Running, Two Acts

Act I

Of the many things I enjoy about Cambridge, the running routes are not among them. Narrow streets, congested sidewalks and miles of cobblestone make the city a runner’s nightmare. Nevertheless, I persevere for the sake of my addiction, and have found two main suitable running areas. When I’m working at the hospital, I usually take a mid-afternoon trot around the compound. Addenbrooke’s is a huge place; the hospital wards, research institutes, administrative offices, and outpatient clinics make it worthy of its own postal code (which it does have, btw). Consequently, it provides several interesting routes.

I love to run in front of the entrance to the main ward. With patients and staff milling around in front of the double revolving doors, I feel like I’m in a race, with spectators cheering and chanting my name, Boston marathon style. Of course, I am sure their most prevalent thought goes something like, “Crazy bloke, prancing around like a Newmarket pony in this weather. What a wanker” and then they manage that subtly disdainful/reprimanding eye-contact-avoidance that only the English can properly execute. But I do make the most of my imaginary fans by hurdling the low fences, weaving in and out of the stalled traffic, and giving heart attacks to old men by narrowly avoiding their walkers. While running I must look either miserable or exuberant, because I get tons of smiles that could be either sympathy or reciprocated joy. No way to tell with these people. I sprint the last quarter mile past the food court, and end at the front of my Institute: tired, aching, out of breath, and feeling so damn good. Fellow runners, you know what I’m talkin’ 'bout.

On the weekends or in the evenings when I don’t get the chance to run at work, I usually go into the city centre for some pedestrian-chasing. I live on Mill Road, which runs roughly east-west and intersects the northern border of the center of town. On the northeast corner of the centre, there is a huge green space called Parker’s Piece, which hosts pickup football (soccer), rugby, and field hockey games. Recently, it also gave birth to massive rickshaw skating rink, which will swiftly melt into oblivion after New Year’s. To get to town, I run west on Mill Road, turn southwest through Parker’s Piece, and into the heart of Cambridge.

On my third day here, I passed a man who could’ve been either crazy homeless or a slightly senile professor (once again, no way to tell) mumbling something about the pedestrian congestion in Cambridge. Despite his obvious mental deficit, he was clearly correct. It gets super crowded, especially on weekends and around 7 PM on working days. The novice runner’s nerve might fail at this gapless mass of people, but not me, friends.

I play a game of what I lovingly call “Avoid the Nervous Brit”. In the heart of the city, the roads are closed to motor traffic, so people crowd the streets and the sidewalks.

I weave. And let me tell you, faithful reader: I weave very well.

A foot of space opens between a bespectacled, tweed-cloaked man and a hippie whose long, dread-locked hair is intent on depositing its grease on my face. SHWOOP!! I dart through without a millisecond to spare!! Before the old man can mutter about young people and before the hippie can offer me dope, I’m on to the next obstacle.

Six teenage girls are 15 feet in front of me; a two foot space between them and the wall on the right. A male cyclist in hardcore cycling gear approaches about 50 feet in front of me, intent on making that space his bitch. It’s a veritable game of chicken, and neither one of us is about to back down.

He looks up at me, shades gleaming with the sunlight that has just appeared. His feet pump the petals twice.

I stare back, mouth open and probably drooling. I lengthen my stride.

15 feet, we both speed up. 10 feet, no one slowing down. 5 feet, his mouth tightens in fear and he braces for what he thinks is an inevitable collision. I chuckle softly to myself: rookie.

SHWOOP!!!!

One nanosecond slower and we would both surely have perished!!! His handlebars pass through the space between my tricept and ribcage. It’s so close that I can feel the plastic tickle my nylon shirt.

The girls, now behind me, don’t even notice the moment of daring bravery. I glance backwards and so does the cyclist. His head gives a nearly imperceptible nod of respect. I acknowledge it by oh-so-slightly lifting my chin. The girls continue to chirp.

A young mother with a stroller bares her teeth as I appear to threaten her infant with my jog. No worries, I assure her with a smile, and - SHWOOP!! - calmly hurdle the carriage.

