Freedman met a young student suffering terribly with multiple sclerosis. 'Do something for this damn disease,' the man pleaded. Today, the neurologist is a leading authority on MS research.
August 19, 2002 Monday
The Ottawa Citizen
Mark Freedman is a tall and burly man, a six-foot-two, 240-pound doctor-scientist intent on making life better for people with multiple sclerosis. Yet even he wonders whether he could ever endure what he puts his patients through.
The Ottawa Hospital neurologist is co-leader of a major trial being closely watched by scientists around the world: highly experimental and risky bone marrow transplants to try to effectively give people with MS a new immune system and stop progression of their debilitating disease.
The study, a Canadian first, involves eradicating a person's own immune system with high-dose chemotherapy, then rescuing the patient with stem cells isolated and collected from their blood. The hope is that the stem cells will generate new immune cells that won't attack myelin, the insulating lining that wraps around nerves in the brain and spinal cord. In MS, the patient's immune system, led by cells called T cells, launches a misguided attack against myelin, gradually and irreversibly destroying it. Of six patients treated so far, MRI brain scans and other tests reveal "absolutely no enhancement" of the disease's activity, Dr. Freedman reports. In other words, no new brain lesions or any worsening of plaques that existed pre-transplant.
"And these were people who used to light up like a Christmas tree when we injected them with dye," the 47-year-old doctor says. "So we've shut down the enhancement, and this as long as a year" after the first patient was transplanted.
But Dr. Freedman, who knows the risks of overselling science, is quick to stress that the results so far could simply be a reflection of the "heavy duty chemo," and nothing to do with the stem cells themselves. Over the years there have been reports of patients discovering their rheumatoid arthritis went into remission after they developed cancer and had a bone marrow transplant; similar spontaneous remissions have been reported in people with MS. Moreover, before their transplant, the Ottawa patients were "up and down" all the time.
Even if the transplants prove successful, "so that we've got a whole new set of T cells and a whole new immune system that reacts differently and these patients are now free of disease," Dr. Freedman says, will the researchers know exactly what changes have taken place? And will it be possible to induce those changes in a patient without having to put them through a procedure that could kill them?
All are questions the Ottawa doctor is pursuing with the same single-minded determination that kept his accountant father up at night, poring over columns of numbers; his father is still working today, at age 86. "You start a project, you finish it, and you get your answer. That's what my father taught me." But the transplants are only part of the story: Dr. Freedman, for now, is director of the Ottawa Hospital's Multiple Sclerosis Clinic, one of the largest MS clinics in the country. When he arrived in 1993 from Montreal's McGill University, there were 300 patients; today, there are 3,000.
He is in such high demand on the medical circuit that his wife jokes he doesn't stay in Canada long enough to qualify for landed immigrant status. There's a suitcase by his desk during a recent visit. "Boston this weekend," he tells me.
He has been home only two weekends since April. Each of the coloured files in the folder that squats on his desk is another city, another meeting: Alabama, Chicago, Denver, Frankfurt, New York, Houston. Even when he's home, he rarely makes it through the door before 8 p.m.
The three children whose old crayon drawings are tacked up high on the wall in his sixth-floor office are "kind of used to me not being there," their father says. After a pause, he adds, "I'm away from home probably more than I should be."
But the man who was once convinced he didn't have the grades to even make it into medical school is now being aggressively pursued by one of the most prestigious universities in North America. Dr. Freedman has had job offers before; last year, he turned down Stanford. This time, frustrated by what he describes as "nose-diving" morale fuelled by hospital restructuring, he is seriously considering an offer to head two MS programs at Yale University in the U.S.
If he leaves, the city will lose a physician who is contributing crucial new insights into MS, a condition that for years was the classic "one textbook" disease. Little was known, even less was written about it, and the only way doctors diagnosed MS was by excluding everything else. In other words, "if you don't know what else to call it, it's probably MS," Dr. Freedman remembers being taught while training as a neurologist in Toronto, his native city.
"We used to just tell patients, 'You have some inflammation in your nervous system. There, there, we'll see you later.' You couldn't do anything. There were no drugs, no treatments. It was only after the disease sort of raged for a while and people started getting other deficits" that doctors intervened. "So if you couldn't hobble, you'd get a cane, or a brace. If you couldn't urinate properly, we'd give you a drug for that, or put in a catheter.
"People said, 'Why are you doing this? Why are you going into such a field where the patients are so pathetic, there's nothing you can do for them?' And I said, 'That's just it. There's got to be something we can do for them, it's just that nobody's looking."
Today, there are four approved therapies that help reduce the number of MS attacks, and the advent of MRI has revolutionized the diagnosis, allowing doctors to spot MS sooner and start treatment earlier, "because the more attacks patients have up front in the first few years, the faster they progress," Dr. Freedman says. And, far from pathetic, he has worked with patients fiercely determined to not let the unpredictable and insidious disease control their lives. The patients volunteering for the bone marrow experiments he has "all the respect for in the world."
