blogging about my own work. Of course, I interpret this as blogging about what you’re currently working on, not the stuff you finished months ago, which is always fair game.  (Blogging your own publications always struck me as blatantly endorsing yourself – something only politicians should need to do.)

Anyhow, blogging your own current work, showing the bumps and warts of science is something I love to do, and as a scientist, something I want to do as often as I can.  However, there are several problems with it.  It tends to tip your hand to the whole world about what you’re working on and that can have some disastrous consequences.

First, if you’re in a medical field, it can be difficult to talk about cases you’re working on, if there’s any form of patient confidentiality.  Many of the projects I’ve been involved in have required me to maintain complete silence about the nature of the project.  Blog + confidentiality = Instant ethics issues, methinks.

Second, if you’re working on a manuscript, presumably you’re going to have to keep everything you do quiet.  Heck, I’ve got a paper in the works for which the journal sent instructions that require absolute silence on whether it’s even been accepted or not, let alone contemplate communicating anything about the topic.  If I say any more about this, I’ll either jeopardize the publication or wind up in jail.  (Have I already said too much?)

Third, if you aren’t working on a manuscript, you’re either not an academic, or you’re working on an open science project.  I was fortunate enough that I my own project was open, allowing me to talk about my Chip-Seq work for the first three years of my PhD – but alas, that work never cumulated into a second paper.   That’s another rant for another day.

That leaves scientists in the awkward position that they either:

  1. blog about someone else’s work – as if they were journalists, describing their own fields,
  2. blog about their own work in vague terms so that their competition doesn’t scoop them,
  3. blog about work they’ve already published.
  4. blog about the unimportant stuff – or the stuff that they don’t plan to publish.

I can think of one exception: Rosie Redfield, who does a good job of writing about what she’s working on, although her recent work has all been about rehashing and verifying (or more accurately not being able to verify) someone else’s results.  (Yes, I’m referring to the arsenic bacteria fiasco.) I have to admit, I don’t follow any other bloggers who discuss their own data in public, but I’m sure there must be some out there…

Still, if this is a problem for academic bloggers, industrial bloggers face an even harder battle to discuss their own data.  I can think of Derek Lowe over at In The Pipeline as a great example of a blogger from industry.  I used to read his blog daily, and back when I was an avid reader, I seem to recall my favorite posts of his were from the lab – but were all about the strange mishaps and challenges faced by chemists, drawn mostly from the past.  Absolutely none of his current work was discussed, unless it ended in spectacular failure. (Those were good stories too…)

So, I often find myself wondering, when I hear people say that scientists should blog more about their own work, who exactly do they expect to follow that advice? (Btw, It’s something that pops up in conversation frequently, although I couldn’t think of a blog entry that makes that case specifically, off hand. If you need a citation, you’ll just have to settle for “personal correspondence.” Sorry.)

Are there a group of scientists who are willing to blog their own work at the expense of getting publications or being fired from their jobs?  Somehow, I have yet to meet this clique – although if I did, I’d have a lot of questions.  And I can’t imagine they’d be in a position to do this for very long.  You don’t get grants renewed without publications – and you wouldn’t have a workplace for very long either, if you kept blogging the secret sauce recipe.

Maybe, however, this is why some scientists chose to leave the lab bench to pick up the mantle of journalism.  Cue Ed Yong, for instance.  So, the solution isn’t that we need more scientists blogging about their own work, but that we need more scientists to leave science to blog about other people’s work…. or perhaps we should just ask them to stay in science and blog about other people’s work already.

Ahem.  Status quo wins again!

Letting the Cat out of the Bag.

It is finally official – I’ll be leaving Canada and going to Europe (Denmark) in December – joining the team at CLC bio in just over a month. You’ll have to excuse my holding off on letting everyone know.  Of course, things have been in the works for some time yet, but the last few pieces have only clicked into place this week.  And, of course, one doesn’t want to jump the gun by announcing these things before everything is in place.

Of course, this doesn’t mean I’ve finished my PhD yet.  There are a still a few more hurdles – my thesis has to go through my committee and the external examiner, and I still need to officially defend it – but it was looking like the soonest that could happen would be February, and with everything going on, my wife and I decided it would be better to just start the process of settling in to Denmark as soon as possible.

