Happy Halloween! A whole month has gone by and I haven’t written a thing here on Gydle. It’s not the funk, thank goodness, that has passed. I’m back in the saddle, writing away. I had a very relaxing vacation and knitted a pair of mittens. I am now a mitten-knitter, something to which I have always aspired.

Today as I was driving, I caught a snippet of one of my favorite TED talks, the one in which Elizabeth Gilbert of “Eat, Pray, Love” fame talks about the nature of genius and the dark side of success. I quoted her talk a while ago in a post on Inspiration.

I took it as a sign.

The important thing about the creative process, she says, is showing up day after day. You have to do your part, and trust that whatever inspiration or creative genius or whatever you want to call it will come and visit you at some point. You have to make the choice to put yourself out there and create something. Continue reading


It takes a long time for this old bear to learn her lessons. For the past few months I’ve tried to feed this blog and translate and run and work on my novel and keep everything going smoothly in our household and keep up with interesting things on the internet. And everything is going fine except for the novel. Somehow, all those other things are just so much more immediate. So much easier to tick off the list over the course of a day. But when the day ends and I’ve not put in the time on my writing project, I’m somehow unsatisfied. Continue reading

Fold It!

As I stand in the Lausanne train station holding a sign saying “Marcel,” the volume of passengers from platform 8 dwindles from a steady flow to a trickle to a stop. He probably exited the other end of the platform. I stay put like you’re supposed to when you’re lost. He was the 20-something computer geek. I’d let him find me.

Sure enough, a few minutes later, he does. This amiable, t-shirt-clad student has come all the way from Zurich after his 8:00 class at ETH to show me how to play a protein folding game called FoldIt. The IT dude in my novel is a player, so I have to learn it, too.

In EPFL’s Rolex Learning Center a half hour later, we quickly download the game onto my Macbook, since his HP is bugging, and he logs into his account. A list of protein puzzles appears, with names like quick fix the loop puzzle, New Player Puzzle: Pollen Allergen Protein, Quick Flu Design Puzzle 3, Symmetric Foldon Puzzle 1. Underneath each puzzle is a brief description. Here’s one:

Foldon is a small, 27 residue domain from the C-terminus of a phage virus protein called fibritin. Your job is to fold 3 chains into a larger trimeric domain that includes foldon. You’ll be allowed to move foldon around as well, but you can only mutate the residues in the polyalanine extension. And remember, three-fold symmetry will be enforced! If you are new to Foldit, make sure you have completed Intro Puzzle 5-2, & 7-1 through 7-4. More details in the blog.

Holy crap, what am I getting into? I think. But Marcel dives right in and puts the flu design protein up on the screen. The backbone, he explains as he twists the protein around, is made of amino acids, arranged in macaroni-like helixes, flat sheets and sausagey loops. Poking out from it are key-like side chains, the blue ones hydrophilic, or water-loving, and orange ones hydrophobic.


He shows me how to zoom and twist the protein around, how to put purple rubber band-like things onto various arms of it and pull it together or stretch it apart, how to change a loop to a helix to a sheet, and how to freeze one bit and tweak another. Hydrogen bonds, which look like blue-and-white barbershop poles, like to form between sheets and along helixes, he explains, showing me how to line them up.

Angry red bombs appear when things get squashed too tightly together – clashes. Big, pulsing red blobs appear when there’s too much empty space – voids. You want to avoid those. We fiddle with the side chains, rotating the orange ones in and the blue ones out. He even shows me how to “mutate” them.

The whole time, he’s keeping one eye on the score that’s evolving in the upper part of the screen. He makes a move that results in a huge loss of points; our score plunges into the negative numbers, turns red, and lots of red bombs appear. “Quick! Put it back!” I panic.

“Hang on,” he laughs. He’s totally relaxed. “Now we’re going to wiggle and shake.” He clicks a button and the whole structure starts bouncing, complete with a ticking soundtrack in the background. I watch as the points move rapidly upwards out of the red, then gradually slow down, while still increasing. After a while, Marcel clicks the wiggle off. Our total is higher than it was before!  Then he clicks another button and all the side chains start rotating. Once again, the score ticks upwards. We sit back, satisfied.

