When
did you first know you wanted to be a scientist, and did any
particular experience, event, or person influence your decision?
It was basically assumed that I would become a "doctor"
in my family, and I remember my mother reading to me from the N.Y.
Museum of Natural History science encyclopedia as I rowed her on a
lake in the Catskills. My father worked for a time in the cafeteria
of the museum. I was very fortunate to have a full Pulitzer
scholarship to Columbia University, a
university I never would have thought to apply to but for an
excellent English teacher.
The M.D./Ph.D. program at Duke was fantastic and I had a generous
mentor, Dr. Harold Lebovitz. An important part of the program was
help in affording medical school, and I could have gone into
clinical medicine or research, depending on how research progressed.
It always seemed to progress well. Dr. Lebovitz helped arrange at
the time of my Endocrine fellowship for me to go to the National
Institutes of Health to work in the laboratory of Marshall Nirenberg
at the time the first monoclonal antibodies were being made. A
colleague from Duke, Barton Haynes, was there at the same time,
making rabbit antibodies to T cells in Dr. Fauci's laboratory and we
were able to make some of the first anti-T cell monoclonals
together, as well as monoclonals to islets and neurons.
What,
in your opinion, is the significance of your work for the field?
I have pursued the hypothesis that type 1 diabetes is a chronic
autoimmune disorder and, more important, that it is a predictable
disease. In retrospect that seems obvious, but at the time I began
my research in this area the majority of investigators believed in
the acute development of diabetes (e.g., acute viral infections) for
the majority of patients and there were many reports using our
prior, more-difficult assays of immune phenomenon that poorly
correlated with disease outcome. I have been fortunate at Duke, the
Joslin Diabetes Center, and the Barbara Davis Center to be able to
investigate both human and animal models. Both have provided
concordant data, and with an international effort in this area, as
well as international workshops to improve assays, it is now
possible to predict type 1 diabetes in man and to prevent it in
animal models. A large clinical effort is underway to prevent type 1
diabetes in children and a larger basic research effort will
hopefully provide the knowledge to make this possible, including the
development of immunologic vaccines for the prevention of
autoimmunity.
What
were the greatest challenges in performing and presenting your work?
Initially the work indicating chronic progression to diabetes was
greeted with skepticism by a few, and I remember a small NIH
conference where a senior diabetologist stated after I gave a talk
"that is not my clinical experience." This was perhaps a
minor problem in that investigators in many countries contributed
rapidly to a large body of work. I was fortunate in receiving grants
when I needed them during some difficult periods in terms of NIH
funding. One of my colleagues, when I indicated that somehow the
needed grant always came through, indicated wisely that "I was
still here." I was also fortunate to be at institutions (Joslin
and Barbara Davis Centers) where there is philanthropic support,
something I believe has developed at many institutions and will
provide stable support for the next generation of researchers.
The biggest challenge now is the difficulty of performing
clinical trials to take the basic research to the level where we
actually are able to prevent diabetes with our imperfect
understanding of the disorder and lack of markers in humans of the T
lymphocytes that cause disease.
What
unexpected or serendipitous events arose in the course of your
research?
The first monoclonal antibody I produced (A2B5) reacting with a
complex ganglioside was made after immunizing with chicken retinal
cells, but reacts beautifully with the surface of islet cells and
thus provided me with an important reagent when I turned to studies
of diabetes.
When I first came to the Joslin Diabetes Center, Dr. Stuart
Soeldner had collected for more than a decade metabolic data and
serum on identical twins of patients with type 1 diabetes, with a
small number actually followed to diabetes. This serum bank combined
with the metabolic data saved approximately 15 years of time in
discovering the metabolic chronicity and autoantibody predictability
of progression to diabetes.
What
is your prediction for the state of our knowledge about your field 10
years from now?
I believe the molecular puzzles of autoimmunity will be solved
for many disorders and in particular for type 1 diabetes.
Importantly, assays that accurately measure the antigen specific T
cells that cause disease and protect from it will be defined, and
clinical trials will utilize this knowledge to devise preventive
therapies.
Which
of your professional achievements brings you the most satisfaction?
The realization and early formulation that type 1 diabetes is a
chronic autoimmune disorder that could be predicted. This included
dividing the development of diabetes into a series of stages
beginning with genetic susceptibility, followed by triggering,
autoimmunity, and then progressive metabolic deterioration.
What
lessons would you draw from your work to pass on to the next
generation of researchers?
-
Even for an ancient disorder such as type 1 diabetes, the
fundamentals of disease may be completely misinterpreted—such as
the time course of the disease.
- A dramatic observation made in a small number of subjects (6 BB
rats, 5 monozygotic twins) is likely to be generalizable despite a
field that has a different paradigm.
- An awful lot of time and publications are wasted with reports not
able to distinguish the noise of assays from true biologic
phenomenon, and international "blinded" workshops are very
important in advancing fields especially in the areas of assays.
Would
you like to leave any other comments about your work or share a
personal side of yourself?
The system has been very forgiving, I have been lucky, and I have
had great colleagues, and thus currently I head a center providing
diabetes care and seeking to prevent and cure type 1 diabetes. I
believe such interdisciplinary centers are essential to speed future
medical research. As my fellows will attest, I have always erred on
the side of sharing our research results as early as possible, as I
realize that important medical advances will always be too late for
someone. As I look ahead, I believe it is the job of this generation
of university administrators to create endowments that will support
basic research, but also to support academic clinical programs. In
the past, clinical programs provided extra funds to basic research,
while at present I believe it is easier to fund basic research and
more difficult to fund academic clinical care, which is essential to
advance clinical research. Perhaps I am lucky where I am, but I
believe there is a great opportunity to now create such endowments.
George S. Eisenbarth, M.D., Ph.D.
Barbara Davis Center for Childhood Diabetes
University of Colorado Health Sciences Center
Denver, Colorado, USA
n
this interview, Special Topics talks with Dr. George
Eisenbarth about his highly cited work on diabetes. Dr.
Eisenbarth ranked among the top 20 scientists in terms of
total citations in our analysis of diabetes research over the
past decade, with 110 papers cited a total of 1,825 times. In
the 
Web product, Dr. Eisenbarth’s work can be found in the field
of Clinical Medicine. Dr. Eisenbarth is the Executive Director
of the Barbara Davis Center for Childhood Diabetes and is also
Professor of Pediatrics, Medicine, and Immunology at the
University of Colorado Health Sciences Center in Denver.