10:52 p.m.
There aren’t any cheering crowds – just the fluorescent glow of the ice and the thrum of the Zamboni as captain Michael Georgas gears up his team to hit the ice at Varsity Arena.

This is how most intramural hockey is played at U of T: late at night with few spectators. Tonight, the engineering hockey team, the Skuleyard Bullies, is taking on U of T Scarborough. The game is played for fun, not glory.

“I love hockey,” says Damien Frost, a third-year engineering student and the Bullies’ right defenceman. “It’s great to play in an intramural setting because you know most of the people on your team. It’s like playing with your buddies.”

Georgas sends out his players to warm up with some passing and shooting drills. “Our players are from all different years,” he says. “It’s a way to get people together.”

Each year, about 8,500 students play intramural sports, participating in everything from triathlons to table tennis. While some of the teams play at a varsity level, there are divisions for all types and abilities – inner-tube water polo, for instance, for students who need help staying above the water-line.

Anne Richards, one of the nine sleepy-looking spectators in the stands, is here to see her son Mark skate for the engineers. “The teams only play five games in a semester, so if you miss one, you’ve missed a lot of the season,” she says. The late start time is fine with Richards: “It’s more convenient, actually,” she says, eyes on the ice. “This way, it doesn’t conflict with anything except sleep.”

Cast members of The Rocky Horror Show prepare for a midnight performance at Hart House Theatre

11:44 p.m.
“The Rocky Horror Show is a midnight kind of experience,” says Jenna Rocca, batting her fake eyelashes and adjusting her bowler hat. Rocca and her friend Bill Hulme have taken front-row seats at Hart House Theatre for UC Follies’ production of the cult classic, and they’ve dressed for the occasion. Rocca has chosen to wear a black bra as a shirt, and Hulme has smeared gold glitter on his bare chest. Rocca is what Rocky Horror veterans call a “virgin”: it’s her first time seeing a theatre production of the campy rock opera. “But I’ve seen it at least six times on video,” she says.

Rocky Horror is the raunchy tale of a transvestite alien, Dr. Frank N. Furter, who seduces an innocent couple, Brad and Janet, at his secluded mansion.

While the Hart House Theatre crew are resetting the stage for the midnight premiere, cast members speak about rehearsing for the notorious musical.

“It’s like no show you’ve ever been in,” says Peter Jermyn, who plays Rocky, the doomed title character. Flesh-baring costumes heighten the racy vibe – Jermyn wears little more than a shiny jockstrap. Not surprisingly, rehearsals centred on getting the actors comfortable with the revealing outfits. “We had to become, um, familiar with each other,” says Claire Burns, who plays Columbia, one of Furter’s “assistants.”

The hard work has paid off: tonight’s show is one of four sold-out performances.

“It’s almost midnight!” gasps Burns, checking her watch. “All the crazies are going to come out!”

12:28 a.m.
Fiona Rankin studies a set of graphs scrolling across her computer screen in the sleep laboratory at the Toronto Rehabilitation Institute on University Avenue. The graphs measure the breathing patterns, heart rates and brain waves of three patients. Rankin points to a long flat section in one graph. “This man essentially stopped breathing for a full minute,” she says.

Rankin, a technician, is working three 12-hour shifts this week. Most patients at Sleep Research Laboratory have sleep apnea, a condition that can cause them to temporarily stop breathing dozens of times a night. Heavy snoring is one indicator of apnea. In Rankin’s office, three Fisher-Price baby monitors, one for each patient, emit a gentle rumble.

“Did you hear that?” Rankin asks. “He started breathing again after 81 seconds. That’s a very long apnea.”

Dr. Douglas Bradley, a U of T professor and the laboratory director, is investigating how sleep disorders relate to cardiovascular problems. In a recent study, Bradley and his research team found a link between sleep apnea and the risk of stroke.

As for Rankin, she says that the rewards of assisting with this type of research are high, but admits that working at night takes a toll. “I have a lousy sleeping pattern,” she says.

1:07 a.m.
“In this lab, we study nematode worms,” says Mariam Alexander, a second-year master’s student in medical genetics. She and Alexandra Byrne, a third-year PhD candidate in medical genetics, are using the tiny worms to determine how specific genes affect muscle development and also how genes work together in the context of a whole animal.

Their lab is on the 12th floor of the sleek new Terrence Donnelly Centre for Cellular and Biomolecular Research, which offers a shimmery, nighttime view of downtown Toronto through its floor-to-ceiling windows. On any given night, you’ll find a handful of masters and PhD students in this lab, completing experiments, crunching data and compiling results.

“The worms have a three-day life cycle,” explains Byrne, so for students engaged in a complex experiment, that means working to the worm’s schedule.

“It’s a biological organism,” says Alexander, “so it’s not like we can turn it off and come back and continue the experiment. The worm will die, and then you lose everything.”

Byrne and Alexander, who have been working in the same lab for about two years, say the new Donnelly Centre labs are a vast improvement over the windowless rooms of the Medical Sciences Building, where they used to conduct research. “Here you can see the sun rise and set,” says Alexander, “There’s actually daylight.”

2:16 a.m.
“This is why we don’t have any glue sticks left,” sighs Claudia Calabro, reaching up to pull an errant tube of hardened glue off the ceiling where an anonymous prankster has stuck it. Calabro is the editor of the Gargoyle, University College’s irreverent, often satirical and sometimes plainly juvenile newspaper. Tonight the paper’s staff is working on its election issue.

Part of the Gargoyle’s enduring appeal is its grungy, handmade look, which comes from assembling it the old fashioned way – by cutting out pictures and text with X-Acto knives and gluing them onto large sheets of paper. About a dozen student staffers are gathered around the conference table – an abused billiards table, with the snooker balls lumped in the pockets – to survey the layout.

“We can’t tell this joke,” says someone at the far end of the table, arguing that it’s too tasteless, even by the paper’s risqué standards. An editor quickly renders the one-liner unreadable by crossing it out with a thick black Magic Marker.

“There are still four pages left to do,” Calabro hollers from her desk, where she’s writing her editorial. “We have to get everything done in half an hour or it won’t be printed tonight.”

Thirty minutes later, the edition is edited and glued down. Calabro shouts a victorious, “Somebody call a taxi!” The students clear the billiards table and bundle up the pages. Calabro and company head out into the cold and assemble on the front lawn of University College to see their baby into the cab that will rush it to the printer.

Robarts Library

3:24 a.m.
In a reading room at the Robarts Library, the students look either bored, desperate or deep in concentration. Several are completely unconscious.

Mai-Ling Truong, Joey Ng and Katherine Elton* are staked out at a table in the main lobby. They all have looming deadlines.

“I’m working on an essay on the Indian Act,” says Truong, a second-year Aboriginal studies student. “It was due today.”

Ng, a fourth-year life sciences student, is writing a book report about Filipino culture on the Internet. “It’s one of the most boring topics ever,” she groans.

Elton, a third-year political science student, is supposed to be writing about Quebec separatism for an essay that was due two days ago. “My enthusiasm is unparalleled,” she says, rolling her eyes.

The three are no strangers to late-night work, although Elton says that the frequency of their midnight study marathons varies. “Sometimes I don’t work late at night at all and sometimes five nights in a row.” It may not be for everyone, but it’s a system, says Elton, her friends typing furiously beside her. “We don’t usually wake up until 1 p.m., so this is our time.

4:05 a.m.
In the deepest reaches of the McLennan Physics Building on St. George Street is a room that’s crucially important to every student, and staff and faculty member – though few have ever seen it. Stored in this heavily air-conditioned bunker are the e-mail servers, payroll mainframes, Cray supercomputers and hundreds of other blinking, whirring and buzzing computers.

Network Operations (as it’s called) is like Grand Central Station, and it’s Sam Harrichand’s job as a shift supervisor to keep the trains running.

“See that red light?” asks Harrichand, pointing to a blip on one of the five monitors that indicate network traffic. “That’s someone launching an attack.” The hacker, location unknown, can’t find a chink in U of T’s armour. But other hacks have broken through.

“If the network goes down or the mail servers fail, I have to wake people up in the middle of the night to fix it,” he says. While such hacker attacks present a serious inconvenience, Harrichand says they make his job interesting. “I have to act quickly to get the network back in working order,” he says.

Harrichand blocks about a dozen attacks during a 12-hour shift, but the threats are mostly minor. “I like the work,” he says. “It’s quiet.”