SHWOOP!!- Side-step between two walking college kids. SHWOOP!!- Slide over the hood of a idling Mercedes (the driver is too stunned to honk). SHWOOP!! duck under the left side mirror of a speeding city bus. For the Cambridge runner, the joy and the danger go hand in hand.

Act II

I love to run, but telling people why is the problem. How do you describe the appeal of such a masochistic activity? It is 5-6 miles of discomfort, in weather that is often barely bearable, and completely without any sort of redeeming teleology. My body aches and my lungs burn. 20 years from now, I probably won't be able to walk because my knees will be completely broken.

It is truly an addiction, with all the accompanying side effects, including withdrawal. Three or four days without a run and I get anxious and irritable, hyperactive but lazy. Is it worth it?

...

Have you ever felt elevated above the mundanity of normal-ness? Where excitement, adventure, happiness, all the possibilities of life seem not just accessible but easily so?

When I run, those feelings swell within me like a song's gradual crescendo. Each step I take is another instrument joining the verse; I can feel chorus lifting me, and I soar, miles above the pavement with Adidas wings.

It's a song without words, rhythm, tempo, or melody, but I can hear it nonetheless. It emanates from everything, as if God himself was urging me onward. The little stresses and anxieties of the day become ethereal; ghosts without any power to worry me. But this isn't anesthesia; while my sorrows fade, the joys become brighter and more coherent. The music reminds me how funny that joke was, and how that girl's smile draws my eyes from across hallways.

Though I run towards nowhere in particular, I approach something. The air shimmers, parts, and through it the music shows me past, present, and future happiness. I see all my triumphs and my delights coalesce and join the music, become the music.

I am laughing aloud with jubilation and exhalation and I see the music spreading to everything my eyes touch. I run faster. I thank the music and it your-welcomes me with slight modulations in its toneless tone.

I lied before. My lungs don't burn, they hum with power, an electric generator in my chest. My knees don't hurt. How could they, when I'm running through air? The smiles I get are from the people who hear, just for a second, their own music through me.

...

The sun goes back behind the clouds (did it ever really emerge?). The air becomes opaque again (?)

I am drenched in sweat, chilled to the bone, with knees that will not survive the next 20 years.

But the music, though slowed and steadied, pulses lightly. In the wind I hear its non-existent melody, and in my friend's laugh I feel it's beat-less rhythm. "Come find me," it says- song without words-. "I'll be waiting."

SCIENCE!!!!! YA-AH!!

WARING: THE FOLLOWING CONTAINS HIGH DOSES OF SCIENCE. THE PHYSIOLOGICAL EFFECTS OF SCIENCE VARY WIDELY AMONG INDIVIDUALS, BUT CAN INCLUDE DIZZINESS, NAUSEA, OR INTENSE EUPHORIA. IMBIBE WITH CAUTION.

Cambridge has a long and distinguished history in natural science research. Charles Darwin formulated his theory of natural selection here. Watson and Crick solved the DNA code here. Researchers from Trinity College won the first thirteen Nobel prizes in medicine. Thirteen!!! That’s more than most countries have. With its illustrious history, it seems natural that an emphasis on scientific research would be placed in this city. Sometimes I think every other person I meet is a biochemist. It almost seems like research institutions outnumber restaurants (but certainly not pubs, the pubs nearly outnumber people.). Besides the University departments, there is the Medical Research Council’s Laboratory in Molecular Biology (home of several current Nobel laureates), the Hutchison Research Institute, and the Wellcome Trust for Cancer Research. As if that weren’t crazy enough, those places I’ve listed are only the ones based at Addenbrooke’s Hostpital!!!

I may be a little biased, but my favorite is the Cambridge Research Institute (CRI), which is the fourth national laboratory of Cancer Research UK, the world’s largest cancer charity. CRI is three years old, the queen herself cut the last construction tape in 2006. It houses 19 research groups with over 200 scientists and graduate students. The work conducted here is exclusively cancer research, and ranges from basic molecular gene expression investigations to pre-clinical studies in developing new cancer therapy drugs. It is truly a world-class facility. Articles in Nature and Science (two of the top scientific journals) are routinely published here. The equipment, facilities, and technical expertise unparalleled; nearly anything a biologist could want is available here.

