The human machine: coding and decoding

The previous post in this series can be found here.

It's been an exciting week for molecular biologists, and should have been for everyone else too! This week, the Encyclopaedia of DNA Elements programme has revealed its first results about the role of the 99% of the human genome that has, until now, represented a fairly sizeable gap in our understanding of how DNA works. This has made big waves in biological circles and has to some extent penetrated the mainstream media, on the BBC for example, but I thought I'd herald this great work by giving you a brief explanation of what DNA is, how it works, and why so much of it was a bit of mystery until now.


From humble beginnings

DNA is unbelievably complex yet unbelievably simple at the same time. The principles upon which it is based are extremely simple: a string of code made up of four chemical units (called nucleotides: G, C, A and T) on two intertwined strands where units on opposite strands are paired either G:C or A:T. The complexity that arises from such a basic principle emerges much in the same way that vastly complicated computer programs can emerge from the binary 1 and 0 system of computer code; principally, that it is a code there to store information that, when read correctly, is vast. And when you have around 3 billion units of this code in every cell in your body, that vastness can quickly become unfathomable! 

Nonetheless, we've come a hell of a long way in the last 60 years. It was only in 1952 that the Hershey-Chase experiment conclusively demonstrated that DNA and not protein, as had also been suggested, was the information-carrier of the cell. Just a year later Watson, Crick, and Franklin discovered the now famous 'double-helix' structure of DNA, and the race was well and truly under way to decipher this mysterious molecule. 

Higgs: A view from the moment of discovery!

[Note from Shaun: When Mikko wrote us a guest post about the Higgs discovery he also gave me a short note he had written on the day CMS first opened their 2012 box and looked at the Higgs-relevant data. I decided to save that note for a rainy day. Today, is that rainy day (literally, in Helsinki). What follows is more or less exactly what Mikko wrote down the evening that he and about 100 other people first learned that they really had discovered an entirely new fundamental (probably) particle. The rest of us couldn't be there in that room, but we can read about it now!]

**** Do not open before July 9 *****

Recollections of a Higgs discovery

It's not official yet, and will not be for another three weeks, but you could say Higgs was finally discovered today, on Friday, 15th of June, 2012. More than fifty years of searching, and there it is, at 125 GeV, just like the first hints last December indicated.

The big occasion was the unblinding of the 2012 data set at a Higgs meeting held at CERN at 15:00 hours on Friday evening. The meeting venue, the non-descript Building 222 better known as the Filtration Plant, was stacked with CMS physicists, with half of the crowd sitting on the floor or leaning against the back wall. The air was dense from expectation, and immensely hot from the mass of people and failing ventilation.

Everybody was appropriately informed of the formal proceedings of the day: the slides would not be posted on the web, no recordings of the video meeting would be allowed (except an official one by the CMS Outreach Team), and nothing shall be leaked outside the collaboration after the meeting. Only the highest level of CMS management had seen all the results before, at a special preview held at 11am in the morning.

For the uninitiated, I should probably explain what the unblinding is all about. Scientists are intimately aware of unconcious biases in analysis, when the stakes are high and the statistics are low. Therefore, it is considered good practice to not look into the signal region before fixing the analysis procedure and cuts. The expected background in the signal region is estimated using side bands, and the analysis only proceeds to look in the signal region, the "box", when those side bands are found to be sufficiently well understood.

The Higgs group had agreed that nobody would look into the signal region of 2012 data before today (or yesterday evening really, to allow some time for analyzers to prepare their talks). The previous week was spent by review committees scrutinizing each of the analyses and making sure all the systematics were thought of and no obvious mistakes would remain. Only the analyses given official green light would be allowed to open the box, and the whole collaboration was invited to join the event.

A significant fraction of the three thousand collaborators apparently did indeed join, most of them remotely. From the first few minutes it was clear that the video meeting system was creaking and was barely holding the traffic. The outside world could hear the audio, and we could hear some of them (despite frequent reminders to mute), but the video feed was apparently stalling. With no slides posted, the people in the videoland were more or less blind.

All the more reason to feel privileged to be at CERN to listen to the talks in person.