6:01 a.m.
It’s windy and well below freezing, but in the attic at 91 St. George St., Jahmin Haye and Ricky “Turbo” Brown are heating up the airwaves with the rhythms of the Caribbean. Their radio show, The Morning Ride, is a mix of reggae and dancehall. Every Monday, it broadcasts live from 6 to 9 a.m. out of U of T’s community radio station, CIUT 89.5 FM. But today is no ordinary Monday: It’s Bob Marley’s birthday, and they’re dedicating a whole show to the music of the reggae legend.

“Today is going to be an extra-special celebration,” says Brown, introducing the show. “We’re celebrating the life of Robert Nesta Marley, born February 6, 1945, part of the Jamaican group the Wailers.”

CIUT’s signal has the largest broadcast reach of any campus radio station in Ontario. Today’s first caller, from Buffalo, requests “Could You Be Loved,” saying it’s his favourite Marley track.

“The Morning Ride” is consistently one of CIUT’s most popular shows, reflecting both the size of the Jamaican community in Toronto and the appetite for reggae generally. “You can’t stop the music, man,” says Brown. Haye nods in agreement.

After doing “The Morning Ride” for nine years, they still find getting up at 5 a.m. a little hard to take, but they’re dedicated. “It’s love, man, just a passion for the music,” says Haye. “It’s still not like a job because it’s …” he turns to Brown and asks, “What’s the word I’m looking for? It’s a responsibility.”

And with that, the red On Air light is back on. Duty calls.

6:25 a.m.
Through the windows of the Athletic Centre, the sky is a strip of dingy grey. Members of U of T’s swim team are wandering onto the deck of the pool for morning practice. Every sound in the humid, chlorinated air echoes sharply, yet it’s surprisingly quiet – just the sound of flip-flops on tile as the team members yawn, stretch, and get the kinks out before plunging in.

“I swim all five weekday morn-ings at 6:15, a little later on weekend mornings and then three nights a week,” says first-year student Hannah-Jo Ryan. “But if there was no coach on deck, I would have a tough time getting in this early.”

Each morning, the team spends two hours swimming laps and doing exercises to build strength and endurance and to improve their technique. For second-year student Marco Monaco, the training has paid dividends: he recently took silver and bronze medals in the breast-stroke at the Canadian Interuniversity Sport championships in Quebec City. The U of T men’s swim team placed third in all of Canada.

Such success requires exceptional dedication. “We train an extra half-hour a day just to take off tenths of a second,” says coach Byron Macdonald. “Marco happens to be one of the more intense trainers on the team.

“It’s the will to win,” says Monaco. “Getting up so early and having classes all day gets you really tired. But it all comes with what you do.”

The concentrated training schedule separates varsity athletes from other students. “You can’t really be like other people,” says Ryan. “A lot of my friends will stay up until 4 a.m., sleep through classes, and get up and do it all again. I can’t do that.”

The crack-of-dawn practices bring their own rewards, though. “If you start the day off with a really good workout, you feel great,” she says. “You feel like you’ve already accomplished something.”

7:55 a.m.
Pat Cave is now working days as a portress at St. Hilda’s College. But she has seen an awful lot of night shifts since beginning her career at the Trinity College women’s residence 40 years ago. “When I started working here, a young woman who wanted to be out after midnight had to go to the don and request a ‘late night out,’ and sign the book,” says Cave. “Then the don would give her a key.” Now the residents – both men and women – have their own floor keys. And there’s no one keeping a log of their nightly comings and goings.

In the 1960s and ‘70s, the women who lived at St. Hilda’s weren’t permitted men in their rooms, except on weekends. Weekday visits were restricted to “the pink room” – a large room on the first floor, where several visits often took place simultaneously.

Cave, who came to Canada from Guyana in 1964, worked as a cook for two years before starting at St. Hilda’s. Cave figures that she met thousands of students during her career – and got to know surprisingly many of them. “Some of the girls that live here now, their mothers were here,” she says. In February, Cave received a card from someone who had heard that she’ll be retiring in June.

With another shift beginning, and visitors coming and going under Cave’s watchful eye, she says she’s ready for retirement. But Cave intends to come back to visit. “Whenever I’m downtown, I can just drop in on St. Hilda’s and make sure it’s all in working order.”

*Katherine Elton is a pseudonym

The ratcheting temperature can be blamed on the tiny quarters: the 400-square-foot windowless studio holds 25 spectators and four maniacal comedians, who are performing improv for the pay-what-you-can crowd. A comedic version of rapier sword-fighting, improv is an intellectual sport in which each strike of an ad lib helps build a scene. The troupe members play off one-liners (or “offers”) that they throw each other, parrying and jostling their way to laughter or careening downward to a thud of silence.

Perhaps the most boisterous troupe member is U of T statistics professor Jeffrey Rosenthal – a six-foot-three, scruffy fellow with broad shoulders, a head of curly brown hair and a thunderous voice. (“He is Little John from Robin Hood,” says improv buddy Mike Ranieri. “A big, burly, lovable guy.”) Rosenthal ricochets from playing a son yearning for the acceptance of his housepainter father to a jilted housewife. Then – channeling a bellowing, frenzied version of Mel Gibson in Braveheart and adding the most diabolical Scottish accent outside Glasgow’s Barlinnie prison – he turns to a familiar role. He roars: “Alright then little boys and girls. It’s me first day teaching so I don’t want anybody giving me a hard time. That includes yew.” [looking at a cast member in a chair]

Student [cast member]: “Yes, Mr. Angus.”

Rosenthal: “Now look – I was told that you’re a difficult class. So here’s what I want you to do. I want you to just cower in fear and repeat after me: “I’m a miserable NOBODY.”

Students [cast members], en masse: “I’m a miserable nobody.”

Rosenthal: “You’re really not a bad class after all.”

Two weeks earlier, in his U of T office, Rosenthal wisecracks about what I will write if the performance flops: “He said he did improv but I went to the show and he’s actually an idiot. All his other work must be fraudulent, too.’” And comedy is a crapshoot, requiring a steely self-confidence and high-spirited sociability. Rosenthal, 38, started improv classes in 1995 at Theatresports in Toronto and began performing gigs after almost three years of training. “There’s a lot of randomness in how it goes, but when it goes well, and I actually make people laugh and enjoy themselves it’s exciting. And it also made me start thinking about other things differently…” He speaks of learning to “go with the moment” both on the stage and in the classroom. “Improv applies pretty much to your whole life – you’re always being confronted by things that you didn’t expect, or you couldn’t anticipate. And are you going to let it throw you off? Or are you going to embrace it and go with it?”

Embracing randomness – and being aware of its dangers and delights – is Rosenthal’s specialty. His latest book, Struck by Lightning: The Curious World of Probabilities (HarperCollins Canada 2005), shows readers how to use simple mathematical concepts – most notably, probability theory – to assess the odds of random events happening to them. In other words, how likely are you to actually get walloped by one of those rare occurrences that obsess you on a sleepless Sunday night? If, for example, you worry excessively about being the victim of a homicide, there is a chapter on how to assess crime statistics correctly. (According to Rosenthal, if we look at the difference between counts [total number of homicides] and rates [homicides per 100,000 people], we can see that the risk of being murdered in Canada has been on a slight decline since the mid-1970s – indicating it may be our fear of violent crime that is on the rise.) And during those raging late-summer electrical storms, it might be useful to know that only three Canadians died after being struck by lightning (as compared to, say, 74,824 of cardiovascular diseases) in 2001.

If, on the other hand, you hanker to beat the house at craps or 21 or blackjack, Struck by Lightning might help you calculate your odds. (Hint: rein in your inner Ben Affleck, and step away from the table – you’re not going to get rich quick. Casinos guarantee that games are weighted in their favour by employing probability theorists to calculate the average net payouts.) The book also includes chapters on understanding the margin of error in polling; interpreting medical studies; and – for those who vacillate over decisions large and small – utility functions (numerical ratings), which can help you decide whether to buy house insurance, ask out an attractive colleague or try a new medical treatment.

The book has clearly hit a public nerve: last year, it reached number seven on the Maclean’s bestseller list, and is now slated for release in the U.S., Germany, Australia, New Zealand, Japan and Italy. Struck by Lightning is an example of a publishing industry trend: books that merge an academic specialty with the concerns of a general audience. “The book shows how we can understand and interpret the events of our lives using simple math. If nothing else, it makes probability and statistics interesting and accessible for the layman,” says Radu Craiu, an assistant professor of statistics at U of T.