The work being done here is serious. (Okay, kids prepare for some science jargon) Two months ago, one research group published a paper in Science detailing a drastically new approach to treating pancreatic cancer. The group had previously constructed a genetically modified mouse model which contained mutations in K-ras and p53 with restricted expression to pancreatic ductal epithelial cells. Unlike previous mouse models, the pancreatic neoplasia which resulted from these mutations recapitulated the pathophysiology of human pancreatic cancer almost perfectly. Using this mouse model, the group showed how most pancreatic tumors are characterized by very inefficient vasculature, which inhibits the delivery of chemotherapeutic drugs. They hypothesized that vascular efficiency could be improved by reducing the mass of stromal tissue surrounding the tumor. Using an inhibitor of the sonic hedgehog signal transduction pathway (Yes, that is the real name for it; the discoverers must have had a sense of humor), the group was able to decrease the volume of surrounding stromal tissue, increase tumor blood flow, and deliver conventional chemotherapeutic agents more efficiently. The results: 65% of mice showed a significant response to chemotherapy, and had survival rates of above 50% after 6 months, which is a really long time for a mouse. To give a comparison, the human 5-year survival rate of a pancreatic cancer diagnosis is less than 5%.

(More jargon) I work in the lab of Dr. Doug Winton, who is well known for his seminal work on developing the Cre-Lox system of genetic recombination. The Winton lab studies the development and differentiation of intestinal stem cells, and how aberrant stem cell behaviour can lead to colorectal carcinogenesis. My project involves analyzing stem cell differentiation by using a super cool cell line, called HRA-19. HRA-19 cells were derived from a primary rectal adenocarcinoma, and have the unique ability to differentiate in vitro into three different colon cell types . I am using this system to investigate how the timing of the replication of certain developmental genes correlates with differentiation status (For example, in stem cells some genes replicate early during S-phase, and when the cell differentiates, these same genes switch to late-replicating). I want to understand how these changes in replication timing are associated with the expression of these genes, and whether the changes in replication timing induce differentiation or are a side-product of the differentiation process. (I’ve got some vague ideas of how I might do this, but they probably won’t work. C’est la science).

IF, (and it’s a big if) changes in replication timing are a prerequisite for a differentiated phenotype, this could provide an interesting strategy for analyzing the epigenetic basis for differentiation. Why is this important? Many tumors show dysplasia, which is basically when cells turn into something they’re not supposed to. For instance, colon tumors may have stomach-looking cells in them, and breast cancer tumors have been shown to contain cells which produce enamel (teeth cells). This abnormal differentiation phenotype usually correlates with increased malignancy, metastasis, and a generally sucky prognosis for the patient. Finding new molecular pathways in this process could present new targets for drug therapy.

There are a lot of mights and maybes. My mentor at UPenn once told me that out of every 100 research ideas, 80 are crap, 10 just won’t work, 9 get published, and only 1 really makes a difference. Though I seriously doubt my project will culminate in a revolutionary scientific breakthrough, maybe I’ll get a journal article out of it!!

Speaking of publishing, I just found out that I’m going to be an author from my intersnship at UPenn several years ago! “Disabling the mitotic spindle and tumor growth by targeting a cavity-induced allosteric site of Survivin” is being reviewed in the Journal of Clinical Investigation. I can’t wait to PubMed myself (God that sounds egocentric).

Next up, more about my neighborhood, English dancing, and the British version of beer pong. Stay tuned.

Clouds and Cambridge, Good morning Britain

The goodbyes were long and heartfelt, the hugs were painfully firm, and my last two nights in Lawrence were filled with revelry, debauchery, and nose-breaking (sorry, Schnack). I awoke on Sunday morning with far too little sleep, and finished packing my last few things in my car. Two long hugs later, I was on my way to Kansas City. Shortly after that, I was at the airport, in the terminal, on the plane, and flying.

Stop in Chicago, have a piece of greasy pizza in the airport. Waste time on facebook and chat with a lovely girl from San Francisco. The intercom squawks and speedy British words assault my ears: “LadiesandGentleman wearenow ready tobegin boarding Unitedflight 205 toLondon…”

I glance out the window just in time to see the East coast…. Goodbye America.

