About 18 years ago, Dr. Charles Bernstein returned to Winnipeg with some new ideas about how to help people who suffer from Crohn's disease and colitis. Today, he heads a program that has quietly become a world leader of research into inflammatory bowel disease.
BY JOEL SCHLESINGER
Winnipeg Health Region
Wave, March / April 2011
It was the fall of 1988,
and John Harvie was
entering the prime of life.
The 28-year-old Winnipeg man was
in excellent physical condition, married
with a young family, and embarking on
a promising career with the Canadian
Forces as an airframe technician.
And then his dream life slowly started
to slip away. First, he lost his appetite.
Then he started to lose weight because he
couldn't keep a meal down. As his health
deteriorated, he started to experience
excruciating stomach pain, diarrhea and incontinence. It was not a pretty sight,
recalls Harvie. "I was literally projectile
Eventually, Harvie was diagnosed with
Crohn's disease, a form of inflammatory
bowel disease (IBD). The condition causes
the body's immune system to go into
overdrive, attacking the otherwise healthy
lining of the digestive tract. The disease
left parts of his colon, small intestine and
rectum inflamed and covered with ulcers.
Harvie would spend the next few years
struggling against the condition, but for
the most part his illness would have the
upper hand. "I had really debilitating
pain - ongoing, endless pain. I went from
a healthy 180-pound man down to 119
Physically unable to meet the
demanding requirements of his job with
the Armed Forces, Harvie was placed on
long-term disability. Simply put, Crohn's
was stealing the best years of his life.
By 1994, frustrated, tired and losing
hope, Harvie landed in the care of Dr.
Charles Bernstein. At the time, Bernstein
was just settling in as the head of the
newly created Inflammatory Bowel
Disease Clinical and Research Centre in
the Faculty of Medicine at the University
of Manitoba's Bannatyne Campus. A
year earlier, Bernstein, who had been
a professor at UCLA in Los Angeles,
had returned to Manitoba to head up
development of the Faculty of Medicine's
academic gastroenterology program.
Harvie could not have known it back
then, but that first meeting with Bernstein
would mark the beginning of a remarkable
journey, one that would ultimately change
his life for the better.
Although he was barely out of training,
Bernstein had some new ideas about how
to help people like Harvie. Under his
leadership, the IBD Clinical and Research
Centre would soon become a world leader
in the investigation and management of
inflammatory bowel disease, which is a term generally used to describe Crohn's and ulcerative
colitis. That work would translate into leading-edge
treatments for IBD, treatments that would help Harvie
and others like him gain control over their conditions.
Today, the man who once couldn't leave his house
for days at a time because he was too weak to get out
of bed has reclaimed his life. With the symptoms of
his disease largely in check for several years, Harvie,
now 56, is finishing up a degree and leading a normal
life, working as a vocation rehabilitation facilitator.
And, he says, he owes it all to Bernstein and his
team at the IBD clinic. "I'm really lucky in a lot
of respects that I live in Winnipeg," he says. "He
(Bernstein) has basically given me my life back. I have
a far better quality of life. That's not to say that I don't
have a disability or there aren't some challenges, but
they're much easier to accept."
Winnipeg did not become an international leader in
IBD research overnight.
That process can be traced back to when Bernstein
decided to continue his postgraduate training in Los
Angeles. Initially, he thought he might specialize
in liver disease. "When I went to UCLA to train,
I thought I might actually become a liver doctor,
but while I was there, they had a big IBD research
program," Bernstein says.
By the early 1990s, he had completed his fellowship
in gastroenterology. With a special interest in IBD
and intestinal transplantation, he joined the Faculty of
Medicine at UCLA.
He could have easily remained there and raised
his family in Los Angeles with a comfortable, tenured
career at the school as a specialist at one of the
world's leading health-care centres.
But in 1993, Bernstein chose to return home to
Winnipeg with his wife, Evelyn, to
raise their two children, Matthew
and Lexie, close to the rest of their
family. His old hometown also
offered something else: a chance
to build a research and training
program within the Section of
Gastroenterology at the University
of Manitoba's Faculty of Medicine. The
IBD Clinic and Research Centre, located on the
eighth floor of the John Buhler Research Centre
at the U of M's Bannatyne Campus, was created
When Bernstein returned to Manitoba,
gastroenterologists moving to the province were
few and far between. "The last gastroenterologist
to initiate a practice in Manitoba before me was in
1977," he says. In other words, there were thousands
of Manitobans suffering from gastroenterological
problems, the number of new cases of IBD was on the
rise, and there was a dearth of expert care.