Rosenthal’s academic field is an exclusive one: he studies Monte Carlo algorithms (his specialty within this branch is an even bigger mouthful: Markov chain Monte Carlo randomized computer algorithms). In simplest terms, Monte Carlo algorithms are a way of using randomness to gauge quantities that are too difficult to compute directly. As Rosenthal explains in his book, they were first used at the Manhattan Project in New Mexico – birthplace of the atomic bomb – during the Second World War. Scientists needed to ensure the bomb contained the correct amount of uranium: too much, and it would explode prematurely, killing those surrounding the project. Using some of the world’s first computers, scientists randomly simulated the motion of neutrons and the atomic-bomb chain reaction over and over again. This allowed them to deduce how the neutrons would behave on average, and what fraction would escape. Monte Carlo algorithms are now used in almost every sphere where randomness exists: from managing investment portfolios to gauging which medicines work during trials. “One neat thing about probability, as opposed to many branches of mathematics, is that it is connected to so many things on a personal level and a professional one,” says Rosenthal.

In an early chapter of Struck by Lightning, Rosenthal explains how mathematicians invented Erdös numbers – a chain-of-connections game in which anyone linked to the gifted Hungarian mathematican Paul Erdös would be assigned a number value, with the most direct link receiving a number one. A Hollywood variation of the pastime, Six Degrees of Kevin Bacon, is now ubiquitous in the pop-culture landscape. And, given the number of U of T family connections Rosenthal has, anyone who has stepped on U of T soil might be able to play a new version of the game: Six Degrees of Jeffrey Rosenthal. His father, Peter, is a professor of mathematics at the university who specializes in operator theory. (For a decade, Rosenthal and his dad worked two floors apart in Sidney Smith Hall.) His mother, Helen, recently retired as a math lecturer at U of T Scarborough. Brother Alan is a computer science lecturer on the St. George campus, while brother Michael is an instructional technology analyst at OISE/UT. Jeffrey’s wife, Margaret Fulford, is the faculty librarian at the Faculty of Dentistry.

While Rosenthal was growing up in Scarborough, Ont., his numerically minded parents introduced him to mathematical concepts at an early age: by the time he was eight, he could prove the classic math idea that the number of prime numbers is infinite. He also had a working knowledge of probability theory, which he used to increase his chances of vanquishing his two brothers at Monopoly: he would compute the probabilities of his brothers rolling certain numbers on the dice and landing on certain squares, to decide whether to buy more real estate on his property. (Unfortunately, they employed the same tactics, making for some cutthroat Monopoly games.) And when he was a teenager studying math, physics and computer science at U of T in the late 1980s, he could envision “mathematician” as a profession in a way other undergraduate students didn’t seem to grasp. “For me, it seemed the natural career choice to work in mathematical sciences,” he says.

After graduating with a bachelor of science from U of T in 1988, Rosenthal attended Harvard University, earning a PhD in mathematics at the tender age of 24. It was at Harvard that he first began applying probability theory to everyday situations. In his second year, Rosenthal was slated to fly to the John F. Kennedy International Airport in New York to visit relatives – but a week before his departure, a plane crashed near the airport, killing 73 people. Rosenthal was skittish about getting on his flight, but found solace in the currency of cold hard numbers: he determined there were about 5,000 flights a week to the airport – and that the chances were probably less than one in 5,000 that, in the following week, there would be another disaster. The odds were low enough to convince him to board the plane. “At first I thought, ‘Oh my God there’s been a plane crash at JFK.’… It was only upon calming myself I thought wait a minute – I should stop and think about this more,” he says. “When you’re doing research work it tends to be so specialized that it’s easy to forget the connections to things around you. You’re working on your subtleties and you don’t look around so much. It was a case of trying to blend what I’m working on with the everyday.’”

Translating difficult concepts for a general audience, and playing to a crowd, are roles that come naturally to Rosenthal. Improv friend Ranieri explains how, a few years back, Rosenthal bought a video camera and solicited his friends to write and act in amateur movies with him. (One of their most recent pieces is the “Night of the Living Dead Christmas Special,” in which Rosenthal sings about “slay rides” and chomps on gifts of “brains” made of cauliflower.) The friends decided to create a movie trailer for Rosenthal’s first academic textbook, A First Look at Rigorous Probability Theory. “At first I thought, ‘What a stupid thing to do a movie on’ – a preview movie for this boring stats book. But we thought ‘That’s why it’s funny, right?’ so we did Rigorous Probability: The Movie,” says Ranieri. Rosenthal now shows the video to his graduate classes.

In the first episode of the hit TV show “My Name is Earl,” a two-bit thief finds a winning scratch ticket worth $100,000. In sheer revelatory joy, he punches the air, whoops with glee and dances his way out onto the road – where a senior citizen in a Buick slams into him, and sends his ticket casting off into the wind. While Earl is in hospital, his wife visits to hand him divorce papers, inform him she is having an affair with the local bar owner, and that her two children aren’t his. Stunned, drugged and imprisoned in a cast, Earl turns on the TV, and watches an interview with MTV personality Carson Daly – who is talking about how karma changed his life. “Karmaaaa,” says a gobsmacked Earl, who undergoes a spiritual epiphany. Convinced he is being paid back for a lifetime of bad deeds, Earl makes a list of all his wrongdoings – from siphoning gas to rigging a high school football game – and sets out to make amends with the universe. The result? While crossing number 136 (“been a litterbug”) off his list by cleaning up a motel parking lot, he finds the lost winning ticket in the detritus.

Is there karma? Is someone above taking notes and keeping score? When you’re a probability theorist, the idea of fate or the existence of the karma gods of Earl’s universe appear, well, highly improbable. In fact, Rosenthal is a member of the Humanist Association of Canada, a non-theistic group that believes life choices should not be guided by a belief in supernatural deities, but by human reason and compassion. Rosenthal speaks on the discord between fate and probability. “Often people will point to certain statistic examples: Here’s a good guy who almost died and then he didn’t and there must have been some divine intervention or master plan, but that’s what we the probabilitists would call a selection bias… You can just as easily find examples where the opposite happened: the bad guy got away and the good guy got killed. I say, well that’s perfectly consistent with the idea that these things happened randomly and that there is no all-powerful force controlling them,” he says. “To me it seems more useful to understand and deal with the world that we have and try to take actions that will improve the world based on what it is – rather than to ascribe things to it that there’s not evidence of.”

In October 1999, Rosenthal married Margaret Fulford in a humanist ceremony at Hart House: the service took place in the Debates Room, and the reception in the Great Hall. Rosenthal, an amateur musician (he plays everything from the trumpet and keyboard to the saxophone and bongo drums), sang and played guitar for his new bride. “The really romantic part was he sang a song that he had written for me when we had just been dating for six weeks, which was called ‘Margaret, Won’t You Fly to P.E.I. with Me?” says Fulford. “He also sang a Paul Simon song called ‘Kathy’s Song,’ which was the first song that he sung for me when we were first dating. It was very sweet.”

It’s a Wednesday afternoon, week 17 of the first-year seminar class “Probability and Uncertainty” in Sidney Smith Hall on the St. George campus. The room, with its austere windowless surroundings, is oddly reminiscent of the Bad Dog Theatre studio. The crowd is slightly smaller, and the laid-back atmosphere has a Sunday morning sleepiness, with students – in oversized sweatshirts, baggy jeans and caps – slouched low in their seats. Hardcover editions of Struck by Lightning sit on the maroon tabletops.

Rosenthal enters in a green sweater, khakis and beige sneakers. He begins talking at the hotfoot pace that he uses when he is enthused about something – which seems to be most of the time. Today the group is studying the “p-value” (the probability that an observed result occurred by pure chance) that is built into medical studies. Five per cent is the standard p-value, but Rosenthal wants the students to really think about what this means. He wants them to understand that it raises the possibility that one medical study in 20 might be wrong. “If we see something through observation, we always have to wonder if they just got lucky – whether shooting hoops or conducting medical studies,” he says.

He whips out a deck of cards, and his p-value performance begins. He tosses one club, one diamond and one heart to the student next to him and asks him to put the cards face down. “Question: do I have psychic powers?” Rosenthal looks at the back of the card, thinks hard, and guesses “clubs” – it’s a diamond. He misses on all three. “That seems to indicate I don’t have psychic powers.”

The mission extends to the students. With the enthusiasm of entering a game of Texas Hold ‘em, they gather in groups of two and three to try it for themselves. They do a series of telepathic “tests” – from staring at a facedown card, to inhaling over it, to running their fingers across it – to see if they can determine the card’s suit. (They must guess right three times in a row – 1/3 times 1/3 times 1/3 – to reach a statistically significant p-value of 3.7 per cent.) The jokers in the crowd make loud snorting noises during the inhaling segment. There are yells of “cheater.”

