(Circulation. 1998;98:491.)
© 1998 American Heart Association, Inc.
Philip W. Majerus, MD: Bristol-Myers Squibb Award
Ruth SoRelle, Circulation Newswriter
Philip W. Majerus, MD, who first proposed that low-dose
aspirin could be used to treat people at risk of heart attack, stroke,
and other ailments associated with blood clots, has been awarded the
Eighth Annual Bristol-Myers Squibb Award for Distinguished Achievement
in Cardiovascular Metabolic Research. His
proposal that low-dose aspirin could protect those at risk of clot
formation is credited with saving thousands of lives a year.
But that is not his only achievement. Dr Majerus' research into the
role played by platelets in blood clotting and thrombosis is
considered groundbreaking.
Dr Majerus, a professor of medicine and biochemistry and molecular
biophysics at the Washington University School of Medicine in St Louis,
Mo, received the acclaim of his colleagues at the time of the award.
"Phil Majerus, more than any other individual, has produced the most
original body of work on biochemistry of platelets as it relates to
thrombosis," said Joseph L. Goldstein, MD, professor of genetics at
the University of Texas Southwestern Medical Center in Dallas. Dr
Goldstein is a Nobel laureate.
"Philip Majerus made some of the earliest breakthroughs in preventive
cardiovascular treatment and set the stage for many
more," said Hubert Pouleur, MD, vice president of
cardiovascular research and development at
Bristol-Myers Squibb. Dr Majerus received a $50 000 award and a silver
medallion at a dinner in New York on May 13, 1998.
Dr Majerus' work delineated the role of platelets in the clotting
process. Until the results of his research became known, scientists
thought that platelets merely formed the substance of blood clots.
Dr Majerus proved that they precipitate the clotting process. He
discovered receptors on the surfaces of platelets that are the site
of action for the clot-promoting factors in blood. When the factors
bind to the receptors, they accelerate 300 000-fold the activation of
another clot-promoting substance, prothrombin. The activation of
prothrombin results in rapid and specific blood clotting in the local
area.
He is also credited with demonstrating the mechanism behind the
clot-inhibiting effect of aspirin. He showed that low doses of aspirin
modify cyclooxygenase, an enzyme that leads to the
formation of thromboxane. Thromboxane is a
platelet-made molecule that causes the constriction of blood
vessels and aggregation of platelets.
More than that, Dr Majerus showed that aspirin changes platelets
for their entire 2-week lifespan. His work with aspirin was persuasive
in encouraging the use of medication in low doses to reduce all kinds
of destructive blood-clotting events.
His work on clotting led to the description of a lipid called
phosphatidylinositol, which consists of inositol with various numbers
of phosphate molecules added or subtracted. The phosphates change in
response to the extracellular signals. The changes in phosphate act as
signals that are part of a variety of behaviors, from the aggregation
of platelets in the blood to our ability to move our fingers
together. Dr Majerus has cloned many of the genes involved in this
inositol system. Other researchers are now trying to link these genes
to various diseases. "Ultimately, I believe a very large number of
human genes—as many as 500 to 1000—will turn out to be involved in
the inositol system," he said.
Some of the changes in phosphates result in Lowe's syndrome, which
causes mental retardation and eye and kidney disorders. Another gene
from this system is inhibited by lithium, which could lead to a less
toxic form of the chemical that could be used in the treatment of
mental disorders.
Dr Majerus received his bachelor's degree from Notre Dame University
in 1958 and his medical degree from the Washington University School of
Medicine in 1961. He performed his internship and residency at
Massachusetts General Hospital and then was a research associate at
what was then the National Heart Institute. He joined the Washington
University Medical School faculty in 1966 and quickly achieved full
professorships in medicine and biochemistry.
He has previously received the Dameshek Prize for Research from the
American Society of Hematology, the Distinguished Career Award for
Contributions to Hemostasis from the International Society for
Thrombosis and Hemostasis, and the Robert J. and Claire Pasarow
Foundation Award for Cardiovascular Research. He serves
on the editorial advisory board of the journal Biochemistry
as well as the editorial boards of the Proceedings of the
National Academy of Sciences of the United States of America and
the Journal of Biological Chemistry.