One of Bernstein's roles was to help develop the
next generation of gastroenterologists in Manitoba,
and by 1995, the Gastroenterology Fellowship
Training Program at the U of M was up and running.
About 7,500 Manitobans have IBD. The condition
is considered to be an autoimmune disorder (a
condition that occurs when the body's immune system
overreacts to substances and tissues normally present in the body) similar to rheumatoid arthritis
or multiple sclerosis. But instead of attacking
healthy joints, as is the case with arthritis,
or the central nervous system in the case of
MS, IBD attacks the digestive system.
When Bernstein was completing his
fellowship in gastroenterology at UCLA 20
years ago, research into IBD had largely
focused on looking at the immune system's
response and how it caused IBD symptoms.
The treatment focus was on dampening the
response of the immune system.
But Bernstein planned to investigate the
disease from a different perspective. "I
thought we'd start by understanding what
the population was who had IBD and work
backward towards the individual from the
Bernstein wanted to understand what
researchers call the "burden" of IBD in
Manitoba. Data on how many people had
it, what groups of people tended to get
it, and trends in disease presentation and
progression could ultimately lead to better
As it turned out, Bernstein embarked on
his ambitious goals at the right place at
the right time. Dr. James Blanchard - a
globally renowned epidemiologist - was
leading the province's Epidemiology Unit
at the time.
"I knew that we had tools in Manitoba
that were quite unique through the
administrative databases of Manitoba
Health where every Manitoban has a
unique personal health identification
number so we could track their
individual medical histories,"
Using the province's
data, Bernstein worked
with Blanchard to
develop the University
Database. In doing so, they created the largest validated
population database for IBD in North
America, and one of only two on the
continent (the other is at Mayo Clinic).
"This served as a fulcrum for
developing our University of Manitoba
Inflammatory Bowel Disease Clinical
and Research Centre here at the Health
Sciences Centre," says Bernstein.
One of the major benefits of having
these data at their fingertips was they
could see the breadth of the disease
amongst the population. "A main aspect
of our research has been to define the
epidemiology of inflammatory bowel
disease locally, which means defining
the burden of the disease, what type of
people get this disease and how that's
changed over time," he says. "We've
been able to take the administrative
definition of IBD we developed and apply
it to databases elsewhere in the country
to define the burden of disease across
the country and show that Canada has
amongst the highest rates of IBD in the
The database was the foundation for
much of the research into IBD that would
follow at the Centre for the better part
of the next two decades. Bernstein and his team were able to look at who had
the disease and identify what form of
the disease they had. They could see
when people were first presenting to the
health-care system with symptoms, and
they could also determine what type of
other medical problems patients with
IBD suffered from and how they were
different than the general population.
Furthermore, they could determine what
type of treatment people were receiving
and, to some extent, the effectiveness of
Most importantly, the epidemiological
information provided IBD researchers
with a bird's-eye perspective of the
illness. They could step back and
observe that IBD was an auto-immune
disease affecting about 500 people for every 100,000. They could also see that
IBD rates were on the rise over the last
five decades of the 20th century in the
developed world, but much less prevalent
in the developing world.
Beyond epidemiological studies,
Bernstein and his team have initiated
studies to explore potential causes of IBD,
so that ultimately cures could be found.
Their work has been highly cited and has
had a major impact all over the world.
Simultaneously, Bernstein started a
clinical trials program. "This provided
Manitobans with IBD who were failing
conventional therapy access to novel
therapies," he says.
Bernstein says genetics play a large
role in the causes of IBD. Some people
are simply more prone to developing
the disease. But as Bernstein and his colleagues continued to build upon
epidemiological research, they also
concluded that something in the
environment was also playing a critical
One of the first indications of this
reality came from studying first-generation
Canadians whose parents immigrated to
Canada from regions of low incidence.
Children of these immigrants fell ill with
IBD at the same rates as the rest of the
Canadian population. Further, in the past
15 years IBD rates have been rising in the
developing world - Asia, Africa and South
America - too.
"So it begs the question: What has
changed?" he says. "One hypothesis
is that it is diet. That in the developing
world, diets have become more westernized."
But demonstrating that rates were rising
as a result of changes in our diet was one
thing. Using that knowledge to pursue
more effective treatments, and even
possibly a cure, was another.
From the start, research into IBD at the
centre branched out from epidemiological
studies - understanding who had the
disease - into many different fields of
study. Clinical research, which aims to
improve treatments, develop new drug
therapies and promote overall care, has
been especially important.