At the end of the trials, Rosenthal asks, “Who, according to current scientific standards, has psychic powers?” Three of the 17 students raise their hands. The talk parlays into what further experiments could be done to clarify results, and what tricks pharmaceutical companies could employ if they were desperate to get a new drug approved. “There is a flip side,” says one astute student. “Maybe a drug that could have saved lives was lost because there was too rigid a standard.” The students start thinking discriminately.

Before they leave Rosenthal runs over next week’s assignment: publication bias. It’s a loaded topic dealing with the medical-study controversy surrounding Dr. Nancy Olivieri and the pharmaceutical company Apotex. But he also asks them to read anecdotes in the book with names such as “Jumping Frog,” “Happiness Hat” and “Meditation Medical Miracles.” Because even in the curious world of probabilities, there’s always room for a little improvised entertainment.

Stacey Gibson is managing editor of U of T Magazine.

Herceptin is now available in Ontario, but its long journey to market underscores a profoundly difficult question for the people regulating the province’s strained health-care system. Do the overall benefits of such life-prolonging drugs exceed their considerable costs? For cancer patients, the answer is a resounding, ‘Yes, they do.’ But how much are we, as a society, prepared to pay for new drugs that purport to save – or prolong – a life? Is the sky the limit?

Dr. Murray Krahn, an associate professor in the department of Health Policy, Management and Evaluation at U of T, is an expert in cost-effectiveness analysis, a relatively young science that provides quantitative measures to help determine which drugs provide the most bang for the buck. “Cost-effectiveness analysis is kind of like a Consumer Reports for drugs,” says Dr. Krahn, the F. Norman Hughes Chair in Pharmacoeconomics. “It tells you whether a new drug is a good deal.”

In theory, says Dr. Krahn, cost-effectiveness calculations are straightforward. Analysts compare the cost of prescribing a new drug to the cost of using an older treatment – which could be a well-established pharmaceutical, or a combination of drugs and medical treatment. Experts in pharmacoeconomics then examine how the new therapy performs compared to previous treatments. They compare health benefits, such as long-term survival rates, tumour shrinkage, side effects and disease recurrence. The point is to assign a dollar value to the improved health promised by the new drug. This dollar value is what provincial drug plans should be willing to pay for the new therapy.

In practice, such calculations involve a complex array of clinical data and economic estimates. To illustrate the dif­ficulty of such calculations, Dr. Krahn points out that a cost-benefit analysis of an everyday consumer product is tricky because value is a malleable and fundamentally subjective term. For example, is a Volvo worth more than a Hyundai? The price suggests that it is, but the extra value offered by a Volvo may not be worth the additional cost. It depends how you measure the benefits of owning a Volvo. “Shopping for a car is hard enough,” says Dr. Krahn. “Health is way more difficult. There are millions of diseases and millions of interventions.”

Consider a new osteoporosis drug that promises to reduce the incidence of hip fractures. Among patients who are prescribed the drug, one can presume that hospital expenses – emergency-room visits, surgery, nurses’ salaries, administrative overhead – will drop. You need to estimate the total reduction in hospital expenditures and weigh it against the cost of administering the drug.

Mike Tierney (BPharm 1978), the director of the Common Drug Review at the Canadian Coordinating Office for Health Technology Assessment, an independent agency that conducts such evaluations, says hospitalization costs can be estimated using data collected by the Canadian Institute for Health Information. The tricky part is that hospi­talization rates vary significantly from province to province (and even from region to region) due to, for example, home-care policies and different treatment approaches. The point: the relative value of a new drug may vary depending on where it’s administered.

Even more difficult is gauging the effectiveness of a new treatment against previous therapies. Health Canada approves a drug based on how well it performs in experimental trials. The problem is that drugs behave differently in the real world, where a patient’s lifestyle – whether he misses pills, smokes, drinks, or dines predominantly on potato chips – can undermine a drug’s effectiveness. What’s more, trials offer limited data on how a new drug will fare in the long run. “This is one of the problems of going through with this kind of evaluation,” says Dr. Krahn. “People are called upon to do economic evaluations when the data isn’t as a mature as you’d like.”

Dr. Andreas Laupacis, president and CEO of the Institute for Clinical Evaluative Sciences and a drug evaluation expert in U of T’s Faculty of Medicine, cites the example of Iressa, a lung cancer therapy that was approved for use in 2003 on the basis of its promising performance in trials. “My understanding is that when it was evaluated in patients over the long term, the benefits were marginal,” he says.

The potential for miscalculation has some clinicians and epidemiologists complaining about the lack of standards in making evaluations, which are typically conducted by drug companies. Dr. Krahn says this skepticism is well deserved. “Cost-effectiveness evaluations are exponentially more complex from a design point of view than randomized controlled trials and more subject to the bias of the investigator.” In Australia, a 2000 review of 326 drug applications to the country’s Pharmaceutical Benefits Scheme found “significant problems” with two-thirds of the pharmacoeconomic evaluations conducted for the board, including biased or incomplete studies. In other words, evaluation experts may be basing decisions about whether or not to approve a drug on shaky economic analysis.

Equally contentious is what such studies actually reveal. When a new drug is subject to cost-effectiveness analysis, it results in a number that purports to tell policy-makers approximately how much extra cost a drug plan can expect to incur each year of a new treatment for one patient to achieve an improvement in quality of life. In a highly controversial 1992 paper that Dr. Laupacis wrote to provoke debate, he proposed that new drugs approved by Health Canada that have a net cost of less than $20,000 for each year of treatment per patient be deemed affordable and included on provincial drug plans, while those north of $100,000 be considered too pricey. “People asked, ‘Where did you come up with those numbers?’ The answer is, ‘We made them up.’”

Tierney insists that policy-makers don’t rely only on hard-and-fast thresholds to determine whether a new drug is too expensive relative to the benefits it provides. Still, many in the field regard $50,000 as the unofficial line separating overly pricey from affordable treatments. But, as Dr. Krahn observes, “No one knows what threshold we should be using. It’s a question of how we value some standard unit of health.”

With very expensive cancer drugs coming onto the market all the time, can Canada’s ailing health care infrastructure continue to bankroll these therapies without forcing financial sacrifices on other parts of society?

Most observers say the answer is political, but policy-makers still need to be able to tally up the actual costs and benefits. As Dr. Krahn puts it, cost-effectiveness evaluations are “a very powerful way of supporting decision-making.” Yet a pair of McMaster University health policy experts published a study in the Canadian Medical Association Journal in 2003 that cast doubt on whether cost-effectiveness analysis serves to contain overall drug expenditures. Arguing that the use of such evaluations is “a prescription for increased expenditures,” Amiram Gafni and Stephen Birch noted that the addition of a costly new drug to the provincial drug plan tends not to accompany cost reductions elsewhere in the system. As Dr. Laupacis points out, “Most drugs don’t replace older drugs; they expand the market.” In other words, as a greater number of drugs are approved, more drugs are being prescribed – and that means higher overall costs.

“What you fund is not a purely technical question,” says Dr. Peter Singer, the director of U of T’s Joint Centre for Bioethics and the Sun Life Financial Chair in Bioethics. Drug approvals must involve what he calls the “three Es” – evidence, economics and ethics. In his view, a cost-effectiveness assessment is necessary but insufficient. “The fundamental question is how much benefit a particular drug should have, and at what cost, before 13 million Ontarians are willing to pay for it,” he says. “There’s no straightforward answer.”

John Lorinc (BSc 1987) is a Toronto writer. His book The New City was just published.

“What tempo?” Salverda asks.

“Whatever you think you can execute,” Nachoff suggests.

Accompanying Salverda are fellow students on standup bass, drums and piano. Together they quickly map out how they’re going to play, and the bass player mumbles, “One, two, three …”

The music begins. What was an informal exchange of ideas between players becomes a surprisingly accomplished rendition of a standard from the Big Band era. Closing your eyes, you’d think you were in a real jazz club.

But just when the musicians are really swinging, Nachoff waves at them to stop. They resume their insiders’ talk. Being able to improvise around a central melody is a key skill for any jazz musician, and learning how to do this involves constant playing and reviewing. “When you get to performing, you have all the freedom you want,” says Nachoff. “But you have to practice specific elements of a piece over and over.”

