The other members of the molecular genetics research team gathered in Robert Korneluk's office didn't know what to make of the lab results passed around one morning in the fall of 1994.

Looking at an analysis of DNA sequences -- they had managed to narrow down their search to 125,000 base pairs from the three billion that compose the human genome -- they noted that a family of genes that regulate the death of cells in the human body looked like a gene that comes from an insect virus. They weren't sure how significant that might be.

Meanwhile, Dr. Korneluk's mind was racing. Since they started nine years earlier, Dr. Korneluk, his partner Dr. Alex Mackenzie, and the rest of the researchers in the Solange Gauthier Karsh laboratory at the Children's Hospital of Eastern Ontario had made one breakthrough after another -- identifying and cloning genes responsible for two degenerative neuromuscular diseases, myotonic dystrophy and spinal muscular atrophy. But this was something else entirely. This one took a leap of imagination, and Dr. Korneluk was the first to make it. Humans share a lot of genetic information with species closest to them: chimpanzees and orangutans, for instance. Something found in both man and insect, Dr. Korneluk said, "had to be there for a reason ... an important reason." The CHEO researchers had not only identified a gene that destroys nerves cells, but they had characterized it, opening the door to gene therapies that could effectively treat these neuro-degenerative disorders and a variety of other diseases, including cancer.

The very prospect, he later said, "hit me like a ton of bricks."

Another research scientist would probably have offered a memorably eloquent line, but Dr. Korneluk is more real-world than ivory tower. His father was a steelworker in Sault Ste. Marie. When he assured his fellow researchers that this was the stuff of a medical breakthrough, it was in language his late father would have understood. "I told them, 'It walks like a duck. It sounds like a duck. It's a duck,'" he said.

He left unsaid something else that he sensed, namely that this was a personal and professional watershed. "Things were going to be different from that point on," he said. "My life and work, theirs, this hospital's, and a whole lot more."
It might sound like Dr. Korneluk was getting ahead of himself. That was hardly the case. Construction will start this fall on a new building at CHEO, the Apoptosis Research Centre, which will focus on the cellular research of Dr. Korneluk and his team. Asked when he first envisioned this complex, he doesn't flinch.

"Truth is, yeah, I kept it to myself, but I did see this happening when we had the results back from the lab that day," Dr. Korneluk said.

Dr. Korneluk also knew that he would have to meld science with business, not for profit so much as for protection. Soon, drafts of business agreements and mergers would take their place on his bookshelves beside his medical texts. "We had to be concerned about 'Big Pharma' (pharmaceutical companies) exploiting the intellectual property and maybe preventing us from doing the science or taking it out of Canada," he said.

In December 1995, Dr. Korneluk and Dr. Mackenzie founded a company, Apoptogen Inc., for those very purposes. A couple of years ago, Apoptogen merged with another biotech company to form AEgera Therapeutics, but the model has stayed essentially the same. As a condition of the merger, Dr. Korneluk and Dr. Mackenzie received a guarantee of the continued participation of CHEO and the University of Ottawa, where Dr. Korneluk is a professor of microbiology, immunology and biochemistry.

"Some people are critical that the institute is involved but, the fact is, what's good for the business is good for the founders, and in turn what's good for the business is also good for the institute," Dr. Korneluk said.

Many people who have never worked in a medical research laboratory have preconceived notions about those who do. They presume that researchers are lab coat-wearing A students who spend their lives on the lab benches, squinting into microscopes, peering into beakers, living in a vacuum, a scientific and academic shelter from harsh reality.

Dr. Korneluk, who holds a PhD in developmental biology, is proof of how wrong-minded that ascetic stereotype is.

"When my wife heard I was going to talk to a reporter, she asked me as a joke if I was going to wear a lab coat," said Dr. Korneluk, who sported his usual office wear, jeans and a short-sleeved shirt with a vaguely tropical print. "It's either this or a golf shirt if I'm getting in a round with one of the researchers."

"Bob makes the atmosphere so light," said Sandra Hurley, one of the lab technicians. "He values good work, but he doesn't think that you can't do good work in a relaxed environment."