Fitful sleep, even with Benadryl. Bad movies and decent chicken permit me some shut-eye, but not nearly as much as I hoped for. The sun rose and Ireland stretched before my wings. I’d always heard descriptions of the Emerald Isle’s lush hue, but to me it looked like just another land mass. Lovely, to be sure, but no greener than any other place with trees, rivers, and grass.

When we touched down, my foot rebelled against the rest of my body in a wave of tingly that always makes me want to surgically remove it for just a second. Also, I’ve never figured out why people are so damn anxious to get their luggage before everyone else. We’d been in the air for 8 hours, surely the guy next to me could wait 20 more seconds before barging across the aisle, shoving his pot-belly in my face and grunting while nearly concussing the short woman next to him with a massive carry-on. Pardon my unpleasantness; I was a little grumpy.

Heathrow Airport is an immense structure that has more white and yellow color than any other building I’ve been in. Mustard-colored signs helpfully point the “way out”, “toilets”, and “luggage carriage” for all eyes to see. My entire material life is in two large suitcases and a backpack. What a strange thought.

We’d touched down at about 7AM local time, and I had a busy day ahead of me. I was to take a coach (bus=intracity travel, coach=intercity excursions) to Cambridge, check in at King’s College, retrieve my keys, find my house, drop everything off, figure out the bus system, and take one to meet my lab and start the process of being a graduate student.

The coach dropped me off at a large park in the middle of town, and I started walking…

….and promptly looked the wrong way while crossing the street, nearly ending my education before ever starting. The driver of would-be killer compact car yelled something that may have vaguely resembled “Prick!!!!”, but there was really no way to tell. It could have been anything from “Pretzel!!!” to “Creek!!” Seriously, no way to tell.

In population, Cambridge is about the same size as Lawrence, KS, but has a much larger center of the city. I guess the founders didn’t have the foresight to structure their roads with any kind of coherency (damn those Dark Ages), because the winding paths, narrow sidewalks, and incomprehensible directional signs baffled me. Despite the peril, I managed to make it to King’s.

The College system at Cambridge is quite unique. When the university was founded in 12 hundred something, it was made up of autonomous organizations that were trying to escape the banality, hostility, and general unpleasantness of Oxford (which I can assure you still persists to this day ☺). Each college had its own criteria for student education, it’s own living and dining facilities, and its own staff and faculty. The “University” was just a reference to the physical proximity of these institutions.

As time progressed, the infrastructural requirements of scientific research forced the colleges to collaborate, and eventually this gave birth to the modern “University of Cambridge”. Courses here are jointly administered by the University and the colleges, usually with large lectures done through the Uni, and small discussions done within the college structure. It’s kind of a mess, but the English are very protective of their traditions (and rightfully so) so they hesitate to streamline anything. It’s all very charming, really. The colleges usually have about 400-1000 students each.

King’s college is one of the oldest, largest, and most prestigious of the colleges. My basis for picking it was its cool-looking chapel and a history of radical politics, according to Wikipedia. Walking down the narrow Benet St., I passed the famous Eagle pub (which I will be detailing in a later post) and turned the corner onto King’s Parade.

Whoa.



Heaven’s own light seemed to shine down on the entry gate, which I faced, and the Chapel just to its right. Tall, tan, and beautiful, the place nearly gleamed with history and regal power. Included among its alumni were John Meynard Keynes (second most famous economist behind Adam Smith), Alan Turing (the most brilliant scientist no one’s ever heard of), Salman Rushdie (award-winning writer), and Robert Walpole (first Prime Minister of Great Britain).

Brown stone and marble statues exquisitely complemented the green grass of the courtyard. I walked through the entrance arch to (one of) my academic home(s). The porters were pleasant, gave me my keys, called me a taxi, and wished me a good morning. Think Alfred the Butler from the Batman movies and you’ll have a pretty good idea of how these guys were.