So, consequently, if you read my blog, you’ll probably hear a little bit more about some topics that are currently on my mind: learning Danish (lære Dansk), traveling, maybe some cultural collisions (Danish people don’t have closets?)  and possibly some photography, depending on how busy I am.  (Yes, now that I’m not actively writing my thesis for 6-8 hours a day, I seem to have more time.)

But don’t worry – in the next month, I still have a few things I want to blog about, and likely a few papers to review.  Even though I’m leaving Grad School, I’m not leaving science behind.

To be candid, I’m looking forward to starting up at CLC partly because of the job, which already sounds pretty awesome, and because of the people.  I’ve met some of the people I’ll be working with – albeit briefly – and I’m excited to have the chance to work with them.  I can honestly say that they one one of the nicest groups of people I’ve ever met.  Must be something in the water. (-;

Anyhow, to complete the circular nature of this post (like all good fugues, which is the way to write a good post, particularly if you’ve read Gödel, Escher Bach, if that’s not getting way to involved) I have one last point to clarify. As foreshadowed lightly by the title of this post, yes, my pets will be coming with me – and undoubtedly my cat will be thrilled to be let out of the bag once we’ve arrived in Denmark… so the moving process will be bookended, effectively, by letting cats (figurative and literal) out of their respective bags.

Ollie - My wife says we have the same nose.

Cause and Effect, MBA Style.

There’s some discussion going around about the value of an MBA degree – a topic I have an opinion on, although strictly speaking, my opinion on the topic really isn’t important here.  What is important is that those who believe that the top schools give you value for your money in MBA land have published an article on the topic.

MBA Pay: The $3.6 Million dollar degree

What is somewhat confusing to me is that the authors of the article assume that going to the best school is responsible for the high salary.   It may not be a bad assumption, really, but I don’t think it has been demonstrated.

First, the “best” schools are the ones that can be most selective about the students they accept – and have the highest bars to entry (cost, connections, etc) that any student who wants to attend has to pass.  Personally, I think that this really indicates that:

  1. You are selecting students who already have great networks
  2. You are selecting students who are already skilled in many of the positive attributes of good managers. (Great communicators, clear thinkers, etc)

Thus, it shouldn’t be a surprise that these students go on to command high salaries, and are able to get great jobs.   Simply attending an MBA program may add value in terms of fulfilling the qualifications required for some positions, but does it really matter where you go?  Do you learn different things at different schools?  Or is this simply a matter that the top X% of the students go to the best schools and then those individuals are the most highly sought after regardless because of the skills they bring in with them?

Anyhow, I wonder what would happen if the employers didn’t know the names of the schools, or if the salaries for the dropouts from each school were to be compared.

It looks great that the name of the degree gets you the top dollars, but I would love to see that demonstrated beyond a simple correlation.

New ideas

It’s 6:00am, with three hours before Copenhagenomics and I’m solidly awake.  Jet lag is annoying, at best, but it’s been a great week of travelling and visiting in Denmark.  The interesting thing for me has been how stimulating it has been as well – even before the conference has started.

Part of that has just been getting myself out of the thesis mindset.  I’ve gone from being focussed on wrapping up my project to thinking a little further out.  That is, what would I work on if I were not summarizing my past work for my thesis. It was a question put to me by a bioinformatician at CLC bio, and I like sore tooth, I just can’t stop playing with it.

Because of it, I’ve come up with some wonderful ideas.  I guess this, to me, is just reinforcing the idea that sabbaticals really do work.  Even if the break from writing is short, just breaking out of the artificial walls I’d built around myself to keep myself from getting distracted from my thesis and papers has been a productive change.  Interacting with new people has been a great catalyst.

I’m really looking forward to the conference this morning and the opportunity to interact with more people and spark even more new ideas, but now I’m also looking forward to going home and getting my thesis done.  I have things I want to do and all this writing is standing in the way.

Cancer as a network disease

A lot of my work these days is in trying to make sense of a set of cancer cell lines I’m working on, and it’s a hard project.  Every time I think I make some headway, I find myself running up against a brick wall – Mostly because I’m finding myself returning back to the same old worn out linear cancer signaling pathway models that biochemists like to toss about.

If anyone remembers the biochemical pathway chart you used to be able to buy at the university chem stores (I had one as a wall hanging all through undergrad), we tend to perceive biochemistry in linear terms.  One substrate is acted upon by one enzyme, which then is picked up by another enzyme, which acts on that substrate, ad nauseum.  This is the model by which the electron transport cycle works and the synthesis of most common metabolites.  It is the default model to which I find myself returning when I think about cellular functions.

