The Genesis of Knowledge: Caretakers of Contemporary Medical Renaissance

As we get older, we cling to the things that define our identity, including belief systems. One does not transcend this truism of human nature by becoming a practitioner of science and medicine. In fact, traditional teachings and dogma in these revered disciplines are often adopted as "self" and adhered to with heightened emotion, sometimes to the point that new data contrary to the held belief is seen as a personal threat or insult. An exception to this phenomenon is the young scientist... the novice with fresh, non-biased (albeit naive) conceptualizations of complex systems of nature. Not only may they encounter harsh criticism for their creative thought, there are limited resources to support the methodical testing of their hypotheses. Consequently, without adequate preliminary data, they are disadvantaged in the pursuit of competitive granting mechanisms. Fortunately, for many of these beginning investigators, hope is not lost, as there exists an entity, perhaps best described as an "angel investor" and certainly acting as a guardian angel, that is committed to providing ground-breaking support for novel approaches and technologies in medical neuroscience.

The Jerome Lyle Rappaport Charitable Foundation generously endorsed me as a fellow soon after I graduated from my residency program in psychiatry for a series of experiments exploring a novel approach to the study of emotional pathophysiology. The Rappaport Foundation championed, and invested in, work that most granting committees would consider, at best, "high risk". The proposal involved redirecting our knowledge and experience in neural transplantation for neurologic disease toward the investigating the functional neuroanatomy and physiology of fear and anxiety—perhaps the most debilitating components of virtually every major psychiatric disease.

Although considered modest in relation to many other awards received by seasoned scientists, the $25,000 grant was more than sufficient to finance pilot investigations to establish proof of principle. And for a cash-poor neophyte medical-scientist proposing untraditional methods, for all intents and purposes, this was a financial windfall. As the experiments were designed and executed, interest (and, indeed, fascination) in the work began to grow among my colleagues and students. I mentored and supervised five pre-med undergraduates who participated in projects under Rappaport funding. Three of these students graduated with highest honors for their research, two of whom then matriculated at esteemed medical schools, and the other landed an important research directorship position at Harvard Medical School. The fourth student has been accepted into Georgetown University’s pre-med program, and the fifth student was able to transfer from a lesser-known undergraduate college into Brown University to study medical neuroscience. It is clear that their training and experience during this dynamic period of discovery played a major role in not only their choice of career path, but in empowering their applications for advanced training at esteemed institutions. The impact of the gift from the Rappaport Foundation has been far-reaching and long-lasting, as the course of my research has been so decisively and positively influenced and the lives of my advisees have been permanently charmed.

The Rappaport award allowed us to demonstrate that inhibitory, GABAergic neurons can be engrafted with precision into the region of the brain that controls anxiety and fear, and these grafts modulate, or “quiet”, this emotional circuitry in situations of stress. Proposed as a novel approach to delineate the cellular and molecular substrates of mental illness, and to investigate the physiology of emotional circuitry responsible for disorders of mood and perception, this application was accepted by the NIH granting committee without revision, and was viewed as an innovative advancement and a powerful investigational tool in the neuroscience of emotion. A five-year NIH K08 award was granted for the development of neural transplantation for investigations of the pathoetiology and therapeutic interventions for neuropsychiatric diseases. This award provides ample funding over an extended period of time, thus allowing the construction of a laboratory under my direction devoted to a new area of psychiatric neuroscience. I take pleasure in the possibility that in the coming years, the members of the Rappaport Foundation will observe the continued growth of this approach and this body of knowledge, perhaps remembering its modest beginnings when they provided critical inertia to an experiment that proposed a method for repair of the mind.