I wanted to stay and gaze, but duty called. I stepped in the taxi and told the driver “Romsey Terrace”. He had no clue where it was. 2 minutes of discussion later, he finally figured out where I wanted to go, and left King’s behind us.

I live in a flat (British for apartment: usually multi-storied and narrow) with two girls: Bridget and Chloe. Bridget is Australian and Chloe is English/French, and they have both been incredibly nice to me. I’ve been offered food and wine many many times, which of course made them my immediate best friends. My room is about half the size of a closet, but it’s got a good view of the courtyard and a comfy bed.

The location is incredible. Romsey Terrace (my home street) is just off of Mill Road, which is filled with diverse restaurants, supermarkets, and weird stores (one acupuncture clinic claims to cure anxiety, depression, syphilis, yes that’s right, syphilis, and irritable bowel syndrome, among others). The thoroughfare is a lively place with late-night kebab shops, plentiful pubs, and tons and tons of cyclists. I didn’t know this when I arrived, of course. Having a place to put my bags down was good enough for the moment.

After a two-minute catnap (which was probably closer to an hour) I forced myself up and stepped outside, ready to meet the place where cancer and I were to battle. En Garde!!!!!!!

Next up: sciency stuff and pretty pictures

Hello, Hello

What a week!! Between moments of death-defying road crossing, getting lost for hours at a time, staring open-jawed at the outside of a 600-year old working chapel while nearly getting run over by a Vespa, I haven’t had time to breathe, much less write a blog.

But here I am, sitting in a room with a functioning fireplace, old desk lamps, and ancient tomes labeled “Close Rolls, Henry III, 1234-1238”. The dust here is probably older than my grandparents, and just as interesting-smelling. A chandelier hangs 10 feet in front of me. I sit, listening to heavy metal booming from the downstairs bar, and think of how I got here.

Many of you might have already heard my account of the problems I had with immigration, but the craziness really start right after I received the final clearance Her Majesty’s (HM) Government, allowing me to officially apply for entry clearance. I boarded a bus to Chicago on Wednesday night and arrived early Thursday morning.

My appointment at 9:30 was in the Wrigley Building on Michigan Avenue, about 2 miles away from the bus stop, so I decided to walk, as dawn revealed the Windy City to me.

In truth, I was so tired I can barely remember the trek. The bus was one of these pseudo-Greyhounds with high, rigid, polyester seats with veritable pits between them, preventing any sort of horizontal sleeping position. Walking through downtown Chicago, I vividly recalled how I hated watching the sun rise without having slept through the night.

As the light deepened and spread, a sense of irreality spread through my sleep-deprived mind, that I was moving so quickly through distance and life transitions after having been sedentary for weeks.

My experience with the British consulate was short and pleasant. Escorted by a security guard, the elevator took me to the 13th floor (whoaaaaaa) and dropped me in a small room with 3 chairs and a glass window. A plump, pleasant-faced woman smiled and said “ello”, scanned my fingerprints, captured my photo, took my documents, and assured me I could pick up my visa the next morning. The whole process took maybe 10 minutes. Ah, relief.

I was staying with my friend Megan, who didn’t get off work until 6, so I spent my day wandering Michigan Avenue, and eventually went into a Border’s. I found a big James Patterson book, opened it halfway, laid it on my chest, and napped.

An hour or two later, a particularly violent snore escaped my face and jerked me into consciousness. I must’ve been an amusing sight, because I’d attracted a crowd of not-so-subtle onlookers. Contacts swiveling, mouth dry, I rose and took my leave, not quite brave enough to give my admirers a bow and flourish.

The rest of Chicago was smooth smailing. The couch and the company were awesome (yay to Megan!!!) I picked up my visa (a shiny little sticker in my passport) Friday morning, and briefly contemplated getting back on that damn bus for another 11 hour ride. Southwest Airlines seemed to have sensed my trepidation: two hours and a last-minute discount fare later, I was on a plane to Kansas City.

(the exciting narrative continues on another episode of “Thornton Conquers Britain”)

P.S. Any savvy I might have had with electronic devices (which was little) was mightily defeated by a dearth of English power adaports. I.e. no pictures yet, but they’ll be up once I call in the cavalry.

Cheers!!!!