Unfortunately, biology rarely picks a method because it’s convenient to the biologist.  Once you leave cellular respiration and metabolite synthesis and move on to signaling, nearly all of it, as far as I can tell, works along a network model.  Each signaling protein accepts multiple inputs and is likely able to signal to multiple other proteins, propagating signals in many directions.  My colleague referred to it as a “hairball diagram” this afternoon, which is pretty accurate.  It’s hard to know which connections do what and if you’ve even managed to include all of them into your diagram. (I wont even delve into the question of how many of the ones in the literature are real.)

To me, it rather feels like we’re entering into an era in which systems biology will be the overwhelming force for driving the deep insight.  Unfortunately, our knowledge of systems biology in the human cell is pretty poor – we have pathway diagrams which detail sub-systems, but they are next to imposible to link together. (I’ve spent a few days trying, but there are likely people better at this than I am.)

Thus, every time I use a pathway diagram, I find myself looking at the “choke points” in the diagram – the proteins through which everything seems to converge.  A few classic examples in cancer are AKT, p53, myc and the Mapk’s.  However, the more closely I look into these systems, the more I realize that these choke points are not really the focal points in cancer.  After all, if they were, we’d simply have to come up with drugs that target these particular proteins and voila – cancer would be cured.

Instead, it appears that cancers use much more subtle methods to effect changes on the cell.  Modifying a signaling receptor, which turns on a set of transcription factors that up-regulates proto-oncogenes and down-regulates cancer-supressors, in turn shifting the reception of signalling that reinforce this pathway…

I don’t know what the minimum number of changes required are, but if a virus can do it with only a few proteins (EBV uses no more than 3, for instance), then why should a cell require more than that to get started?

Of course, this is further complicated by the fact that in a network model there are even more ways to create that driving mutation.  Tweak a signaling protein here, a receptor there… in no time at all, you can drive the cell in to an oncogenic pattern.

However, there’s one saving grace that I can see:  Each type of cell expresses a different set of proteins, which affects the processes available to activate cancers.  For instance inherited mutations to RB generally cause cancers of the eye, inherited BRCA mutations generally cause cancers of the breast and certain translocations are associated with blood cancers.  Presumably this is because the internal programs of these cells are pre-disposed to disruption by these particular pathways, whereas other cell types are generally not susceptible because of a lack of expression of particular genes.

Unfortunately, the only way we’re going to make sense of these patterns is to assemble the interaction networks of the human cells in a tissue specific manner.  It won’t be enough to know where the SNVs are in a cell type, or even which proteins are on or off (although it is always handy to know that).  Instead, we will have to eventually map out the complete pathway – and then be capable of simulating how all of these interactions disrupt cellular processes in a cell-type specific manner.  We have a long way to go, yet.

Fortunately, I think tools for this are becoming available rapidly.  Articles like this one give me hope for the development of methods of exposing all sorts of fundamental relationships in situ.

Anyhow, I know where this is taking us.  Sometime in the next decade, there will need to be a massive bioinformatics project that incorporates all of the information above: Sequencing for variations, indels and structural variations, copy number variations and loss of heterozygosity, epigenetics to discover the binding sites of every single transcription factor, and one hell of a network to tie it all together. Oh, and that project will have to take all sorts of random bits of information into account, such as the theory that cancer is just a p53 aggregation disease (which, by the way, I’m really not convinced of anyhow, since many cancers do not have p53 mutations).  The big question for me is if this will all happen as one project, or if science will struggle through a whole lot of smaller projects.  (AKA, the human genome project big-science model vs. the organized chaos of the academic model.)  Wouldn’t that be fun to organize?

In the meantime, getting a handle on the big picture will remain a vague dream at best, and tend to think cancer will be a tough nut to crack.  Like my own work and, for the time being, will be limited to one pathway at a time.

That doesn’t mean there isn’t hope for a cure – I just mean that we’re at a pivotal time in cancer research.  We now know enough to know what we don’t know and we can start filling in the gaps. But, if we thought next gen sequencing was a deluge of data, the next round of cancer research is going to start to amaze even the physicists.

I think we’re finally ready to enter the realms of real big biology data, real systems biology and a sudden acceleration in our understanding of cancer.

As we say in Canada… “GAME ON!”