The cluttered performance room at the Faculty of Music is not far from Toronto’s downtown jazz clubs, but the journey from one to the other is a long haul. Students enrolled in U of T’s four-year jazz studies program practise and perform about 40 hours a week while also writing essays and exams. Many do paying gigs on the side: Salverda plays in a mariachi band at a Mexican restaurant; other students sit in on sessions at The Rex, a downtown blues and jazz bar. They are required to compose their own music, study music history and theory, and arrange songs into a jazz format (reinventing the Beatles’ “Yesterday,” for example, as a jazz instrumental). On a practical level, students also learn how to market themselves as musicians and manage their business affairs. Most will not make a full-time living from jazz. But they are all committed to trying.

Professor Terry Promane, the director of U of T’s jazz studies program, says younger students usually find improvisation class the toughest. “At first, most people can only handle a very basic set of chord changes.” He illustrates by singing, “Five foot two, eyes of blue,” emphasizing the nursery rhyme-like simplicity of the song. “By the time the students are finished, they’ve progressed to a sophisticated and professional level.”
Students receive an hour a week of private lessons from a faculty member, which can yield significant skill improvements, says Promane. “Students come to you as a big block of granite, and every lesson you knock off another chunk. By the time you get to fourth year, you hope the statue is complete.”

Despite the gruelling work and high expectations, the young musicians seem to welcome the intensity of the learning experience. “Any one-on-one you get can only be beneficial if you really want to learn to play your instrument,” says Salverda.

But can jazz – the heady brew of syncopation, improvisation and rhythm created by African Americans in the early part of the 20th century out of their other monumental musical invention, the blues – really be an academic pursuit? Isn’t it best learned in a dark club over shots of bourbon?

That’s something of a Hollywood stereotype, but Gage Averill, dean of the Faculty of Music, believes that students do have to make a serious decision about how they want to learn jazz. “If you want to throw yourself into playing 24/7, don’t do this. This is for people who want a degree – who want to stretch their mind, to think about what modernism and post-modernism mean because they don’t think music is just about playing. Our students get the university experience and they continue to polish their craft with really good teachers.”

Those “really good teachers” are a major draw for students. “Everyone who teaches here is a jazz player,” says Promane, an accomplished trombonist who played with Rob McConnell’s famed Boss Brass. “We discuss the music as a classical art form. The conversation always circles around the large body of the jazz canon and the jazz mindset.”

U of T’s Faculty of Music launched the jazz program in 1991 with the goal of providing an intimate kind of music instruction. “You have to get to know your students personally so you can help them artistically,” says Prof. Paul Read, the program’s founding director, who now heads up the master’s program. “With 65 students, you have a far better opportunity of doing that than if you have 300.” Read worked with Canadian jazz legend Phil Nimmons (who is still a faculty member at age 82) to design the program. They hoped their students would take an interest in different styles of music. “We wanted students who were interested in broadening their scope,” says Read.

Before North American universities began teaching jazz in the 1950s and 1960s, most faculties of music offered programs in classical music and opera, which were considered a better fit with a university’s academic approach. “That feeling kept jazz out of universities for a long time,” says Read. “But music is music. There are more similarities between learning to play music in the jazz idiom and the classical idiom than there are differences.” He says jazz has suffered from some unfair stereotyping. “This music has come a long way from the dance hall or the smoky bar. It still has those dimensions, but it is also a very sophisticated art form with a wide range of expressions.” Still, there are risks to submitting jazz to the rigours of academe. “One of the biggest challenges we face is to not kill off the spontaneous street character of the music by taking an overly academic approach,” says Read. “You can throttle it by talking it to death and overanalyzing it.”

Performance remains a focus of the program. And students say the daily exposure to veteran jazz musicians is crucial. Last October, Dan Fortin, a third-year bassist from Peterborough, Ontario, was the accompanist with Canadian jazz guitarist Lorne Lofsky in a master class (where prominent professional musicians participate with students in a mix of performance and detailed analytical discussion). For Fortin to be able to play alongside Lofsky is akin to an aspiring novelist getting Margaret Atwood (BA 1961 VIC) to review a first draft.

“This is the great thing about arts education,” says Fortin. “It’s about finding people who are working in the medium. They guide you and show what can inspire you. They don’t say ‘This is what you need to learn.’ They allow you to do your own thing.”

The program also balances the artistic exploration of jazz with the practical realities of building a career. Vocal instructor Heather Bambrick (Mus Bac Per 1997) – a recent winner of two National Jazz Awards – says what she learned from singer and former U of T instructor Carol Welsman was invaluable. “I could pick her brain and say, ‘How do I do a demo? How do I organize my first band or my first record?’ The one-on-one time students have with the instructors is pretty amazing.”

Another U of T faculty member is Chase Sanborn, a veteran studio musician and former member of the Ray Charles Orchestra. Sanborn encourages young musicians to consider the business side of music and to develop a career strategy. At a clinic he gave for U of T students last fall, he offered advice on marketing, promotion, and finances and taxes. “The program should be about learning to do what you do, but you also need to keep your mind open to how to make a living,” says Sanborn.

What drives these young people to pursue the life of a musician? Not riches or superstardom. Although several U of T alumni have gone on to international prominence, not many musicians can devote their careers to playing only jazz. This might have been possible in the 1930s and ’40s during the Swing Era, when the bands of Duke Ellington and Artie Shaw were at the height of their popularity and Ella Fitzgerald and Billie Holiday topped the charts. But in the 1950s, rhythm and blues and rock ’n’ roll came along and captured the minds and ears of a younger generation. Jazz continued to evolve, with the emergence of Charlie Parker, Miles Davis, John Coltrane and such new styles as bop and fusion, but it never regained its mainstream popularity. Although a vibrant jazz scene still exists around the world, most professional jazz musicians flesh out their incomes with composing and arranging, teaching, corporate Christmas parties and stage musicals.

Faculty member Phil Nimmons understands a musician’s passion for jazz and the drive to play, despite the financial difficulties that can come with it. For decades, his bands (Nimmons ‘N’ Nine and Nimmons ‘N’ Nine Plus Six) practically owned the Canadian jazz scene. But that’s not how his career started. While attending the University of British Columbia in the 1940s, Nimmons planned to become a doctor. As talented as he was in the sciences, however, he couldn’t let go of music. “I think this is something you can sense in our students. They have this desire. This is what they want to do.”

Like Nimmons, most musicians – pro and student alike – find it difficult to put their passion into words. Jazz piano virtuoso Bill Evans once described his interest in Zen Buddhism this way: “I don’t pretend to understand it. I just find it comforting – and very similar to jazz. Like jazz, you can’t explain it to anyone without losing the experience. That’s why it bugs me when people try to analyze jazz as an intellectual theorem. It’s not. It’s feeling.”

Third-year student Fortin spends a lot of time in class talking about jazz, but he says the difficulty of explaining the music is part of its attraction. “Sometimes you can’t really explain what you love about jazz or why it affects you. And that makes it satisfying and mysterious.”

Paul Fraumeni is the editor of U of T’s research magazine, Edge.

The Players
Visit jazz clubs or festivals, or enrol in a jazz program at a North American school, and you’re likely to encounter a graduate of U of T’s jazz studies program. Among the most well-known U of T jazz alumni are:

Lina Allemano, trumpet
2005 CBC Galaxie Rising Star Award

David Braid, piano
2005 Juno Award winner for traditional jazz album of the year
Tara Davidson, saxophone
Winner of the 2005 Distillery Jazz Festival “Emerging Artist Award”

Andrew Downing, bass
Eaton Graduating Scholarship winner from the Faculty of Music (1996). His band, Great Uncles of the Revolution, won the 2004 Juno Award for contemporary jazz album for “Blow the House Down”

Mike Malone, trumpet
One of Canada’s leading jazz composers; member of the Dave McMurdo Jazz Orchestra; faculty member at Mohawk College

Mark McLean, drums
Jazz Report Post-Secondary School Musician of the Year in 1998; has since played with Oscar Peterson, Jane Bunnett and Molly Johnson, among others

Anthony Michelli, drums
Jazz Report Post-Secondary School Musician of the Year in 1995; winner (with the Nancy Walker Quartet) of the 2003 Grand Prix de Jazz General Motors at the Festival International de Jazz de Montreal

Dariusz Terefenko, piano
Faculty member at the Eastman School of Music at the University of Rochester

Another thing to know about Reilly is that he doesn’t turn up his nose at the gifts of serendipity. Consider this anecdote:

The University of Toronto professor, who is also a scientist with the Toronto General Research Institute, had been anxiously trying to find a source for a rare biological substance that he needed before his therapy could proceed to clinical trials. He had exhausted his options through traditional avenues. He was, he says, at wit’s end. So late one evening, as a last resort and expecting nothing, he turned to Google.