The first three talks were strategically ordered to go from the channel with the worst mass resolution and lowest expected sensitivity to the one with best resolution and expected sensitivity. The HWW (Higgs decaying into two W bosons) analysis got the honor to be the first messenger.

After a bit of a jumpy start with switching lights on and off for better contrast on the video projector, trying to transmit slides outside CERN and accidentally dropping the network connection, the talk finally got up to speed. Several slides showing impressive agreement between data and simulation covered the sidebands before moving on to signal regions, with quite visible excesses. The bottom line: a little more than a three sigma excess with combined 2011(5/fb)+2012(3/fb) data, precisely in agreement with the standard model expectation for a 125 GeV Higgs. Hey, this starts to look quite promising!

After a few more minutes of more and less technical questions from the collaborators we turned to the Hgammagamma (Higgs decaying into two photons) channel. The talk was given by a young Chinese graduate student from MIT, who'd obviously absorbed the American style of putting a bit of drama into the talks. With skill she had the collaboration holding their breath waiting to see the new limit plots... with a gigantic peak and a local excess of more than 4 sigma at 125 GeV when combined with 2011 data.

At that point I had to fight a bit breaking into tears. Those two channels alone meant that we'd have to be above the 5 sigma discovery limit already. It would mean we had discovered the Higgs. After 50 years of searching. Us, here.

Ok, back to sobering up a bit. The signal was much stronger than expected from standard model, which means we had either got very lucky, or that this could be a non-standard-model Higgs. All the better, we might have more to discover later in the year. The measurements from different subcategories of photons pairs and from 2011 and 2012 looked all perfectly consistent so there was no hint of a measurement error.

The last of the big three talks was ZZ4l (Higgs decaying into two Z bosons, which in turn decay into four leptons). This is the ultimate channel with very little background so you could even claim with good probability that some individual events are from a Higgs boson decay, unlike in the background dominated HWW and Hgammagamma channels. The expectations were already high from the two previous talks, and the results certainly did not disappoint. Around half a dozen nicely clustered events right at 125 GeV, just like the standard model predicted.

It's interesting to note that improvements to the analysis, like Particle Flow based lepton isolation and recovery of photons radiated off the Z bosons, had both improved sensitivity and caused the secondary peak seen at 119 GeV in 2011 to disappear. The updated results combined with 2012 statistics made a very convincing case, racking up another 3 sigma or so.

The main trio was followed by a fourth talk on VH (Higgs produced in association with a vector boson, i.e. Z or W), which however had not yet been granted green light to open the box. Nevertheless, the analysts had made nice improvements to the analysis, gaining 50% more sensitivity out of the 2011 data, and showing a small excess consistent with standard model Higgs. A planned fifth talk on Higgs decaying into two tau leptons was postponed pending more checks, as was appropriate. The background checks before opening the box were clearly taken seriously.

Overall it was quite a tour-de-force, with all channels lining up in unison. This is still not all, because the analyses used only the first 3.9/fb of 2012 data collected until June 8, and in most cases even less. With 5.6/fb already in the can today and three more days to go to reach above 6/fb, the analyses will likely have about 50% more integrated luminosity for ICHEP. This might be enough to take some channels already above 5 sigma by themselves.

In the short summary the Higgs conveners reminded everybody that this is really a result by everybody in the collaboration, not just the Higgs group: thousands of people had contributed in building, maintaining and running the detectors, writing reconstruction software, calibrating the detectors, checking the data etc. The final analysis was only the tip of a large iceberg. And the work was not yet over, there was still plenty to do before presenting the results in Melbourne, Australia on July 9.

A final warning was given before people departed the room: smiles should be subdued and no champagne bottles should be popped in the cafeteria; there were filming crews outside that had not been allowed in the meeting room, and they had vowed to film the expressions on the people as they came out. We should not let the world know just yet ;)


At CERN in Geneva, Switzerland
June 15,

On the Road, vol. 2

Three six-week slots ago I was writing from Berlin in the midst of a long-ish research trip. I feel like I've been moving constantly ever since. When I left for Europe I'd just accepted a new job in another corner of the world, and that month on the road was partly spent getting used to the idea of a big transition.

