It has been a long time coming, but a good chunk of the work I did for my Ph.D. has finally hit the press in this week’s issue of the Journal of Neuroscience. It is satisfying to finally see my work published in a peer-reviewed journal.
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Abstract
The work for this paper began about 5 years ago when I was still at the University of Calgary. The first time we submitted the paper back in 2002, the reviewers wanted to see biochemical evidence in addition to the electrophysiology that I had already undertaken. Luckily, when I arrived at UBC after the lab had moved from Calgary, a talented post-doc with expertise in biochemistry by the name of Francisco Cayabyab joined the lab. He agreed to teach me biochemistry and contribute his own expertise to the project. The two of us became a synergistic data-producing team, and today’s paper is the first (of hopefully many) tangible results of our effort. I think it proves that success in science requires regular golf and steak-and-egg lunches.
What the paper is about (in plain english):
When the brain is deprived of oxygen, bad things happen. Toxic chemicals are released that kill neurons (brain cells) by stimulating them to death. However, the brain is not defenseless. It can protect itself by releasing agents that prevent the toxic chemicals from over-stimulating neurons. These agents are called neuroprotective agents.
One of the most important such neuroprotective agents in the nervous system is adenosine. Adenosine is a potent inhibitor of excitation, which is why it is so good at protecting neurons from over-stimulation. Adenosine prevents the release of chemicals from neurons. Normally these chemicals (neurotransmitters) are required for neurons to communicate. However these chemicals become toxic if present in excess amounts, which is what happens during a stroke.
Previously, it was not known how adenosine prevents the release of neurotransmitters. This paper shows that adenosine works by turning on a molecular switch (p38 mitogen-activated protein kinase), which then prevents neurotransmitters from being released. If the action of this protein could somehow be increased during oxygen deprivation (which occurs during a stroke, seizure, or head injury), it could prevent cells from dying. It is important to understand the steps by which adenosine (the brain’s natural defense against oxygen deprivation) decreases the release of neurotransmitters because it could eventually lead to a therapy that prevents brain damage caused by strokes.
On a more fundamental level, this paper increases our understanding of how the amount of neurotransmitter that is released from neuronal terminals can be regulated. This is important because changes in the amount of neurotransmitter released is responsible for many brain processes, including learning and memory.
Month: November 2006
Will the real Dr. Brust please stand up?
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On Wednesday November 22nd, sometime after 4:00 PM, I stood waiting to cross the stage at UBC’s Chan centre. I was wearing a blue and maroon (or maybe red or purple?) gown, long enough to trip over (and that fear did cross my mind). What had led me here? Where was I going with my life? I missed my undergraduate graduation ceremony because I was in Europe, and that I do not regret. It was now just over 10 years since the last graduation ceremony I had attended – high school.
I had given the valedictory address to my high school graduating class, as if I was somehow in a position to offer words of wisdom to my classmates. I would give a different speech today if I could go back in time. Instead of urging the class of 1996 to set lofty goals and work hard to achieve those goals, I would urge them to discover what made them happy and hold on to it. Life is too short to waste trying to achieve a version of ourselves that we think, or what we believe others think, we “should” be. I am now surrounded by people who are going to wake up one day and realize that their life has not turned out how they thought it should, and they will feel empty and demoralized. Despite achieving much of what they’ve always thought they wanted, they will realize that achieving goals does not equal happiness or contentment, only a brief satisfaction that must be repressed so as not to interfere with achieving the next “lofty” goal. I look back at my life and am grateful for the fun I’ve had, the friends I’ve made, and the time I’ve taken to enjoy myself. But did I really need to put so much effort into junior high social studies?
Ten years ago, I would never have guessed that one day I would be in medical school and about to receive my PhD, and yet still be unsure of what I wanted to do with my life. It seems strange that at the age of 28, I still don’t really know. My parents, self proclaimed hippies, proud of me as they are, still joke (half-seriously) that they wish I had pursued art or poetry or music instead of science and medicine. To this day, they proudly display my art from junior high and high school around the house. Surely they don’t miss the sound of my saxophone?
I thought back to a few days ago when I was at Toronto General Hospital to learn clinical skills. Wearing a stethoscope around my neck and an official hospital name tag, I had remarked to a friend while on my way to interview a patient: “I feel like I’m dressed up for Halloween.” He laughed and agreed.
In contrast, I realized that wearing that long blue and maroon or purple or red or whatever gown and over sized hat felt comfortable and completely natural. I “owned” that robe. I was awed by the gravity of the moment, glad that I had made the trip from Toronto to attend the graduation ceremony. I was happy that my parents, aunt, cousins (and Frank!) were in the audience. Maybe I could steal the robe to wear around the house? I had earned that right at least. The moment passed.