"This is a gutsy move. For them to be able to come through it and say, 'Oh, it wasn't so bad.' My God, it looked awful. I don't know that I would have what they have."
What he has, say those who know him, is a deep understanding of patients and how the disease affects them, and an uncanny ability to relate to people. Ask people to describe him and the words used most are high-energy, outgoing, highly driven. The man who played rhythm guitar in garage bands in high school and who was never really "turned on" by school now has an international reputation as a teacher who is as comfortable addressing a roomful of brain doctors as first-year med students.
As a boy, he drove adults nuts with his endless questions. Like all good scientists, that insatiable curiosity remains.
"If you talk to many doctors who are involved in treating people with multiple sclerosis, they may tell you the names of all the drugs that we use, in the same way Mark can tell you that, but if you pushed a little harder and said, 'Well, how do you think they really work?" that's where Mark stands a step above the others," says Dr. Jack Antel, a leading neurologist at McGill University who is working on ways to turn the body's own cells into a repair crew to fix the damage caused by MS.
"Mark continues to think, why does something work, why doesn't it work, what should we do next?"
If he were in school today, he probably would have been labelled with attention-deficit disorder. Mark Freedman could never settle down, mostly because he was bored. "Nothing really turned me on."
But he used to pretend he was a scientist, playing with bugs, and a career in research eventually beckoned.
He was in the process of getting his PhD in molecular neurochemistry at the University of Toronto when his supervisor, frustrated at not being able to get grant money "while all those damn doctors seem to be getting all the money" told Dr. Freedman he should try getting into medical school.
"I said, 'You've got to be kidding.' But I thought, if I could do that and get back to research some day, and that gives me a portal to getting more research money, I'll do it."
He applied to medical schools fully expecting to be turned down based on his transcripts alone. "Then boom, I got into the U of T. And I went, 'what do I do now?' "
After graduating from medical school in 1983, he travelled to the renowned National Hospital in Queen Square, London, England, the place where Hughlings Jackson, the "father of English neurology" worked and studied, "and I'm meeting the characters I'm reading about in my Principles in Neurology book." Dr. Freedman was hooked.
"The heart's just a pump, the kidney's just a filter. What's the organ I'm going to go after? Where is there the most unknown? I came back to Canada and was convinced I wanted to do neurology."
But he had no idea what field -- stroke? Parkinson's? -- until a chance encounter with a young MS patient while he was chief resident at St. Michael's Hospital in Toronto.
"They brought in this young guy with MS to treat with cyclophosphamide, which was a terrible chemotherapy drug that was being tried in those days to treat anything auto-immune that wasn't responding to standard treatment," Dr. Freedman recalls.
He walked into the patient's room and felt something in his stomach give. "It was someone I knew from grad school. I said to him, 'I never knew. When did you have MS?' And he said that the symptoms probably started back in school. And now he's paralysed. He can't run his bladder; he's going down the tubes. We talked for about an hour. I told him I was thinking about doing research, but what field, I didn't know. Finally he said, 'Look at me. Do something for this damn disease. They haven't found anything for this disease.' He left me with that: Cross this line. So I took it at that. I guess I was emotionally charged to do something."
At that time, MS was the black hole in neurology. Even though it had been identified almost 130 years earlier, doctors still did not know what caused it, or even if MS was a single disease, or multiple diseases.
According to the Multiple Sclerosis Society of Canada, Canadians have one of the highest rates of the disease in the world. Every day, three more people in Canada are diagnosed with MS. The disease, which often strikes in early adulthood and affects twice as many women as men, causes loss of balance, impaired speech, extreme fatigue, double vision and paralysis.
There are two aspects of MS, Dr. Freedman explains. First, the day-to-day "smouldering symptomatology" caused not just by the damage that's already been done, "but to this very active disease in their nervous system they just can't shut off."
"And then, every once in a while, they have these attacks, where there's an escalation of activity, and they can't walk, they can't see, they can't urinate, they are totally imbalanced or so fatigued they can't stand or walk for days at a time." The attacks often require treatment, sometimes with high-dose steroids and hospitalization, "but they eventually get over them."
But the patients in the bone marrow transplant program "were having repeated, repeated episodes like that. And they just weren't coming back to baseline." Rather, they were gaining more and more disability and become increasingly resistant to every medication available. "We had nothing else to offer them."
The study, which is being headed by Dr. Freedman and Dr. Harold Atkins,
a bone marrow transplant doctor at The Ottawa Hospital, and involves a
dozen co-investigators from Ottawa, Montreal and Toronto, uses what is
known as "autologous stem cell transplantation." The gruelling procedure
first involves removing bone marrow from the patient's pelvis, and freezing
it to use as backup, "so that if anything goes wrong, we'll just put them
back the way they were," Dr. Freedman says.
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