Returning to Chicago in early May, I had 0% of the move organized. I hadn't even told a lot of people about it! By the middle of July I was entirely packed down (well, kinda...), my deconstructed apartment was on a truck somewhere in the Midwest, hurtling its way to the Pacific in the form of a boat docked off the coast of L.A. I was saying a lot of farewells.

Right now, I'm juggling a new role and the inevitable, mundane logistics of repatriation with the process of finishing my dissertation write-up. It's quite a balancing act, but it's also the kind of spatial and life transition that — varying the specifics — young researchers have to do almost routinely. Shaun (who very kindly helped me out six weeks ago, mid-move) has had his own intense post-PhD experience, and James will be finishing soon.

Realistically, I won't be able to be a ubiquitous presence on the blog in the months to come. But I'm fundamentally committed to the idea that it represents, so that rather than bowing out for a period I'd rather attempt to maintain a lighter presence here by posting snippets that might illuminate the transition from graduate school to professional life — which is a fundamental, even foundational aspect of academic life. Over the last months lots of people have empathized by telling me about their own post-PhD transition, whether it was undertaken 3 years or 3 decades ago. So I thought I'd use my own experience as a point of departure for a conversation and some fact-sharing about the joys and sorrows of academic and extra-academic nomadism.

In actual fact, I suspect that the juggling act of the coming months will be good for my work and writing in calling for a whole new level of discipline, and so intellectual and argumentative succinctness. But we'll see. Use the comments tool to ask me questions and I'll attempt to respond. And please, share the details about your own crazy move. 

Chicago, Illinois. June 2012.

Wellington, New Zealand. August 2012.

Pushing back the boundaries

The Red Planet?

The adventure of NASA's Mars Curiosity Rover took an exciting step forward today as the pioneering little machine vaporised its first rock with its cheerfully named 'ChemCam' laser. The Curiosity mission has tapped into a huge vein of public enthusiasm for investigation and the exploration of the unknown, exemplified by the fact that over a thousand people gathered in New York's Times Square to watch the live landing. Space exploration has often occupied a romantic place in the heart of public opinion, in part because of the wonderful images that can be beamed back, which can offer a more personal connection to the work being done and give people a greater sense of ownership over scientific endeavour. The Curiosity mission is no exception - NASA is dutifully publishing the images being sent back from Mars to the delight of those of us on Earth.

The potential for images to capture the public imagination has not gone unnoticed by other branches of science. Last year I published a post about the Cell Picture Show, a project by the biology journal Cell to highlight the most striking images emerging from the ever expanding field of biological microscopy. In this post I wanted to highlight a recent edition to the project: the super-resolution gallery.

Super-resoltion is a fairly recent step forward in microscopy that allows biologists to observe life's molecular events on an unprecedentedly small scale using a range of cunning technical tricks. Researchers can now follow individual molecules as they move across the surface of a cell, or observe the machinery of processes like DNA replication in fine detail. Just like Curiosity, the missions of super-resolution are pushing back the frontiers of knowledge and exploring the unknown; not going further, but looking smaller. I would definitely recommend giving this new gallery a look: here.  

Image is property of Cell and National Institute of Health - microtubules imaged by conventional (right) and super-resolution (left) microscopy within a Drosophila cell.

Faster, higher, stronger... bigger and earlier!

The Olympic Spirit 

Let me be honest, as I write this I am heavily distracted by highlights (and now the closing ceremony) of the Olympics and as such this post won't be quite as substantial as I'd originally intended. If you're not a fan of the Olympics, then you've either never tried to be a fan of the Olympics, or you have no empathy. The point of the Olympics is not that being faster, higher or stronger actually matters, because it doesn't. Of course it doesn't. Nothing changes because of who won what in which event. The point of the Olympics is that despite the overwhelming and terrifying arbitrariness of human existence a group of people have decided to passionately care about something.

The worst sin in life is not to live. Nobody can claim that any Olympian is not living. The passion (and the story) of each and every competitor, is why the Olympics is so enjoyable to watch. And, given the arbitrariness of life, why not passionately strive to be faster, higher or stronger?

But, if faster, higher or stronger isn't for you, pick your own mountains to climb and climb them instead. Then, while you climb, share your journey with the world. And enjoy it when, as has been the case for the last two weeks, the rest of the world shares their journeys with you.

Just make sure you're climbing something!