Reilly typed “pharmaceutical quality epidermal growth factor” into the search engine and, to his surprise, the query produced three hits. The last link, from a biotechnology company in Ithaca, in Upstate New York, turned out to have the stock, the quality of material and the desire to supply research efforts such as Reilly’s. Nine months later, Reilly’s unique targeted radiation therapy was being tested on breast cancer patients in Canada, the first in the world to receive the breakthrough treatment.

To know Raymond Reilly’s story is to understand a lot about the story of new cancer therapies: they almost never involve a smooth trajectory from stunning laboratory results to patient benefits. More often, the tale is an epic of wrong turns, aggravating switchbacks and the infrequent interventions of fate. Above all, the narrative is one of perseverance. But when researchers such as Reilly prevail, the world ends up with ever-more sophisticated, effective therapies to beat back mankind’s most flummoxing diseases. In other words, the endings of such tales can be very satisfying indeed.

Cathie Long (BA 1971 Trinity) is an accountant, a mother and an avid French horn player. But ask her to explain Reilly’s unique treatment, and she sounds a lot like a biophysicist. Long, 56, has a vested interest in understanding how and why Reilly’s approach has potential in the fight against breast cancer.

Long, who lives in Cobourg, Ontario, found out she had aggressive breast cancer in 1995. She underwent surgery, chemotherapy and radiation, then enjoyed nearly seven years of remission. But in 2002, she felt a pain near her sternum that turned out to be cancer; the disease had metastasized. Since then, she has tried radiation treatment and four separate chemotherapy regimens. She suffered from fatigue, hair loss, gastrointestinal effects and a blood disorder in the process.

The Canadian Cancer Society reports that nearly 150,000 people in Canada were diagnosed with cancer in 2005. Although lung cancer is still the leading cause of cancer deaths among adults, breast cancer continues to affect more Canadian women than any other form of the disease.

In the past 20 years, the understanding and treatment of cancer has been helped immeasurably by genomics. The sequencing of the human genome, completed in 2003, has enabled researchers to identify a host of genetic targets in cancer cells and develop new therapies. Recently, a related field called functional proteomics has energized cancer research. This specialty identifies the proteins produced by genes, and proteins are often the first warning sign of disease.

Long has a type of breast cancer that produces a particular protein. Those with breast cancer producing this protein tend to have a poorer prognosis than those with other forms of the disease. As it happens, Reilly’s novel therapy targets precisely the kind of breast cancer cells that are invading Long’s body. His treatment takes the old workhorse therapy of radiation and makes it more deadly, more effective and less toxic by getting it inside these individual cancer cells.

Long was asked to take part in the earliest human experiments with Reilly’s targeted approach, and she decided to opt in. “I had developed resistance to chemotherapy, and I wasn’t a candidate for [the cancer drug] Herceptin,” she says. “The approach of delivering radiation in a really targeted way made sense to me.”

Like so many researchers throughout the history of science, Reilly stumbled on a new way to treat cancer while looking for something else.

For much of his career, Reilly made radiopharmaceuticals. These compounds emit gamma rays that are captured by sophisticated cameras and produce images similar to a CT scan. They help radiologists “see” disease, infection or injury in the body. Different radiopharmaceuticals can help visualize different ailments. And early on, Reilly began thinking about designing radiopharmaceuticals that help doctors detect specific kinds of cancer.

His work in imaging and diagnosing disease led to his interest in designing a radioisotope that would not only locate breast cancer, but also tell doctors about the idiosyncrasies of each tumour. “Breast cancer is not just one disease, though often it is treated that way,” he says. “Tumours differ because of their biology. Some are more aggressive than others.”

Tumours, like cats, can be very finicky about what they eat. Reilly wanted to understand the specific growth factors, or proteins, preferred by the tumours of different breast cancer patients. The rationale was simple: the more information doctors can have about the specific diet of each tumour, the better they can use drugs and other therapies to interfere with the diet that allows the tumour to grow unchecked.

Cancer specialists were already well aware that certain breast cancers have a healthy appetite for the hormone estrogen. Inside these cancer cells are entities called estrogen receptors, which attract the hormone and absorb it directly into the cancer cell nucleus, where it triggers cell growth.

By the time Reilly began his doctorate work in medical biophysics in the mid-1990s, these estrogen-receptor-positive breast cancers were being successfully treated with drugs such as tamoxifen, which inhibits the cancer cell’s ability to take up estrogen and slows cell growth. But not all breast cancers are hungry for estrogen. Reilly became interested in another kind of tumour, which is harder to diagnose and treat. “I wanted to identify patients with a poor prognosis – those who don’t respond to tamoxifen and who might need to be treated more aggressively with chemotherapy,” he says.

By poring over research literature, Reilly found that breast cancers that don’t feed off estrogen have another kind of receptor – one that attracts a peptide called epidermal growth factor (EGF), which is produced by the body’s salivary glands.

Reilly speculated that if he attached a radionuclide to EGF, it would act like a homing device and take the imaging tracer directly to cancer cells with EGF receptors. The radionuclide would cause the EGF-receptor-positive tumour to light up on the camera image, creating an easy, accurate and non-invasive way to diagnose this more stubborn subset of cancer tumours.

So in 1996, Reilly was well on his way to developing a helpful new imaging agent. Little did he know that the fickle gods of research had something a little different in mind. In the midst of his doctoral work, Reilly attended a meeting of the Society of Nuclear Medicine where he noticed a research poster that only a radiopharmacist could love. It described how a decaying radiopharmaceutical (a form of iodine 125) could damage a cell’s DNA by emitting Auger electrons. Named for the French scientist Pierre Auger, who first published research on them in 1925, these electrons have a low energy and can only travel short distances – mere nanometres. But this is all that’s needed to wield a hefty blow within the confines of a cancer cell nucleus.

Reilly was dumbstruck by the enormity of the possibilities. He was using another Auger-electron emitting radioisotope called indium-111 for his work on a new imaging agent. It occurred to him that the tool he was developing to better diagnose EGF-receptor-positive breast cancer might actually end up treating it.

When scientists try to decode their complex drug delivery work to a lay­person, they often use metaphors of weaponry and stealth: the smart bomb versus the carpet bomb, or the sniper versus the indiscriminate machine gun. Way back in 1996, Reilly started to think of his potential new therapy as a Trojan Horse – a way of smuggling a deadly payload into enemy territory under the guise of something friendly. He had a good hunch that if he attached indium-111 to the EGF peptide (to create an EGF conjugate) it would be taken inside EGF-receptor-positive cancer cells. And he bet that when indium-111 started decaying in the cell, the emitted Auger electrons would be close enough to the cell nucleus to irrepara-bly damage its DNA. In other words, he planned to exploit the cancer cells’ appetite for EGF by feeding them what they wanted – and smuggling a radioactive ambush into each cell.

Back in the lab, Reilly found that radio-labelled EGF could actually kill breast cancer cells. In fact, when Reilly compared his indium-111 EGF conjugate to the conventional chemotherapy drug methotrexate, the conjugate was 300 times more toxic to cultured breast cancer cells. Never in his professional life had he come this close to yelling, Eureka! “I couldn’t believe it,” he says.

Last October, Long got her one-and-only intravenous treatment of indium-111 EGF as part of the Phase 1 clinical trial for the therapy. Her ears momentarily turned red. Her blood pressure dipped slightly. And, for a brief moment, she felt nauseous. Small stuff.

Long kept her sense of humour, especially about the precautionary measures. She wasn’t allowed to sleep next to her husband for the first week. She also had to flush the toilet three times after using it, keep her towels separate, stand back a few metres from anyone she encountered and avoid public transportation. Because indium-111 is a radionuclide, it’s regulated by the Canadian Nuclear Safety Commission – and that means lots of precautions.

“It was overkill really, but in terms of inconvenience it is minor compared to six months of chemotherapy,” says clinical scientist Dr. Katherine Vallis, a U of T associate professor of radiation oncology and medical biophysics.

Several years ago, Vallis, who is also a radiation oncologist at Princess Margaret Hospital, joined forces with Reilly to get his therapy ready for clinical trials. Together, they’ve spent much of the intervening years proving that indium-111 EGF is worthy and safe for testing on humans.

EGF receptors are not only produced by specific cancers, they occur on the surface of healthy cells in the liver and kidneys. The team had to show that the indium-111 EGF conjugate would not be unduly toxic to these organs or the bone marrow. Once they developed animal models to test their therapy, they were in for a happy surprise: even at 42 times the planned maximum dose for humans, the new therapy tested on mice resulted in no toxicity to the kidneys, liver or bone.