The points represent energy, he explains. The native structure of the protein is going to be its lowest energy state. The higher the number of points, the lower the energy state. But like a ball on a golf course, you can get stuck in a local minimum and miss the hole you’re shooting for. “It’s like this building,” he says, looking at the undulating floor of the Learning Center. “A ball will roll down into a hole. But that doesn’t mean it’s the lowest hole around. It’s just the one it was nearest.” Sometimes you have to pull back quite a ways and shake things up to get the ball to roll into a deeper hole – a lower energy state.

When a protein is manufactured in the cell, it zips into this native shape in no time flat. The shape is critical to the protein’s function. Sometimes, if the environment isn’t right or there’s a problem with an accompanying protein, called a chaperone, the folding doesn’t go right. Misfolded proteins are implicated in a variety of diseases like mad cow, Alzheimer’s, Parkinson’s and cystic fibrosis.

Scientists would dearly like to be able to predict the structure of proteins, because then they could design drugs that could fix the misfolded ones, or disable the harmful ones in viruses or bacteria. With this kind of knowledge, perhaps some day new proteins could be engineered for gene therapy or other medical miracles.

Algorithms to predict structure chug along on huge servers or in distributed computing networks, like rosetta@home, which uses spare CPU on home computers to run its calculations, but they take forever because they have to brute force every conceivable possible convolution. There’s no guarantee the algorithm will find the lowest energy state, either, even after all that calculating. It’s a really complicated problem. FoldIt taps into something these algorithms cannot – human intuition and pattern-finding capabilities.

Marcel shows me the different puzzles available – they range in difficulty from easy structures put up for newbies like me to complex proteins involved in actual scientific research. There are only a few on at a time, each one with an open window of about a week, in which players work either on their own or in teams to get the highest possible points before it “closes.” You can “evolve” a protein, which means you work on a solution, and then share it with other people, who then add their bit to it, and so on. The protein’s structure then progresses as a joint effort. You have two rankings – “solo” and “team,” based on your results in each category. Marcel is a member of the Androids team.

He estimates that there are about 300 really active players, spread all over the world. The master solo player is a guy from Slovenia called Wudoo.  A woman in Texas with a couple of kids, jpilkington, is the “evolver queen,” he tells me in reverent tones. While we’re playing, she comes online and starts chatting with other players. I tell her my brain is exploding. “LOL,” she replies.

Rav3n_pl, a programmer who lives in Poland, is a master at writing “scripts” –recipes that apply long strings of commands to the protein, which can be run in the background for hours while you’re off doing something else. Marcel started the flu design puzzle that morning. He first did a few manual tweaks, and then ran one of Rav3n_pl’s genetic algorithm scripts while he took a shower and ate breakfast. “The manual stuff can only take you so far,” he explains. After that, you eke out points at a time by running scripts. (These recipes, BTW, are the subject of a recent article in PNAS.)

As we continue to work the protein, I see what he means. The score appears to be stuck. “The deeper you are in an energy hole, the harder it is to move something,” he says.  He opens the “cookbook” he has set up on the left hand side of the window and starts a script. We watch the protein jiggle and shake, the points fluctuating wildly as it starts, stops, reverts and starts another iteration.

Finding your way out of the hole is an art. There are a few people who are consistently among the top scorers, he tells me. “It’s not just luck. There’s something – either they have an intuitive feel for how the programming works, or they see patterns, or maybe they just have good computers and can run tons of scripts.”

Marcel has been away for a couple of weeks on military duty. Even so, his overall rank is 61. Wow, I say, you must play all the time!

“No, not more than an hour or two a day, max,” he assures me. “And a lot of that is just scripts running.” He admits, though, that when a deadline is approaching, he might put more time in with his team.