The Spirit of Exploration 

The mountains those of us at this blog are climbing (most of the time) are the Twin Peaks of discovery and understanding. Rather than jumping a little higher or running a little faster we hope to see a little further. Our goal is to explore the unknown wildernesses of existence.

A look at science from another side of the trench

[Note from Shaun: The following is a guest post from Claudia Mignone. As you will learn from the post, Claudia is a scientist turned science writer and she shares below her thoughts on the divide between scientists and science journalism. Her past lives on both sides of this divide allow her to also see both perspectives of a world that can sometimes descend into acrimony. Enjoy... (all credit/blame for the image captions is my own to bear)]

Heidelberg! A university here sometimes awards PhD's to starving cosmologists.  (Photo by Claudia)

I am an astronomer/cosmologist by training, and have been happily working as a science writer for almost three years now. In this post, I will explore the borderline that divides the people in the “trenches”, who are actively conducting research and producing scientific knowledge and results (what we like to call the “scientific community”, whatever the term really means), and everyone else who has an interest in the outcome of such research (let's call them “the public”). The borderline is quite an interesting grey area. Its width may vary significantly and continuously on the basis of a large number of factors and it remains partly unexplored by many. As someone who has spent some time working on both sides of this blurred region, I thought I'd share some thoughts that might be useful, particularly to the folks who are still locked in the “trenches”.

Before I start doing so though, let me just add some sort of disclaimer: I don't mean to dispense any sort of “wisdom” here. All of my thoughts and observations are based on my own personal experience (plus that of many colleagues/fellow scientists that I've encountered along the way) but are by no means of a general nature. It is very well possible that others have gone through quite different paths and might disagree with the view that I developed along mine. I haven't conducted any study (neither thorough or superficial) on any of the subjects I'll mention – although I'd love to do so in the future! – so I won't draw any conclusions, because I haven't reached any – yet. But maybe I'll try to propose some advice here and there. Feel free to take them. Or not.

One year in The Trenches...

The five year extrapolation

Today is The Trenches of Discovery's first birthday. It's been a pretty cool year. It hasn't exceeded my wildest expectations, but it has exceeded my worst fears. We're chugging along nicely, with growth figures that, so far, match a pretty regular exponential growth. At the moment our viewing figures are still relatively humble, but if they keep following this exponential curve then, in about five years, the entire world will be checking out The Trenches of Discovery every day (I just made that up, I can't be bothered working it out in detail – but it's close enough). After that, I guess the governments of the world will have to organise successive baby-booms to keep our viewing stats rising.

Tell us about yourself

I thought, to mark the occasion, I would do two things. Firstly, I'll do something I've seen some other blogs do, which is to ask you, the reader, to tell us about yourself in the comments. What's your background? Where are you from? How did you find this place? What sort of posts of ours do you like? What is your favourite colour? What is your quest? What is the air-speed velocity of an unladen swallow? The usual. I'd love to know who the dudes out there are that are reading what we write. The comments are still completely unrestricted, so you can post as anonymously as you wish. Feel free to ask us questions in the comments too.

Trench Points

The second thing I want to do is have a small competition. I will give 20 Trench Points to the first commenter who correctly guesses what our most viewed post is. Everyone else who correctly guesses will get 5 Trench Points and as a consolation I'll give 1 Trench Point to anyone who's guess is one of our five most viewed posts. Then, for a super-bonus, if people want to guess how many views the most viewed post has I will give another 20 Trench Points to the closest guess. I'll announce the results this time next week.

What are Trench Points?

In case you're wondering I don't know what Trench Points are either. But, I'm sure that in five years time when we rule the world, they'll matter, so you better start collecting them now. More realistically, I guess, when we sell out and get merchandise they'll be able to be exchanged for free Trench Goodness. Clearly, this will only be true for people who don't post anonymously and use some sort of registered account. In the meantime, while we don't rule the internet, or have Goodness to give away, Trench Points will have to just be about inner feelings of awesomeness and achievement in life, as well as, of course, bragging rights with all your friends.

For anyone who does post with some sort of registered account (i.e. gmail address, Wordpress account, etc), I will keep a record of accumulated Trench Points over time and put them in a table somewhere.

Well, what are you waiting for, tell us about yourself...