For a scientist who has been honoured by the Governor General and recognized by the Howard Hughes Medical Institute, he is painfully plain-spoken and impossibly self-deprecating.

Ask him about his university days and he'll say that he was motivated most by his father or, moreover, by fear that he might end up working beside him in the steel mill. "He would work an eight-hour day at Algoma and then work another eight hours afterward," he said. "He literally built an apartment building by himself. A church, too.

"When I was a kid, when my friends were heading off to play hockey, I'd be pouring cement for him or straightening out nails he'd salvaged. I worked five summers at Algoma -- had to stuff myself with bananas and water to get up to the 140-pound weight minimum to get hired. For me, no matter what I did in school, there was no dropping out and going back."

Ask him what his strengths are and he'll rhyme off personal shortcomings. "I bring insight to the table, but I'm not terribly bright about things and I might not appear to be terribly dedicated."

Ask about his post-doctoral work at the Hospital for Sick Children in Toronto back in the early 1980s and he'll profess to being in over his head. "I was coming over from biology. I wrote my thesis on newts. I looked around and for six months I didn't know what hit me."

"Bob isn't caught up in sophistry and he does make this a fun place to work, what with making jokes or organizing the staff hockey games, but don't mistake that for a lack of seriousness," Dr. Mackenzie said. "He's also incredibly intuitive. He has a great nose for important science."

Though Dr. Korneluk seems almost incapable of taking himself seriously, he is almost evangelical in his belief that the theme of his team's genetic research, apoptosis (programmed cell death), could revolutionize medicine. "My friends and even my wife are always telling me how much I go on about it, and they accuse me of being the Archbishop of Apoptosis."

Until the 1970s, little research had been dedicated to the death of cells, presumably because of their perceived abundance: 100,000,000,000,000 (one hundred thousand billion) cells in the human body. Scientists knew that cells were sometimes killed off by external forces, necrosis, a sort of cell murder. Otherwise, it wasn't a hotly pursued line of research.

In 1972, opinion about cell death took a radical turn, thanks to the work of three scientists at the University of Aberdeen in Scotland. They determined that cells are actually programmed to die -- in fact to kill themselves -- a process frequently described as "cell suicide."

Though this is a vivid and accurate metaphor for the layman, apoptosis is the term that appears in scientific journals. Though it doesn't quite roll off the tongue, its origins are colourful: Andrew Wylie, one of the co-discoverers, consulted friends in the university's classics department and borrowed a word from a Homeric poem, Greek for "the fall of the autumn leaves."

One gene in every cell, TP53, is programmed to destroy the cell to protect the body against infection, disease and trauma. "Only in the last 10 years have scientists been able to appreciate how relevant these findings might be," Dr. Korneluk said.

Understanding the genetic underpinnings of apoptosis might be crucial to combatting diseases affecting the central nervous system because, unlike other cells in the body, nerve cells never divide, and thus when they die they are not replaced. If researchers could find a way to regulate the apoptotic gene, they might possess the key to treatment of degenerative diseases such as dystrophies, Parkinson's, Lou Gehrig's and even Alzheimer's.

"In these cases, cells that shouldn't die kill themselves prematurely," Dr. Korneluk said. "And then there's cancer (in which) cells that should die, don't. Cancer cells survive in the middle of a tumour, without oxygen and the other support that a cell should need. They survive the bombardment of radiation and chemotherapy. Find a way to make these cells die when they should and you'd have an effective treatment for cancer."

These days, Dr. Korneluk and his partners in research and business are hunting for IAPs, inhibitors of apoptosis. They have isolated IAPs in rats, and their research has resulted in 15 U.S. patents on IAPs. CHEO and the University of Ottawa own the patents and license them to AEgera. In association with a consortium of researchers in the United States and Europe, they are planning to embark on human trials on IAPs in England later this year.

"Knowing the molecular basis of apoptosis, we can design drugs around it," Dr. Korneluk said. "We're at the point where we're able to make the translational leap, taking our research findings into therapies."