Well, sure, but you must also know a ton about molecular biology, in order to be able to rack up a ranking that high?

“Nope,” he says. “I just like getting the points. Sometimes you make a move, and you get a few points, and the protein just looks right, and it’s an amazing feeling.”

He also likes the social aspect of the game. “I’d never just play it offline,” he says. “I like chatting with my teammates. What should be the next step? What’s going on in their lives?” True. He is a chatty guy. He’s spending the entire afternoon with me, an uber-noob novelist, after all.

I figure he got into the game because he’s a chemistry student. “Not really,” he tells me. “At first, I looked into the seti@home thing, but then, really, who cares about aliens? I found rosetta@home, and that was cool, proteins are important, and it was there that I found out about FoldIt.”

Finally, we open the most recent puzzle on the site, something called a CASP roll, a “freestyle” protein with 197 amino acids that has to be folded from scratch. Sometime in February, the best FoldIt solutions will be compared with solutions cranked out by algorithms running on servers and with experimental data from x-ray crystallography and nuclear magnetic resonance imaging.

“Just look at that!” Marcel says as we contemplate the unfolded backbone stretching off into the screen. “197 amino acids! It’s huge!”

The CASPs are cutting edge science. A previous CASP puzzle solved by FoldIt gamers was published in Nature in September. Researchers had been struggling with an enzyme in a monkey version of the HIV virus. Despite the existence of several crystal forms of the protein, they were unable to solve its structure computationally, even though they’d been working on it for a decade. But if they could figure out its structure, they could engineer a way to disable it, thus hobbling the virus. They posed it as a FoldIt challenge, and within three weeks, two teams of FoldIt players (the Contenders and the Void Crushers) came up with multiple possibilities for its structure, enabling the scientists to further refine the game, which in turn led to the discovery of several molecular targets on the structure that can now be used to develop retroviral drugs.

As I drove Marcel back to the train station later that afternoon, I felt a little guilty. He’d spent his whole afternoon playing FoldIt with me, and his score hadn’t moved a whole lot. But then I remembered he had a two-hour train ride to Zurich, and a USB internet key.

I can do this

Wow. I just want to go on the record here to report that writing 2,000 words a day is really tough. Last night, I was explaining the idea to Marc at dinner.

So how much have you written today? he asked.

Well, technically, 118 words. On the blog, I said.

So your first day is going to be one of your days off?

I can’t start with a day off! So after dinner last night I managed to crank out about 1,000 words. I got all the way up to where my main character leaves the office to go have lunch with the IT guy. Then I just ran out of steam.

Today I spent the morning translating, then went for a run. After my own lunch, I tackled lunch with the IT guy. I cranked away for what seemed like endless hours – and now my total is just over 3,000 words. Six pages of single-spaced text. Tons of riveting dialog.

I am already 1,000 words behind!

Well, I’m not going to waste my valuable typing muscles whining about it here. I still have four hours left in the day, technically. I can do this.

On another note, the Wikileaks guy, Julian Assange, lost his appeal (did he ever have any appeal?) and will have to go back to Sweden to face sex crime allegations. (Maybe his lack of appeal is why the sex wasn’t consensual in the first place?) Why Wired Magazine is reporting on this is beyond me, but there you have it. Word has it that documents from the rape investigation have mysteriously been leaked onto the Web…

A novel idea

Halloween has come and gone, hardly noticed here in chocolate land. Yesterday, the schoolkids traipsed by my house at lunch wearing normal clothing. It was so sad. Nobody got to wear a costume to school. (The Swiss don’t celebrate any holidays or birthdays at school, to be fair. School is for learning, not for partying.) Last night, despite my brimming basket of specially-purchased candy (I made an extra trip) we only had one group ring the doorbell. I even had a candle-filled pumpkin on the windowsill to beckon them in.

Maybe I got a bad reputation for what I did last year, when the village kids came trick-or-treating on October 30.