Despite these cheery results, the process of obtaining Health Canada approval for their clinical trial had as many ups and downs as a barometer in spring. (Pharmaceutical companies have whole departments dedicated to ensuring that promising drugs make it through the rigorous government approval process. Academic researchers, such as Reilly and Vallis, must deal with all of the paperwork themselves.) “Certainly there was a point where we thought the regulators were demanding so much that we did some heart-searching about what our role was – if, in fact, we should just do the preclinical work and leave the actual trials to someone else,” says Vallis.

In total, it took 18 months and 1,300 pages of documentation to gain Health Canada approval. In his office, Reilly devotes most of a long shelf to the fat white binders that house these documents.

“It was the worst-case scenario,” says Reilly. For starters, the team was testing a conjugate that had never been pre­viously studied in humans. Also, the conjugate was a radiopharmaceutical – one that emits radiation. Finally, the radioisotope was attached to EGF, a biotechnology product that itself attracts a high level of regulatory scrutiny.

In January, the Phase 1 clinical trial of indium-111 EGF was 18 months old and six months shy of completion. The team has gradually increased the dose levels throughout the trial in an attempt to determine the highest dose that can be safely administered. So far the Phase 1 trial has confirmed that indium-111 EGF is safe for human use.

This confirmation is fuelling a lot of plans. Reilly and Vallis are exploring new clinical-trial possibilities for other cancers that express EGF receptors. They’re also considering the potential of conjugating the breast cancer wonder drug Herceptin to indium-111. They hope the result would combine the super drug’s growth-inhibiting factors and the Auger electrons’ cancer-killing properties to deliver a one-two punch to cancer cells. And they are looking for an industrial partner to help them move their indium-111 EGF breast cancer therapy to the next level of clinical trials. If these trials are successful, and the team continues to receive funding, the novel treatment could be approved for use by the end of the decade.

Long received only one injection and at a low dosage. Since then, she has made the 80-minute trip between Cobourg and Toronto for hours of followup. And yet for someone with a lot at stake, she keeps a sublimely practical outlook.

“I feel justified in saying that whatever the outcome of this particular clinical trial, even if it doesn’t go the way I hope, things will be learned from it to use for the future,” she says. “My cancer is slow-growing though incurable and progressive. So there is a little time to experiment on me, and it’s my way of giving back to the people and the whole system.”

Certainly Long understands as well as the researchers that developing a new therapy can move as slowly and in as tiny increments as an Auger electron. But if the ultimate effect is precise and inexorable, she figures it will be worth the risk she decided to take. Reilly meanwhile, is keeping counsel with the type of optimism that researchers who’ve faced a mountain of challenges are best at – the guarded yet hopeful kind.

Krista Foss is a writer in Hamilton, Ontario. She wrote “Miracle at Sick Kids” in the Summer 2005 issue.

This is where Christine Allen comes in. To get these drugs to where they’re supposed to go, the assistant professor of pharmacy at U of T is building nanoparticles to encase the drug molecules. Then she targets these nanoparticles to breast cancer cells in much the same way as her colleague Raymond Reilly targets his radiotherapy. She attaches them to epidermal growth factor peptides, which smuggle the nanoparticles inside the cancer cells where the encased drug is released. Her creations are so small that she has to use an electron microscope to see them.

Allen, whose doctoral work was in polymer chemistry, researches her unique nanoparticles in a distinctly high-tech fashion. Using software that produces 3-D images, she creates virtual models of the new materials used to make up the particles on the supercomputer at the Molecular Design and Information Technology Centre, a leading Canadian academic bioinformatics centre devoted to drug design. Allen says the centre’s software predicts how these materials will interact with the drug they’re carrying – helping her rule out certain designs and saving the inestimable expense of making mistakes in the lab.

While the work of this avowed “chemistry geek” is still in the early stages, she is beginning to test some of her unique compounds on animals. And she has plans to collaborate with other scientists, such as Reilly, to create hybrids of their targeted approach. “As a material scientist working in nanotechnology, I couldn’t be in a better institution,” says Prof. Allen, who appreciates being in close proximity to other like-minded researchers at the Leslie Dan Faculty of Pharmacy. “I can just walk down the hall and get answers to all sorts of questions.”

The $75-million Leslie L. Dan Pharmacy Building at College Street and Queen's Park Crescent houses state-of-the-art laboratories, lecture halls and two unique "suspended" classrooms

The brand new $75-million facility at the northwest corner of College Street and Queen’s Park Crescent is a sunlit cathedral of glass and black granite. It’s a far cry from the cramped maze and winking fluorescent lights of the circa-1960s Russell Street building that the Leslie Dan Faculty of Pharmacy currently calls home.

While faculty and students will soon be able to appreciate the state-of-the-art research laboratories, the design by architects Foster and Partners of London, England, is nothing short of an esthetic marvel. The panes of glass forming the five-storey atrium are so large they had to be ordered from Luxembourg – the home of the world’s only supplier that would cut the panes that big. The glass allows an unobstructed view of the elegant heritage buildings next door – the Tanz Neuroscience and FitzGerald facilities.

Inside the light-filled atrium, two large pods float overhead like smooth white eggs. Inside the larger “egg” is a 60-seat classroom; the smaller one contains a 24-seat computer training centre. These suspended classrooms could not have been built five years ago, says Darren Lobo, the project co-ordinator for PCL Constructors Canada, the firm heading the construction. The computer software to design them simply didn’t exist.

The spacious six-storey cube on top of the atrium will house research and administrative offices, laboratories and unique teaching environments, such as the Herbert R. Binder/Shoppers Drug Mart Professional Practice Laboratory. This lab will give pharmacy students practice in counselling “patients” (played by actors). Their interactions can be taped and observed by classmates and professors through a closed-circuit television system. In the building’s basement are two large lecture halls – 240 and 300 seats – stacked on top of each other, like the Elgin & Winter Garden Theatre Centre a few blocks away.

Leslie L. Dan (BScP 1954, MBA 1959, DScP Hon. 1997), chairman and founder of Novopharm, donated $13 million to the construction of the cutting-edge facility. Apotex and Shoppers Drug Mart are also major contributors, along with the province of Ontario and the University of Toronto. The new building, which opens in September, will enable the Leslie Dan Faculty of Pharmacy to double its enrolment to 240 students in the undergraduate pharmacy program and significantly increase the number of faculty, researchers and graduate students.

“The private sector must play a greater role in ensuring that we help meet the need for a greater number of skilled profes-sionals in the province’s pharmacies,” says Dan. “On a personal level, as a U of T alumnus, I feel it is incumbent upon me to give something back – something that will benefit the university and society. The University of Toronto provided a great start to my career, and now I want to make certain others benefit from those same opportunities.”

Yet as much as we know about the frequency with which cancer strikes, we still don’t know all that much about its causes or how to stop it. Dozens of doctors and professors at U of T, as well as thousands around the world, are investigating how cancer cells behave and trying to find better ways to slow their growth, eliminate them or prevent them from forming in the first place.

A promising avenue of research, which is being followed at U of T’s Leslie Dan Faculty of Pharmacy, focuses on how to deliver cancer-fighting agents to precisely where they’re needed in the body. Too often, the therapy dissipates before it arrives at the site of the cancer, or harms healthy cells while attacking cancerous ones. Professor Raymond Reilly, whose research centres on a relatively uncommon form of breast cancer, is trying to circumvent these problems by attaching a radioactive cancer-killing agent to the protein in the body that fuels the tumour’s growth. Krista Foss reports on Reilly’s promising “Trojan Horse” treatment as part of a feature highlighting the new Leslie L. Dan Pharmacy Building (“A Twist of Fate”).

It’s human nature to imagine the worst. So when statistics professor Jeffrey Rosenthal learned a week before he was slated to fly to New York City that an aircraft had crashed at the city’s John F. Kennedy International Airport, he naturally worried that his plane would be next. Then he discovered that the airport handles 5,000 flights a week, and figured he was probably safe. As U of T Magazine managing editor Stacey Gibson notes in her profile of Rosenthal (“Games of Chance” ), the 38-year-old probability expert, who moonlights as an amateur comedian, is adept at explaining to students and lay audiences how mathematical concepts, such as probabilities, play an important role in our daily lives.

Classes are a vital part of the U of T experience, but an awful lot occurs outside of the lecture hall – sometimes at unusual hours. Varsity editor Graham F. Scott explored the St. George campus over several nights in February (“After Hours” ) and spoke to students conducting experiments, playing sports, writing, performing, broadcasting, and yes, even studying. In the wee hours of the night, what shone through was the students’ dedication – to the task at hand, and often to a greater goal – and desire to succeed. As second year-student and varsity swimmer Marco Monaco put it: “It’s the will to win.”