I had a piece of paper in my hand stating that the degree if Doctor of Philosophy had been conferred upon me. My name was read and I had my moment on the stage. I shook Chancellor McEachern’s hand, and he said “I admit you Dr. Brust”, thus signifying the official end of an odyssey spanning over six years to discover what “Ph.D.” actually stood for: Philosophiæ Doctor. But it turns out I had been asking the wrong question all along, and that the answer to the question I was supposed to have been asking is 42. Now I just have to figure out that question.
People have asked me if I plan on using my new title. Oh, how fun it would be to sign off all my emails “Dr. Brust”, or insist that my dad address me as Doctor from now on. Sadly, being a medical student is the one instance where I feel I can’t use my title. Because physicians stole the term “doctor” from the Philosophiæ Doctors a long time ago, it would be too confusing for the patients. They might think I’m a medical doctor and expect me to know what I’m doing, when in fact I have no idea…
I heart New York
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The SJC golf team was reunited in New York City this weekend. We stayed at Joel’s temporary accommodation (for which he is paying 112% too much) on the upper west side. Joel’s neighborhood is on the left hand side of central park (barely visible in the left middle background in the picture above). I took this picture from the observation deck of the Empire State Building. I’ve always loved tall buildings and I’m glad we went up to the top, despite the $16 charge, the lineups, and the security hassles. At one point I thought Joel was going to kicked out of the building, as he managed to have an altercation with a security guard at a walk-through metal detector (airport style). Joel was wearing pants with a lot of zippers. Anticipating the problems that the zippered pants might pose, Joel naturally assumed that the rent-a-cop would appreciate being told how to do his job. Unfortunately, this did not prove to be the case. Joel was told to either calm down or exit the building. It was a close decision, but Joel decided to stick it out and be a good sport.
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We crammed a lot into two nights and two days, including a meal at the Carnegie Deli, where we had encounters with not one, but two celebrities. Pictured on the left is the president and founder of the Siblings Day Foundation (the inventor of “Siblings Day”; to be celebrated on April 10th). Look for “Happy Sibling Day Cards” to come to a Hallmark store near you in time for the next Siblings Day.
The second celebrity encounter came when Andrew Dice Clay, accompanied by the flavour of the week (or maybe the evening?) sat down at a table across from us. Andrew Dice Clay has had a show in Las Vegas for many years.
When I saw Andrew Dice Clay, I was reminded of an incident that happened to a buddy of mine (Ryan) in the Monte Carlo poker room on one of our first trips (of many) to Las Vegas.
There was a woman at our table who was one of the worst poker players we had played against in our young poker careers. The game was seven-card stud (yes we’re so old that we started playing poker before the explosion of Texas hold’em). She was also one of the luckiest poker players that we had ever had the misfortune of playing against. Ryan and I had both been losing to her miraculous river cards. I gave up and went to play blackjack. Ryan stayed long enough for her to bust him out of his entire rack when he was “fortunate” enough to start out with rolled up trip fours (3 fours on his first three cards; the odds against getting trips rolled up are 424 to 1).
Of course Ryan went unimproved all the way to the river and Mrs. Lucky ended up catching a third Queen on the river to beat him. Normally her bad play would almost guarantee that she would spill her chips back. However, before Ryan had a chance to get his money back, Mrs. Lucky cashed out all her chips saying that she was going to go see Andrew Dice Clay. Ryan was left to try and earn his money back against a table of tight old ladies. It’s amazing how some poker hands are unforgettable.
The picture on the left shows the Tosser “enjoying” a completely dry burger. There were no condiments of any kind. It was a dry patty on a bun. I wonder if Tinkleberry was reliving his 15 hour voyage from the UK in his mind as he choked it down, asking himself if the whole thing was worth it.
When we paid our bill, after having Tommy do the math for us as usual, the waiter came and counted the cash at the table. He informed us that the tip was supposed to be double the tax. Having heard Tommy’s limey accent, he proceeded to instruct Tommy on the proper tipping procedure in America. Unlike back in England, waiters in America only earn $2.75 per hour and depend on tips to earn a living. The minimum acceptable tip is 15%. Of course we all knew that the Kid was well aware of this and had been deliberate in the amount he had left, which was just under 10% (he doesn’t make many mathematical mistakes). Still, the Kid feigned ignorance and succumbed to the waiter’s demand for a tip. I would have rather heard the Kid tell the astonishingly up-front waiter to “sod off” instead.