For Bernstein, that has meant working
closely with patients. He estimates he
spends about 60 per cent of his time
in clinical practice. "Seeing patients
provides us with research questions," he
says. "It's also a connection to what's important to them and important in
managing their disease."
But at the centre, they have also
expanded their scope of study beyond
the medical community to look at the
possible environmental causes of IBD.
Bernstein has worked closely with
Dr. Denis Krause, a professor in the
Department of Agricultural Sciences
at the U of M's Fort Garry campus, to
investigate a possible environmental link
between animal farming practices, food
and water contamination with novel
species of E. coli and other bacteria and
"Currently, a leading potential cause of
IBD is that patients who are genetically
predisposed to getting the disease react
to something that is present within the bowel flora," Bernstein says.
The bowel flora refers to the ecosystem
of bacteria that live within a bowel. These
bacteria live within our digestive tract and
help digest food, releasing nutrients that
can be absorbed in the intestine.
The human gut contains billions upon
billions of bacteria. "In fact, there are
more bugs in our bowel than cells in our
entire body," Bernstein says.
But he and Krause have determined
that a certain type of E. coli is present
in the gut of people who have IBD, a
discovery supported by similar findings
in seven other research labs around the
Many different strains of E. coli live
within the digestive tract of different
species of mammals and, in turn, are
beneficial to the existence of those creatures. But some strains can be
harmful. "Enterotoxigenic E. coli are a
strain of E. coli that doesn't invade the
cells in the gut, but instead releases a
toxin," Bernstein says. "Those are the
ones we think of when we go to Mexico
and get turista (traveller's diarrhea)."
Other strains - like 0157:H7 - do
invade the gut's lining and cause a
hemorrhagic illness. "That is the E. coli
of the outbreak in Walkerton, Ontario
- that invades the gut and causes direct
ulceration, and people get colitis and
really sick," he says.
But IBD research here in Winnipeg and
confirmed in other research centres found
that both Crohn's disease and ulcerative
colitis sufferers have an adherent-invasive
strain of E. coli in their digestive tracts.
"We don't know that the E. coli is
releasing any toxins, but we do know
that it can stick to the gut and invade the
epithelial (surface) cells so that's why
it's been given this moniker of adherentinvasive."
Bernstein says a case control study
found the bacteria were present in both
people with IBD and those without. But
the remarkable thing about the study is
that it revealed that this strain of E. coli
was present at greater rates and in greater
quantities in individuals with IBD.
Bernstein says it's still too early to
tell if this is the breakthrough discovery
that will unlock the cause of IBD and
ultimately lead to a cure, but it's an
important first step; an important model
of exploring the bowel flora of affected
individuals. "In essence, it has unlocked a
door that will advance our understanding
of the human bowel providing the
possible environmental link to this
disease," says Bernstein.
This microscopic evidence - while
potentially groundbreaking - is just one
among many clues that Bernstein and
other researchers are pursuing.
Research at the Centre approaches
IBD from many different angles, bringing
together experts from several medical
and scientific disciplines. The more ways
they can approach IBD from a research
perspective, the more likely they'll be
able to see "the big picture" and be
able to put all the different key pieces of
And each piece is important. Consider
the work Bernstein is doing with Dr. Hani
El-Gabalawy, an auto-immune diseases
specialist. They are investigating why First
Nations populations in Manitoba, who
have high rates of gastroenterological
problems and rheumatoid arthritis, have
very low rates of IBD.
"Even though First Nations people
get lots of GI symptoms, they don't get
IBD, so they may hold a clue," Bernstein
says. "It's as important to study a group
that doesn't get IBD to understand the
underpinnings of IBD as it is to study the
group that does."
Other researchers at the Centre are
studying the psycho-social component
of the disease. Lesley Graff and John
Walker, for example, are clinical health
psychologists who have been involved
in exploring the psycho-social aspects of
gastrointestinal diseases, especially IBD.
Bernstein says that many sufferers of
IBD, Harvie included, find that anxiety
surrounding certain symptoms of the
disease, such as incontinence, can make
symptoms of the disease worse. Their
research has shown that stress is associated
with a flare of symptoms of IBD.
Bernstein says the research at the
Centre, while expansive in scope, is all
largely based on that epidemiological database developed nearly two decades
ago. It is the framework from which
all clinical investigations have flowed,
leading to many groundbreaking
discoveries, such as identifying the new
E. coli strain. In turn, these findings have
helped put the Centre - and Winnipeg
- on the map in the global medical
And, in many instances, Bernstein has
been the face of this collective research,
representing the Centre, and appointed to
leading positions at academic and clinical
research organizations around the world.