In 2005, for example, Maclean’s ranked the University of Toronto number one among Canadian medical-doctoral institutions for the 12th year in a row. It’s a fabulous record. However, during my academic career in healthcare performance measurement, I learned to be wary of aggregate rankings of institutions. Imagine a hospital that was superb at heart surgery but had a mediocre obstetrics program. The combined rating for those two programs would be useless for heart patients and expectant women alike! It’s much the same when complex universities are reduced to a single score.

For better or worse, the seductive reductionism of institutional rankings still gets attention all over the world. One popular “league table” is published by the Times Higher Education Supplement. The Times ranked U of T 29th on its annual list of the world’s top 200 universities, up eight spots from our 2004 ranking. We were the top Canadian university in biomedicine, science, social science and technology, but stood fourth in arts and humanities and ended up slightly behind McGill overall.

Another popular global ranking is published by the Institute of Higher Education at Shanghai Jiao Tong University. Their system put U of T 24th in 2005, top among Canadian universities, with UBC and McGill respectively second and third in Canada.

Why the differences? The Times creates a composite score by combining reputation ratings, research outputs, proportion of international students and faculty, student-faculty ratios and survey data from employers or recruiters. The Shanghai scoring system relies overwhelmingly on research performance measures.

In January 2006, Alex Usher and Massimo Savino from the independent Educational Policy Institute took a constructively critical look at university league tables worldwide. They noted that within individual countries certain institutions invariably rise to the top, regardless of the ranking scheme: Oxford and Cambridge in the U.K.; Harvard, Yale, Princeton, MIT and Stanford in the U.S.; Peking and Tsinghua in China; and the University of Toronto in Canada. But the authors also cautioned that the basis for this convergence remains mysterious.

Their trenchant observations reminded me of Northrop Frye’s description of human thought – “a process stumbling through emotional entanglements, sudden irrational convictions, involuntary gleams of insight, rationalized prejudices, and blocks of panic and inertia, finally to reach a completely incommunicable intuition.”

I am delighted, of course, that “incommunicable intuition” confirms our top Cana­­dian ranking. That aside, we really need hard data to guide us as we strive to make U of T an even better university. That’s why U of T has worked for years to develop and refine its own performance indicators. And that’s also why we publish an array of indicators that hold our institution up to critical scrutiny.

This year’s report is available at www.provost.utoronto.ca/English/PerfIndic2005.html. It offers both temporal and inter-university comparisons. The report also includes new information from surveys of the student experience at U of T. While our undergrads give U of T high marks for academic standards, they tend to rate their overall experience below that of some of our peers. In contrast, a majority of students in graduate and professional programs rate diverse aspects of their U of T experience from very good to excellent.

When it comes to performance measurement, as I mentioned earlier, how we’re doing depends on what gets measured. We’ve got good reasons to celebrate our overall “top-of-class” average. But there are some lower grades on our report card, and we’re committed to becoming a “straight-A” institution.

One postscript: In healthcare I quickly learned that some of the most important aspects of institutional performance received the least attention. In universities, indexes of alumni engagement and support are among the measures that are often overlooked. U of T’s alumni as a group must surely rank as our most capable ambassadors, our most effective champions, and our most constructive critics. To all of you, your alma mater owes immeasurable thanks.

As well, during those July celebrations, six porters died while accompanying tourists on treks of K2. The sheer number of hikers and climbers that summer meant inexperienced local men were offered double wages to carry loads, and, with only minimal government regulations on portering, they accepted. The result? Five drowned while taking a shortcut across a glacial stream; another fell, unroped, into a crevasse. Two of the men’s bodies were left on a rock in the Braldu River because authorities would not pay to recover them.

This indifferent attitude led Ken MacDonald, a professor of geography at U of T Scarborough, to start Khurpa Care: an organization that educates trekkers about the injustices porters face, and also teaches porters about medical concerns, such as high-altitude sickness, and their rights as labourers. MacDonald has spent almost 20 years off and on in Pakistan, many of them in academic study of the plight of porters. As a master’s student pursuing glaciological fieldwork in the late 1980s, he lived in villages in the Karakoram Mountains of northern Pakistan, and observed the disparity between the porters’ conditions and those of the trekkers. After completing his PhD, he began investigating the political economy of labour relations in mountaineering and high-altitude trekking.

The average North American likely wouldn’t consider scaling an inch of the 28,250-foot glacial mountain without four-season tents, Gore-Tex jackets, proper trekking boots and a variety of other mountain equipment. But porters are often outfitted in cheap rubber shoes, polyester sweaters, used jackets and small plastic sheets that serve as raincoats. At night (in temperatures that plummet to –25 C) up to a dozen porters sleep under a single tarp. They are sometimes required to carry boxes of supplies weighing up to 35 kilograms on wooden frames strapped to their backs with ropes. If porters are struck with high-altitude sickness, some guides will force them to continue the trek under threat of lost wages. The poor working con­ditions lead to serious health problems for porters, including respiratory infections, neurological damage and arthritis. Deaths occur regularly.

The main reason for this abuse is the rise of the “middleman,” or subcon­tractor, within the travel industry, says MacDonald. Fifty years ago, mountaineers and trekkers would hire porters upon reaching Karakoram; now they often book their trips through a North American company, which subcontracts labour arrangements to a Pakistani firm. Many of these brokers in both North America and Pakistan have the sole aim of producing profit – resulting in what MacDonald calls “outdoor sweatshops” for porters. “In many ways, it’s a fascinating structure of ignorance. A lot of these North American firms do no monitoring whatsoever,” he says. “They’re basically using structures of labour that we would put people in jail for here if they contributed to labour deaths the way that these companies are contributing to labour deaths.”

Travellers also reinforce the inequal treatment of porters because they may view them as “other” or the differences as “natural,” says MacDonald. This perspective has its roots in colonialism, he says, citing the writings of a french mountaineer who climbed K2 in 1938: “Their misery was terrible to behold, but they did not appear to feel this in the slightest. It seemed to fit them naturally, as naturally as the rags in which they were clothed.” MacDonald then quotes a British mountaineer he interviewed in Karakoram in 2001: “I think it’s fair to say that they are different. That they are better able, for whatever reason, physically or mentally, to handle pain than we are. They are able to cross 6,000-metre mountain passes in flip-flops when we wouldn’t even think of trying.”

“When they’re saying they’re physically different or mentally different, they’re attempting to say, ‘They’re tougher, we’re weaker, they don’t need the protection we need’ – which is nonsense,” says MacDonald.

In order to put a stop to the exploitation of porters, mountaineers and trekkers need to ensure the porters have ade-quate equipment and food before the trip begins, and oversee the guides to ensure that the porters receive full payment, says MacDonald. If porters come down with high-altitude sickness, trekkers need to see that these men get paid regardless. “You are the ultimate employer, even though you’re giving money to a company who is arranging things,” says MacDonald.

He adds: “This has to be emphasized: nobody wants [portering] to stop. There is a lot of promise in this form of tourism and the economic benefits it could provide. But what people at the low end of the scale want is more equitable distribution of the benefits – and that’s not what’s happening now.”

Lambeosaur

David Evans, a PhD student in zoology at the University of Toronto at Mississauga, reconstructed the brain and nasal cavity of the lambeosaur using fragments of fossil bone, and determined that the system responsible for the sense of smell did not change drastically in lambeosaur evolution. He also confirmed that it is unlikely that the crests evolved primarily to heighten sensitivity to smells. These findings add weight to two popular theories: that the complex nasal passages inside the crests were used to create honking noises to attract mates or warn of predators, and that the crests were used for visual display in mate selection or species recognition.

Kurtz’s story is retold in a graphic-novel format with text by Timothy Stock, a PhD student and philosophy lecturer at the University of Toronto, and graphics by illustrator Warren Heise, in the latest issue of Alphabet City. The ideas-oriented periodical, edited by John Knechtel (BA 1987 UC), explores the politics of suspicion in a post-9/11 world through a collection of photography, essays, film stills and fiction. In his introduction to the issue, Knechtel asks: “How does one forgive for being made to fear? What is the appropriate response to the suspect? Can anyone feel secure after terror?” The questions surrounding suspicion are examined in an essay from U of T philosophy professor Mark Kingwell (BA 1985 St. Mike’s), fiction from Jack McClelland writer-in-residence Camilla Gibb (BA 1991 UC), and photography by alumna Rita Leistner (BA 1988 Woods, MA 1990) and others works – raising new responses to the intertwined world of those doing the suspecting and those being suspected.