Come back tomorrow night, I’d said, genuinely shocked when they showed up at the door. I didn’t have any candy! (I can’t buy it more than one day in advance or I eat it all.) Today is not Halloween! The date is not negotiable!

Or maybe they remembered the year before, when I’d tried to explain Halloween etiquette. You have to say “trick or treat,” I instructed. I waited until they complied. And when you leave, you’re supposed to say “happy Halloween!”

In any case, it appears they’ve learned to avoid the snarky American lady with the ceramic pumpkin in the windowsill.

Never mind. More candy for me. Now it’s November, and as soon as I’ve saved my health by unloading the excess candy on my former office mates over at EPFL, I’m going to get down to business.

I’ve done a rash thing. I’ve signed up for National Novel Writing Month (NaNoWriMo). Although the name is misleading (it’s not limited to Americans or US residents), I think the overall idea is good. You’re supposed to crank out a novel in a month. You “win” if you manage to write 50,000 words. Nobody judges your work and there are no literary prizes involved. I love winning.

How hard can it be? I figure at 1,000 words a day, it’ll take me  50 days — oops. November only has 30 days. Recalibrate.

Hey, at 2,000 words a day, I’ll get five days off!

I already crank out nearly that in translations and blog posts every month. And I’m planning to refuse work for the next 30 days and hijack my blog, at least for a couple of posts, for excerpts from the developing novel.

Here’s the premise: Twenty-something writer in university communications office (gee, I wonder where I got that idea?) interviews highly reputed scientist professor x who is studying hot topic with big medical implications. Postdoc comes in during interview, meets writer, there’s chemistry. They start dating, writer discovers by accident that there might be more going on in professor x’s lab than meets the eye, and postdoc is not who he claims to be. Writer’s geek friend in the IT department (who is secretly in love with her) helps her uncover the secret using sophisticated hacking techniques and unsophisticated sneaky spying maneuvers. Things quickly get really weird and scary for writer who nonetheless saves the day (and keeps her job).

I just counted all those words – that’s 118 towards today’s total!

What do you think? Would you like me to post a few excerpts as I go? I might eventually put up the whole shebang on another part of my publishing empire site. Leave me a comment and let me know what you think.

I’m going to need help coming up with names, because I’m really terrible at that. I’ll need a name for the main character, for professor x, for the head of the communications office, for the geek in the IT department, and for the evil postdoc. (He has to be Swiss, though, keep that in mind.) The setting is in the US. I’m just not comfortable with all the language issues that I’d have to deal with if I set it here in Switzerland. If I pick a name you suggest, I’ll send you a free copy once the book is published! Hopefully this NaNoWriMo will get my butt in gear so it won’t be a decade before that happens…

While we’re on the topic of writing, I found a really cool website the other day, called Nieman Storyboard. It’s “a project of the nieman foundation for the study of journalism at harvard” (no caps) that basically deconstructs really good writing to see why it works so well. You get twice the bang for your buck: first, you find out about some really fantastic writing, and second, you find out why it’s such good writing. I’m hoping some of it will rub off on me.

David Dobbs’  deconstruction of Michael Lewis’ Vanity Fair article about the Greek Financial crisis knocked my socks off. I learned more from Lewis’ article than from all the newspaper stories I’ve read up to this point. It’s just so much more interesting to read what he writes. If you’re curious about the European debt crisis, read the Vanity fair article. If you’re interested in writing, read Dobbs on why it’s so great.

That should keep you busy for a while! I do promise, however, to write a post on junk DNA soon. I have some interesting stuff to share. And update you on my barefoot running progress (or lack thereof). Man, there aren’t enough hours in a day, even with daylight savings’ time…

Image: Marwa Morgan


There’s someone in my head, but it’s not me.” – Pink Floyd

Where do ideas come from? How many of us wake up in the morning and say, Gee, I think I’m gonna to have myself a great idea today!

Not me.

In general, the harder I try to think up something original, the slower my brain goes until it ultimately screeches to a stop and I have to go play a game of Scramble or eat jelly bellies to get it going again. Continue reading