Among Health, Policy, and Security
Dr. Lance L. Simpson
About Dr. Lance L. Simpson
Dr. Simpson obtained his undergraduate training (1962 to 1966)
at Vanderbilt University in Nashville, Tennessee. He had a dual
major in physiological psychology and molecular biology. He obtained
his Ph.D. training at the University of California in Berkeley (1966
to 1969). He worked in the laboratory of Professor Melvin Calvin,
Nobel Laureate in Medicine and Physiology. During his Ph.D. training,
Dr. Simpson did research on drugs and toxins that affect the nervous
Upon completing his Ph.D. studies at the University of California,
Dr. Simpson was accepted into a special training program at the
College of Physicians & Surgeons at Columbia University. This
program, which was funded by the National Institutes of Health,
placed basic scientists into clinical departments. The goal of the
program was to introduce young investigators to clinical issues
and settings, in the hope that they would do research with a high
likelihood of clinical impact. The program sought to discourage
trainees from entering clinical practice, but there was strong encouragement
for trainees to remain associated with clinical departments. Dr.
Simpson has followed the model envisioned by the program, in which
a basic scientist works on problems of authentic clinical importance.
During his Post-Doctoral training (1969 to 1971), Dr. Simpson worked
under the joint sponsorship of two senior investigators: Dr. Maurice
Rapport, a neurochemist, and Dr. S.C. Wang, a neuropharmacologist.
The Fellowship allowed Dr. Simpson to continue his work on various
drugs and toxins that affect the nervous system.
After completing the Fellowship, Dr. Simpson was asked to join the
Faculty at the College of Physicians & Surgeons. He remained
there until 1984, when he left to join the faculty at Jefferson
Medical College in Philadelphia. He is currently Professor of Medicine,
Professor of Biochemistry and Molecular Pharmacology, and Director
of the Center for Research on Bioterrorism and Biodefense.
Throughout his career, Dr. Simpson has maintained a strong interest
in various agents that act on the nervous system. However, his major
focus has always been on botulinum toxin, an agent that acts selectively
on cholinergic transmission. In the early stages of his career,
this interest manifested itself in two ways: 1.) elucidating the
mechanism of toxin action, in the hope of identifying pharmacological
approaches to preventing or reversing toxin-induced paralysis, and
2.) utilizing the toxin as a pharmacological tool to dissect subcellular
and molecular events in exocytosis.
The interest in developing ways to counter the effects of botulinum
toxin has continued, but with a broader perspective. In addition
to seeking ways to counter botulism as a naturally-occurring disease,
Dr. Simpson has also become involved in work to counter the toxin
as a potential agent of bioterrorism and biological warfare. The
major thrust of this work has been in the area of vaccine development.
On the other hand, research utilizing the toxin as a pharmacologic
tool has been largely replaced by a new endeavor. Dr. Simpson and
his colleagues have used the techniques of molecular biology to
alter the toxin molecule such that it retains the ability to enter
the body (i.e., binding and transcytosis across gut and airway epithelial
cells), but it has lost the ability to poison cholinergic transmission.
This modified polypeptide has been shown to be useful as a carrier
molecule in the creation of oral and inhalation drugs and vaccines.
This work has resulted in one patent, and three patents are pending.
A large number of junior investigators (PhD, MD and DVM) have completed
fellowships or related types of training programs with Dr. Simpson.
In addition, several senior investigators have come to the laboratory
for their sabbatical leaves. These scientists have made enormous
contributions to the success of the research program.