Linkages 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 system.

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.