He is the current Scientific Secretary
of the International Organization for the
Study of Inflammatory Bowel Disease
(IOIBD), which is an organization of 61 of
the leading IBD investigators around the
world. "Two years ago, we completed the
University of Manitoba Bingham Chair
in Gastroenterology," he says. "This is
an endowment, and I am the inaugural
Bingham Chair holder."
These appointments and accreditations
do not simply represent widespread
recognition by the medical
community. They have also
led to increased access to
research funding. "The
Bingham chair meant we
had the funds to recruit
Dr. Jean Eric Ghia, whose expertise is
in studying the connection between the
brain and the gut," says Bernstein.
While the Centre's prominence is no
doubt a consequence of the good work
being done here in Winnipeg, probably
the biggest beneficiaries of all the
research are the thousands of Manitobans
suffering with IBD. Over the years, they
have benefitted from enhanced care,
including the opportunity to participate
in the several drug trials carried out at the
Bernstein says patients at the
Centre have been involved in the
"seminal clinical trials" of both
Remicade (infliximab) and Humira
(adalimumab). These are among the latest
pharmaceuticals currently available to
patients suffering from a range of autoimmune
disorders, including IBD. They
belong to a class of drugs that cause the
immune system to "down-regulate" or
diminish its response to what it perceives
as a threat to the body. This in turn
alleviates the symptoms of diseases
like IBD, which are largely caused
by the immune system attacking
healthy tissues in the body.
Harvie was one of the
patients to benefit from
participating in a drug trial at
the centre. "John was enrolled in one of
these early Humira trials," Bernstein says.
"Not everyone responds to these drugs,
but John responded very well and has
remained on the drug after the study was
completed and became available to the
Harvie says he had been involved
in many trials at the centre, so many
that Bernstein had often jokingly and
endearingly referred to Harvie as his
"professional study patient."
But Humira turned out to be the most
successful. "My recovery has really been
quite incredible," says Harvie.
Today, about 95 per cent of IBD
sufferers can effectively manage their
condition and lead full and productive
lives. Still, Bernstein says drug therapies
alleviating symptoms represent only
one victory on the road to winning the
war: finding the cure. "These are drugs
that can cost $30,000 to $40,000 a year
in any one individual, and in any one
individual who is successfully treated
with them, they often stay on these drugs
for years," he says. "So, there are lots of
But up until research began at the
Centre in the early 90s, a main effective
treatment for IBD was surgery, removing
the affected piece of the digestive tract. The procedure worked well for
ulcerative colitis sufferers because their
disease was localized to the colon.
"Obby Khan, the centre for the
(Winnipeg) Blue Bombers, has promoted
the notion that you can have a regular life
with this, even more than a regular life"
Bernstein says about Khan, who has been
a patient of his after having such surgery.
"He went back to playing professional
football afterward, so you can live a
normal life afterward."
But for Crohn's disease sufferers who
may have disease in their small bowel and
colon, surgery - while effective in some
instances - may be a slippery slope.
"We're a little bit more circumspect
about it because we're concerned that if
we operate, the disease will occur again,
and two, three or five years, we're back to
square one, and we can't keep cutting."
Drug therapies hold the most hope for
Crohn's sufferers like Harvie, who had
part of his bowel removed before coming
under the care of Bernstein. Yet a cure for
IBD may not be that far away, Bernstein
says, believing the mysteries of IBD will be
unravelled in his lifetime. "I don't know if
our group will be the ones to figure it out,
but it will be figured out," he says.
Ultimately, he suspects it's likely there
may be multiple causes to what may turn
out to be multiple diseases. Yet, it is just as
likely that one key discovery will unlock
the secrets, much like in the case of peptic
ulcers. They were once believed to be
caused by over-production of stomach acid
from stress and diet, until two Australian
scientists discovered in the 1980s a type
of bacteria, was the cause of these ulcers
in up to 90 per cent of all cases. "When I
was at UCLA, then a "mecca" for studying
peptic ulcer disease, this organism -
Helicobacter pylori - was just discovered
and it changed the way we manage peptic
ulcer disease," he says. "That is the Holy
Grail: We're looking for that Helicobacter
pylori equivalent in IBD."
Joel Schlesinger is a Winnipeg writer
Wave is published six times a year by the Winnipeg Health Region in cooperation with the Winnipeg Free Press. It is available at newsstands, hospitals and clinics throughout Winnipeg, as well as McNally Robinson Books.
Read the March / April 2011 issue of Wave