Unlike the dry burger, at least my mountain of pastrami had a covering of melted cheese an inch thick (below). I like cheese.
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We also squeezed in a whirlwind tour of lower Manhattan, where we saw the NYSE (above right), ground zero, canal street (I bought a ROLEX), and the craziest department store I’ve ever seen. It was packed full of people fighting for space to claw over, frankly, shitty merchandise. I couldn’t stand the place. This free-for-all shopping orgy, right across the street from the memorial for 9/11, is the definition of juxtaposition.
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One of the highlights of the trip for me was a visit to a Goth club (below) at about 3 AM on Saturday night. I’m glad we even made it there because both Tommy and Adam were crying, wanting to end the evening at the W hotel. Luckily the old men prevailed in convincing the children to stay up past their bedtimes. At the Goth club, I was so surprised to see everyone in costume that I think I lauged out loud. I found myself unexpectedly amused and entertained by the spectacle. The Kid, who looked ridiculous in the Goth club wearing his bright white pants and golf shirt, advised me to adopt the Goth look as I’m “already halfway there”. I was wearing black jeans and a black leather jacket. My shaved head works. I just need a little face paint, or maybe just some black eye-liner, and I’m good to go.
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Wilderness Medicine
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For some unknown reason, I ended up being the only guy that went on the Wilderness Medicine Retreat this past weekend. I didn’t mind at all.
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We spent Saturday hiking parts of the Bruce Trail (which is over 600 km long). It was tipping it down, so we ended up covered with mud. We spent Saturday night at Hart House farm (which is owned by the University of Toronto, pictured at the bottom). We made a big bonfire. There was a woodshed with a large axe for splitting logs. I chopped way more kindling than we needed to start the fire, but I was enjoying myself too much to stop. The girls couldn’t figure out why I was so keen on chopping wood. They chalked it up to a “guy thing”. Come one, who doesn’t like the feel of an axe in his (or her) hands?
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On Sunday morning, an emergency room doctor (Dr. Cheng, bottom left) with an interest in wilderness medicine kindly came out to Hart House farm to teach us some basic skills such as assessing the airway, breathing, and circulation (ABCs) on a victim with a possible cervical spine injury. We also learned how to “wrap” and evacuate an injured (and immobile) victim who was also suffering from hypothermia (above). In addition, we learned how to splint fractures of the ankle, leg, wrist, and forearm MacGyver style, as well as how to stabilize a neck fracture. We also learned ways to reduce a separated shoulder in the field. Finally we went through what to include in an expedition medical kit (always include safety pins!). It was a fun and informative weekend. Who knows when this training will come in handy.
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Long Way Round
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One day Ewan MacGregor (of Obi-Wan fame) was pouring over a map of the world and noticed that Russia and Alaska were actually quite close. It occurred to him that you could go almost all the way from London to New York by land the “long way round”. Ewan and his best mate Charlie Boorman had a passion for motorcycles, and the two of them hatched a plan to go around the world by motorbike. They pulled it off in the summer of 2004, going 20,000 miles from London to New York in 115 days riding BMW 1150 Adventures.
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Ewan and Charlie recorded their adventure in a book and a DVD set, both entitled “Long Way Round: Chasing Shadows Across the World”. I read the book in a couple of sittings (it was almost impossible to put down) shortly after returning from my maiden voyage on a motorcycle through southern California. I highly recommend it, even if you’ve never ridden a motorcycle and don’t intend to. Tonight I finished watching the DVD. Ewan and Charlie’s story is enough to make even the most unadventuresome person dream of embarking on a round the world (RTW) motorcycle adventure. Reading the book planted a seed. I decided that if I ever got the chance, I too would travel the world by motorbike.
The DVD shows spectacular scenery and the encounters they had with people living in the places they passed through. It’s hard to believe that a place like Mongolia actually exists on our planet. The DVD makes me want to go there, and leave tomorrow.
Tom and I have been discussing a possible round the world (RTW) trip by motorbike for some time now. However, the odds of us actually pulling off a “Long Way Round” adventure of our own are stacked high against us. I will be in intensive training for the next 9 years, accumulating debt, with basically no time off for any RTW foolishness. Tom has an actual job. How can he justify taking several months off to go RTW on a motorbike? We both want to do it, but the logistics are hard to overcome. I only have two summers off in the next decade: this summer (2007) and the summer of 2008.
