Melanie Fridl Ross
Atkinson is a big-picture guy in a small-picture world.
Over the last 17 years, Atkinson has forged a reputation as
one of the world’s leading diabetes experts by conducting
innovative basic research on the physiological changes that
cause the debilitating disease.
the same time, Atkinson has sought to pull back and understand
how advances in his field and in related fields can be most
effectively employed to serve patients and their families.
I Diabetes – An Autoimmune Attack
1: Insulin-dependent or “type 1”
diabetes occurs when white blood cells vital to the body’s
defenses against infectious diseases launch a self-directed
or “autoimmune” attack on insulin-producing
beta cells in the pancreas. The insulin these beta cells
produce regulates how the body uses and stores sugar and
other food nutrients for energy.
2 or non-insulin-dependent diabetes differs from its type
1 cousin in that it usually occurs in overweight individuals
who typically fail to exercise regularly. These people
develop a resistance to insulin, leading to symptoms of
the disease. They account for 90 percent of the nation’s
estimated 17 million diabetics.
“Pathologists are thought by many to be individuals
who focus on details. They hang around the microscope and
try to look at smaller and smaller images,” Atkinson
says. “While there’s a time for doing that, there
are also times when it’s better to take a step back
and look at the whole picture.”
It’s a view that’s not always shared by some of
his basic science brethren, many of whom have chosen a life
in the lab over a clinical career with its customary contact
But Atkinson, 43, has been heralded for his ability to bridge
research interests with a commitment to directly serve patients
and their families. He leads tours of his lab. He answers
dozens of e-mails from people desperate for a cure. He gives
generously of his time to national organizations such as the
American Diabetes Association and the Juvenile Diabetes Research
Foundation, regularly updating physicians and the public about
the latest research developments.
In fact, the ADA recently honored Atkinson with its 2004 Outstanding
Scientific Achievement Award, sponsored by Eli Lilly and Company,
calling him “one of the rare individuals who sees the
big picture, from genetics and DNA to bench-side and clinical
application. He has helped the cause of diabetes at many levels,
working with equal passion in research, patient advocacy and
in raising diabetes awareness.”
The honor, presented at the ADA’s annual meeting on
June 8th in Orlando, is given to a scientist who has conducted
outstanding research in diabetes and for creativity of thought.
Four days later, Atkinson was in Washington to receive the
Mary Tyler Moore and S. Robert Levine, M.D., Excellence in
Clinical Research Award, given by the Juvenile Diabetes Research
Foundation International for contributions to the clinical
translation of diabetes research.
“We’ve been trying to identify Ph.D. investigators
who epitomize the translation of research to the bedside,
and Mark exemplifies this beautifully; he is highly deserving
of this award,” says physician Richard Insel, JDRF’s
executive vice president of research. “Mark has that
unique ability to immediately think about the translation
of basic science research, and he keeps his eyes on the big
picture. I think he exemplifies exactly what you’d want
to see in a Ph.D. who is conducting biomedical research. He
goes beyond the day-to-day basic science results and thinks
about the clinical applications. He’s always focused
on how he can apply his biomedical research to the bedside.”
Ask Atkinson how he views his role, and he boils it down like
this: Find what causes diabetes, predict who is at risk, then
prevent the disease altogether.
Sometimes insights into how to achieve those lofty goals come
from unexpected places.
Three miles outside Bar Harbor, Maine, the Jackson Laboratory,
the world’s largest mammalian genetic research facility,
breeds more than 150 strains of mice for diabetes and obesity
research. But it’s one in particular that has Atkinson
Last spring, in a colony of non-obese diabetic mice, Jackson
researchers who routinely collaborate with Atkinson noticed
something unusual, a true quirk of nature. The mice were supposed
to be of normal weight and develop type 1 diabetes. But a
single mouse was born that grew downright plump. Not only
was the animal obese, it developed type 2 diabetes, not type
1 like its littermates.
Centers for Disease Control and Prevention recently reported
that one in every three children born in 2000 will eventually
develop diabetes in their lifetime.
mouse has since been bred, and researchers are fascinated
by what they’re finding. In its entire genome it has
a single mutation, in a DNA building block known as a nucleotide,
that interferes with the ability of the hormone leptin to
function after docking on the surface of cells where it would
Leptin has been in the news a lot because of its apparent
weight-regulating mechanisms and its ties to type 2 diabetes.
Atkinson says mice studies indicate it’s likely involved
in the development of type 1 diabetes as well.
“If you interrupt the immune system’s ability
to process leptin, the mice no longer develop autoimmunity
and type 1 diabetes,” Atkinson says. “If we can
find an agent that would have the same effect, like a drug
that would block leptin binding to its receptor on certain
immune system cells, we could use a similar type agent to
prevent type 1 diabetes in humans.
“Even though people have looked at it as a molecule
associated with appetite and weight gain, leptin also has
strong effects on the immune system and its production is
related to the level of fat within an individual,” he
adds. “It could be that an individual’s weight
or the amount of fat they carry may modulate in some ways
their immune response, and in the case of a person with type
1 diabetes, this may modulate their progression to diabetes.