Dr. Korneluk describes Ottawa as "an ideal community for research" but, as he tells it, the origins for CHEO's gene research can be traced to Quebec's Saguenay-Lac-Saint-Jean region.

"When I first came to CHEO as a research assistant, the head of the department, Dr. Alisdair Hunter, made a truly inspired decision," Dr. Korneluk said. "He decided that we should research myotonic muscular dystrophy. He understood that you have to work with whatever you can put to your advantage."

What the CHEO team had in Lac-Saint-Jean was an unusually high concentration of myotonic dystrophy, the most common of the neuromuscular dystrophies. The incidence of myotonic dystrophy in the general population is one case in 8,500.

In Lac-Saint-Jean, the incidence was one in 500, 17 times the normal rate, a circumstance tracing back to the region's founding families and, according to records, to a couple who married in Normandy 300 years ago.

"This was a hugely important lesson that Alisdair gave me," Dr. Korneluk said. "Your research needs to have a connection to the world outside the lab. Because he was connected to the community, and to the clinical work being done, he realized that there was this historically high incidence (of myotonic dystrophy) in Lac-Saint-Jean, something that could be used to our advantage in trying to isolate the gene for the disease."

The gene research at CHEO was not only well-placed but well-timed, benefiting from the breakthrough in molecular science with the Human Genome Project. "It wasn't so long ago that it was hotly debated whether (the reading of genetic code) was even possible," Dr. Korneluk said. "It was an exciting time to be involved in genetics, and with the people in our lab we had developed an expertise in gene-hunting. We had something to build on. We had a good team."
Though Dr. Korneluk and Dr. Mackenzie are the lead players in this research, out in front on the dozens of published articles and on the board at AEgera, they emphasize that their research is a collective effort.

"Bob understands that running a lab is as much an exercise in sociology as it is in science," Dr. Mackenzie said.

"Of all the things that have come out of our work at CHEO, one of the things that I'm proudest of is the fact that we've never had to fire or let go someone that we've brought in to work in our lab," Dr. Korneluk said. "That comes down to reading people and getting a sense of who can work here -- not just who can do the work, but who can fit in and be happy."

Dr. Korneluk admits that he doesn't spend as much time in the lab as he did as a young man, and says simply that it's "somebody else's turn."

As a teenager, when his father didn't need him on a job site, he would steal away to a swamp and gather frogs and other pond life, satisfying the type of curiosity that brought him first into biology and later, somewhat tortuously, into molecular genetics.

These days he doesn't bristle at trying to balance the hard research at CHEO with the demands of AEgera or managing the department. He views talking with the media or lobbying for grants or networking within the medical community as part of the job. He enjoys the perks that go with it. His work has taken him around the world. It has also given him the opportunity to meet some famous figures outside the research community (including the late Yousuf Karsh, one of the largest individual contributors to CHEO's research department).

"The researcher who lives only for the lab work isn't doing justice to the research," Dr. Korneluk said. "We get into this field because we are curious about the science, we want to see how things work. For us, that's the fun part, but it doesn't stop there.

"You have to write the findings and write for grants. You have to teach. You have to manage your research like a business and not go through your funding for a four-year project in 18 months. You have to find people to work with you. The idea of someone working alone in the lab isn't completely a myth, but it's rarely the case.

"With all the other stuff, the business and everything else, there's no chance of forgetting what our research is really about and why you're here -- not when you're walking in CHEO every day and you see the faces of children who have these dystrophies."

The Researchers
The Series: Some of the best and brightest minds in medicine are turning Ottawa into the fastest-growing medical research centre in Canada.

Last Monday: We profiled psychologist Gary Goldfield, a researcher devoted to bettering human health through proper diet and exercise who is driven by this sobering statistic: one in four Canadian children is obese or overweight.

Next Monday: Cancer researcher John Bell, who has a personal connection with a disease that he hopes to eradicate with an experimental virus that kills drug-resistant tumours.

Online: Read previous profiles at canada.com/ottawa/ottawacitizen.