A RTW trip takes 2-3 years to plan, and typically costs about $20,000 (not incuding bikes and equipment). Realistically, the only time we could go would be during the three months that I have off in the summer of 2008. Financially I can’t afford it, but I can live with that. I have no problem borrowing against my future earnings for a life-enriching experience like traveling around the world. If my credit runs out before I’m done medical school then I will deal with it then.
The RTW trip will also be tough to pull that off in terms of planning. I’m not sure a little over a year is enough time to plan the trip, or whether we can even make it around the world in only three months.
Tonight we started talking about possible routes for the RTW adventure. Talking about routes made the trip seem real to me. This wasn’t fantasy anymore. When Tom and I talk about things like this they have a tendency of happening. The golf/cowboy adventure of August 2005 and the golf/easy rider adventure of July 2006 are both examples. We can certainly make a RTW trip happen.
We are also planning a less ambitious, but still daunting, motorcycle adventure for this summer (2007), but we haven’t quite decided on where yet. A discussion of the much more ambitious RTW trip of 2008 came up when we were trying to decide where to go for the June 2007 trip. Our options for the June 2007 trip were 1) Eastern Europe + North Africa; 2) Central America; or 3) Argentina + Chile + Peru. At this point we both are leaning towards Argentina because we want to see the Andes and neither one of us has been to South America.
We wanted to go to a place this summer that wasn’t on our planned route for the 2008 RTW trip. Why go to the same place twice when there are so many places in the world that we would like to see and so little time to see them? This necessitated the discussion of routes for the RTW trip.
We managed to narrow the RTW route options down to a few choices. The difficulty of traveling by motorbike in China pretty much eliminates that country. Myanmar is not passable at the moment. The middle east is iffy. The border between Algeria and Morocco is closed. Thus, going RTW from west to east requires retracing Ewan and Charlie’s trip from the London to New York via Ukraine, Russia, Kazakhstan (I like), Mongolia, Siberia, Alaska, Canada, and the continental US. This route is marked in royal blue on the map below. It requires flying from Magadan in Eastern Siberia to Anchorage, Alaska. The road of bones in Siberia is not considered passable on a motorcycle by most standards. Ewan and Charlie did it, but they fought one swollen river crossing after another, and had to rely on loading their bikes on passing trucks.
Another option is to do the Great African Circle (marked in pink). This route starts in London, goes through France, crosses the Mediterranean between Italy and Tunisia, continues east to Egypt, and then cuts down the East coast of Africa, past the Horn, and down to the Cape. We would then make our way by boat from Cape Town up the west coast of Africa to Senegal. This would allow us to ride through the Moroccan Sahara, cross to Spain, and head back to London. Another version of this trip starts in Scandinavia (“The Long Way Down”).
The last option would be to do the Pan American highway from Alaska all the way to the tip of South America (marked in cyan).
There are pros and cons for each of the routes, but I will save that discussion for another time.
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Am I crazy to want to do this? Is it absurd to think that I can actually make it around the world on a motorbike? I am currently reading a book called “Jupiter’s Travels” by Ted Simon. Ted Simon quit his job for four years to travel the world by motorcycle in the 1970s, and “Jupiter’s Travels” is an account of that adventure (and was in fact an inspiration for Ewan and Charlie’s trip). In Jupiter’s Travels, Ted Simon writes that “many people dream about going on an epic adventure around the world, but so few actually do.” He says that most people feel trapped by their own lives and have convinced themselves that they “can’t” go. I hope I can keep the bars from closing in.
Why do I want to do this? I want to experience the world. I want to challenge myself. I’ve already proven I’m a sucker for punishment by doing a PhD and going to medical school. Why not add getting stuck in a Saharan sand dune or a Mongolian bog?
Halloween
Cliched mastercard commercial ripoff:
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Leather armoured biker jacket: $500
Full-faced Shark DOT Helmet: $300
Joe Rocket riding boots: $250
Riding gloves with fibreglass knuckle protection: $80
Leather chaps: $100
Skull T-shirt: $30
Giant skull belt buckle & belt: $25
Silver medallion with sword (plus chain): $15
Terminator 2 sunglasses: $10
Skull bandana: $5
Skull ring: $5…
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…Priceless
I love Halloween. It’s my favourite day of the year. This year I rode Helen to school. I showed up late for class in full motorcycle gear, chaps included. The lecture came to a stop as all eyes followed the mysterious biker as he swaggered all the way up the stairs to the back row. No one knew who it was until he removed his helmet.
Later on that night, I had fun terrorizing tricker-or-treaters. I rode my motorcycle on the sidewalk, revving the engine until it was screaming. I managed to scare the hell out of a bunch of kids. Ah, how I wish it could be Halloween every day.
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