With increasing rates of obesity in children, this could explain,
in part, why type 1 diabetes cases are occurring earlier and
earlier in terms of age at disease onset.”
While many researchers devote their entire careers to solving
one extremely specific piece of a puzzle, Atkinson is chasing
“I’ve known Mark for 20 years or so and he really
is one of the most outstanding scientists I have ever met,”
says diabetes researcher Dale Greiner, a professor in the
Department of Medicine at the University of Massachusetts
Medical School. “He’s one of very few individuals
out there who are able to take findings in basic research
and put them into clinically applicable protocols and approaches.
“Most technology that is created in the basic science
realm has multiple applications,” Greiner adds. “It
really is just an individual having the foresight and the
insight to be able to recognize what that can be translated
into, and Mark is just exemplary in that.”
When Atkinson began his career 17 years ago, the study of
diabetes immunology was still in its infancy. Fresh out of
a graduate program in pathology at UF’s College of Medicine,
Atkinson was among the first to show that administering insulin
to mice genetically destined to develop diabetes could thwart
the errant immune system’s battle to destroy insulin-producing
cells in the pancreas. His published findings helped pave
the way for the massive National Institutes of Health Diabetes
Prevention Trial, which tested the approach in humans.
He also was one of the earliest investigators of glutamic
acid decarboxylase, or GAD, an enzyme generated by the insulin-producing
islet cells of the pancreas. Patients with type 1 diabetes
often develop autoantibodies to GAD as the immune system turns
against the body’s islet cells. Atkinson then helped
develop a standardized way to use the presence of these GAD
autoantibodies to predict diabetes.
GAD has since been licensed to a company that is developing
an experimental drug designed to inhibit progression of type
1 diabetes in people. It’s currently undergoing testing,
but studies to date show the drug appears to improve insulin
Atkinson and his UF colleagues, most notably Desmond Schatz
and Michael Clare-Salzler, have spent most of the past two
decades building an internationally regarded research program
on the immunology of type 1 diabetes. They have extensively
studied how to prevent and predict type 1 diabetes. They scrutinized
the genetics of the disease. They launched newborn screening
programs so treatment could be initiated earlier.
Then, about four years ago, they shifted focus, greatly expanding
their research emphasis, buoyed in part by a $10.4 million
grant from the Juvenile Diabetes Research Foundation International
to establish the JDRF Gene Therapy Center for the Prevention
of Diabetes and Its Complications at the University of Florida
and the University of Miami.
UF scientists affiliated with the center, which Atkinson directs,
have been studying gene therapy’s potential to deliver
medicine in novel ways. They also are seeking to engineer
rejection-proof tissues for islet and kidney transplant and
expand existing efforts aimed at tackling diabetes-associated
complications such as vision loss.
Today, as the Sebastian Family Eminent Scholar in UF’s
Department of Pathology, Immunology and Laboratory Medicine,
Atkinson leads a team of researchers involved in many research
• determining the role of environment in the increasing
rates of type 1 diabetes in children.
• pinpointing which blood markers identify children
at risk for type 2 diabetes.
• developing gene therapies for improving whole-body
imaging of islet cells and kidneys.
• developing gene therapies to regenerate islet cells
in the pancreas in those with type 1 diabetes.
• identifying the role of genetics in the formation
and development of type 1 diabetes.
• exploring the use of pharmacologic agents that, on
single application, would offer lifetime acceptance of transplanted
Atkinson says UF scientists have made major advances in tests
capable of predicting type 1 diabetes years before the onset
of symptoms, with approaches that have commercial applicability,
but they and the research community as a whole have been stymied
in their efforts to prevent or reverse the disease.
“With increasing rates of complications, increasing
rates of obesity and increasing rates of type 2 diabetes,
we’re having to expand our efforts, because the scourge
of diabetes is hitting us on all fronts,” Atkinson says.
Indeed, the Centers for Disease Control and Prevention recently
reported that one in every three children born in 2000 will
eventually develop diabetes in their lifetime. For minorities,
the risk can be as high as one in two.
“We absolutely need to
respond to this ever-growing threat of obesity in children
to try to find a way to avert it and prevent it,” Atkinson
says. “In a way, we’re setting ourselves up for
a perfect storm in terms of the combination of increased frequency,
no easy means of prevention and the lack of public understanding
and awareness of how bad diabetes is.”
So Atkinson continues doing what he does best — traveling
the world and preaching the gospel of diabetes prevention,
treatment and cure.
Although he has logged well over half a million miles in the
air and some weeks spends more time on an airplane than in
his laboratory, Atkinson says his schedule offers him an opportunity
to reflect in solitude on that big picture.
“I do see the value of getting that 35,000-foot perspective
on things,” he says.
Sebastian Family Eminent Scholar, Department of Pathology,
Immunology and Laboratory Medicine