The MDRC J Denis McGarry Lecture: A tribute to an outstanding scientist
J Denis McGarry (1940-2002)
"He had an uncanny knack of making discoveries that changed the way
other scientists thought about metabolism."
Daniel W. Foster
John Denis McGarry, PhD
Denis McGarry was born in Widness, England, in 1940. He did his
undergraduate and graduate work at the University of Manchester, receiving the PhD
in 1966. He did two years of postdoctoral fellowship at the University of Liverpool
and the University College of Wales before joining Dan Foster's lab at Southwestern
Medical Center in Dallas as a postdoctoral fellow in 1968. He was appointed Assistant
Professor of Internal Medicine in 1969 and reached full professorship in Internal
Medicine and Biochemistry in 1997, at which time he was also named the Clifton and
Betsy Robinson Chair in Biomedical Research.
Denis was a gifted teacher who was regularly judged outstanding
by medical students that attended his lectures on metabolism in the Biochemistry
course. He also taught in the graduate school and lectured Internal Medicine residents
and Endocrine fellows.
Research, however, was his passion. He had an uncanny knack to
make discoveries that changed the way that other scientists thought about metabolism.
He defined the malonyl-CoA regulatory system operating through carnitine
palmitoyltransferase 1 (CPT1) and showed that the ketosis of starvation and the
ketoacidosis of insulin-dependent diabetes was the consequence of a glucagon-induced
fall in malonyl-CoA. Solution to the problem of ketogenesis had eluded such illustrious
names as Krebs, Wieland, and Lehninger. He subsequently showed that the malonyl-CoA/CPT1
system operated in many other tissues. Under his leadership the laboratory cloned and
sequenced the involved genes and unequivocally proved that CPT1 of liver was distinct
from CPT1 of muscle and that CPT1 and CPT2 were separate enzymes derived from different
He also devoted considerable energy to the mechanism by which
glycogen was synthesized from glucose after a fast. In contrast to conventional
wisdom, he showed that the indirect pathway, the Cori cycle (glucose > lactate >
glucose-6-phosphate > glycogen) was dominant over the direct pathway (glucose >
glucose-6-phosphate > glycogen).
In 1992, he published a famous review paper in Science
(Science 1992 258:766-770) entitled "What if Minkowski Had Been Ageusic? An
alternative angle of diabetes". He suggested that scientific focus on abnormal
glucose metabolism had masked the critical importance of abnormal fat metabolism,
especially in type 2 diabetes mellitus. Subsequent to this paper there was a huge
swing by investigators toward the key role of abnormal lipid metabolism in insulin
resistance and lipotoxic damage to tissues as diverse as the heart and the beta-cell
of the pancreas.
In late April 2001, Denis was diagnosed with glioblastoma
multiforme after the sudden appearance of expressive aphasia. He received the 2001
Banting Medal for scientific achievement from the American Diabetes Association, but
his health sadly prevented him from giving the lecture. It was given beautifully by
ADA President Bob Sherwin who emphasized studies on the role of dysregulated fatty
acid metabolism in the diabetic state. Denis felt blessed that he was able to be
present and receive the medal.
In addition to the Banting Medal, Denis had previously received
the Lilly Award, the Herman O. Mosenthal Award, the Joslin Medal, the David Rumbough
Scientific Award and the Grodsky Award.
As his death approached, his friends wanted to raise money for a
distinguished chair before he died. The size of some of the gifts from the faculty
was astounding - $100,000. Pledges for a million dollar were quickly raised. The
University of Texas Medical School normally gives an actual chair to the major
donors, but the donors wanted Denis to have it. There was a reception in his home to
award it and those present will never – ever – forget a classic scene. Denis was
sitting in the chair and kneeling on the floor before him were Steve McKnight, Mike
Brown, Joe Goldstein and another scientist who held his hand. It was incredibly
touching. Denis McGarry died peacefully at his home in the presence of his family
on the evening of January 27, 2002.
A remarkable thing about Denis was the vast number of deep
friendships he had in the world of diabetes and the scientific community. He was
extremely rigorous, pertinent and original in the way he approached a scientific
problem, often starting from simple physiological observations leading to testable
hypotheses. He acted like a magnet for young investigators who always wished to
discuss informally with him and who much appreciated his original turn of mind with
a vision of biology and physiology at large. His papers were extremely well written
with a touch of literacy and perhaps the writer James Joyce that he admired so much,
also native from Ireland, inspired him. Denis was a joyful person and he could test
and tease you in a bar anywhere in the world by asking with a playful smile "
What was the most important discovery and experiment in the field of diabetes?"
Like every one but with some doubts because of the triviality of the question you
would answer that it is the discovery of insulin. He would smile again and say "
Absolutely not! It is the removal of a dog pancreas by Oskar and the serendipitous
observation of the flies attracted by the sweet urine... and not repelled by the
fat-derived acetone." Without saying he would win this lost battle for you with
a little cigarette remain in his mouth, the smoke volutes going to heaven and an
excellent glass of red Bordeaux in his hand... and as a compensation of you feeling
so dumb, magnanimous he would offer you another glass. Denis was also humble and he
would say "Well besides Mozart, Einstein and few others among centuries who will
remember what we did in a hundred years?"
No comments about Denis McGarry would be complete without
mentioning that he was a devout Roman Catholic.
At the beginning of the 7th century, Isadore, Archbishop of
Seville, gave his prescription for a good life.
Learn as if you were to live forever.
Live as if you would die tomorrow.
Denis did both. He learned all his life in science. When death
came he was ready.
Text written by Dan Foster and Marc Prentki
The J Denis McGarry Lecture
In the memory of John Denis McGarry, the Montreal Diabetes Research
Center is proud to organize each year "The J Denis McGarry Lecture" given by world-leaders
and outstanding speakers.
Previous J Denis McGarry lecturers were:
Institution and title of the lecture
||Scott M. Sternson
||Janelia Research Campus, Howard Hughes Medical Institute, MD
The systems and molecular neuroscience of hunger
||C. Ronald Kahn
||Joslin Diabetes Center, Harvard, MA
Interactions between genes, environment and the gut microbiome in insulin resistance and metabolic syndrome
||University of Texas Southwestern Medical Center, TX
Diabetes, obesity and the central role of the adipocyte in maintaining systemic homeostasis
||University of Cincinnati, OH
Metabolic peptides, food intake and body weight: problems with the model
||Steven E. Kahn
||University of Washington, WA
The beta-cell in type 2 diabetes: is she still the main culprit?
||University of Texas Southwestern, TX
Unique dependence of mouse embryonic stem cells on threonine catabolism
||Karolinska Institute, Sweden
Gene/Environmental influence on skeletal muscle insulin sensitivity
||Harvard Medical School, MA
Regulation of Brown Adipogenesis: Mechanisms and Therapeutics
||Columbia University, NY
Understanding beta-cell failure: lessons from Foxo biology
||Gökhan S. Hotamisligil
||Harvard School of Public Health, MA
Inflammatory basis of metabolic diseases
||Rudolph L. Leibel
||Columbia University, NY
Quantifying pancreatic beta-cell mass in vivo in rodents and humans
||Gerald I. Shulman
||Yale University, CT
Role of dysregulated intracellular lipid metabolism in insulin resistance