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Thomas Jessell, BPHARM, MPS, PhD

Profile written by Robert S Rust, MD, MA

Thomas Jessell, BPHARM, MPS, PhD

Born in London, Professor Jessell received a 1st Class Honours degree in pharmacology from Chelsea College, University of London, in 1973 and in 1974 an MPS from London Hospital. His PhD (Neuropharmacology) was granted by Cambridge University in 1977. His dissertation concerning the release and metabolism of hypothalamic substance P was promptly published in Nature. Four years as Research Fellow at Trinity College, Cambridge followed, including postdoctoral training in the Otsuko Laboratory in Japan, the Fischbach Laboratory at Harvard (Harkness Fellow), and a Locke Research Fellowship of the Royal Society at St. George’s Hospital, London. Ensuing academic appointments with rapid rise in rank were held at Harvard then Columbia, where he was named Professor of Biochemistry and Molecular Physics in 1989. He has also been a Howard Hughes Medical Institute Investigator (1985-), Fellow of the Salk Institute (2000-), Co-Director of the Kavli Institute for Brain Science at Columbia (2003-), and Clair Tow Professor of Motor Neuron Biology (2006-). He holds Honoris Causa Degrees from Umea University, Sweden (1998) and University College London (2004).

Thirty prestigious awards and honors include designation as Fellow, American Academy of Arts and Science (1992), Javits Neuroscience Investigator (1994), Fellow, the Royal Society UK (1996), Taylor International Prize for Medicine (1996), Honorary Fellow, AAN (2000), Jansen Prize in Advanced Biotechnology and Medicine (2000), March of Dimes Prize in Developmental Biology (2001), Member Institute of Medicine (2001), Pasarow Award in Neuropsychiatry (2003), Fellow Academy of Medical Sciences UK (2006), Fellow American Association for the Advancement of Science (2006), Kavli Prize in Neuroscience (2008—with Sten Grillner and former Sachs Award designee Pasko Rakic), Foreign Member, Norwegian Academy of Science and Letters (2009), Society for Neuroscience Education in Neuroscience Award (2009), and W. Maxwell Cowan Award, Cajal Club (2009). He has delivered more than 23 named honorary lectures. His service on editorial boards, editorships, committees and advisory boards has been similarly distinguished. Since 1983 he has been a mainstay of graduate developmental neurobiology courses at Harvard, Columbia, and Cold Spring Harbor. He has directed the research activities of 13 graduate students, 48 postdoctoral fellows, and 3 sabbatical visitors.

Dr. Jessell’s laboratory has played a leading role in characterization of the molecular neurodevelopmental mechanisms whereby naïve neural tube cells assemble from sensory and motor system antecedents into functional spinal locomotor circuits upon the basis of environmental signals that engender fine distinctions of neuronal identity. It is fascinating to understand that the basic mechanisms are found in both invertebrates and vertebrates and that the fundamental aspects of the developmental process involves as well limb, vascular, and organ formation. Differentiation of neuronal function is the result of environmental stimulation, sequence and degree of of kinin activation as reflected in the concentration-dependent effects of sonic hedgehog on establishment of neuronal identity. Not only does the system have remarkable elegance, it implies the developmental connectedness of nature, animate or inanimate. The manner in which dorsal sensory and anterior motor cell fates are intertwined was demonstrated in the Jessell laboratory development in 1992 during the first great burst of sonic hedgehog studies (Ericson et al, Science, cited 442 times). More than forty ensuing Jessell laboratory papers characterize the induction, segregation, selection, chemotropic guidance, polarity and organization of the cells constituting spinal sensorimotor circuits—the total number of citations of these reports to date exceeds 8000. Among the many remarkable observations are description of the essential roles played by such mediators and transcription factors as retinoic acid, on the sensory side by Runk and ETS proteins, on the motor side of FoxP1/Hox protein expression (Liu et al., Neuron, 2001; Dasen et al, Nature 2003, Dasen et al., Cell 2005).

This work has contributed richly to the fundamental understanding of roles that location and connection of neurons in relation to environmental stimulation as well as sequential elaboration of cell-cell communication play in the differentiation of neuronal classes that in turn generate the wide variety of sensorimotor reflexes and functions that characterize the maturing organism. The approach has provided insight into the manner in which the system is able to express innate motor patterns such as stepping (Lanuza et al, Neuron 2004). This conceptual understanding has extended itself to the understanding of the development and function of the entire nervous system, which can be seen as the evolutionary working out of complexity with retention of even very primitive elements but with the capacity for remarkable adaptation. Jessell laboratory work has provided guidance to efforts to promote repair of abnormally formed or injured neural circuitry with the employment of stem cells. Success in such an undertaking depends, of course, on understanding the capacity of neural circuits to recapitulate the normal molecular program of neural differentiation with subsequent establishment of meaningful connectivity. This potential was demonstrated nearly a decade ago by postdoctoral fellow Hynek Wichterle and others in the Jessell laboratory (Cell, 2002, cited more than 500 times). In terms of what may go wrong during development, the laboratory has identified the manner in which such mutant astrocytes found in ALS prompt motor neuron apoptosis (Nagai et al., Nature Neuroscience, 2007). This recognition provides the opportunity to develop novel cellular or pharmacological interventions pertinent to the motor neuron diseases of patients of all ages.

Despite his extraordinary achievements, Dr. Jessell in his quiet and understated manner describes his satisfaction and enjoyment he gains from working out biological puzzles. He describes his own work as “having deciphered a small fragment of a much larger and still elusive puzzle. And when frustration comes it is usually from a sense of impatience the desire to know answers more rapidly than they emerge.” For the young scientist the multifold areas into which Dr. Jessell’s investigations have extended represent abundant opportunities to participate in the elucidation of other aspects of the puzzle. It has become evident that there may be hundreds of types of classes of highly specialized vertebrate neurons, each developing a genetically and environmentally subspecialized function within a local neural network suited by position and connectivity to serve particular roles in the neural regulation and modulation of functions of the nervous and non-neural organ systems. The depth and breadth of the work that Dr. Jessell’s career has undertaken to this point is staggering in scope. But of particular importance is to note that despite the complexity of the system the principles that have been elucidated demonstrate a remarkably highly conserved tendency to employ mechanisms that when understood have elegance and energy-conserving simplicity.

It is possible to view Dr. Jessell’s work as an example of the working out of understanding of neural function by taking up where Sir Charles Sherrington left off. In his Gifford Lectures Sherrington considered the complex question of mind and body. He did so by simplifying the question to the observation that it is possible to conceive of the complexity of both mind and body as the result of successive stages of adaptation of both mind and body to the task of successfully interacting with environmental energy. Sherrington had initially approached the question from the vantage point, as has Professor Jessell, of the spinal sensorimotor reflex arc a reflex that an environmental stimulus and no act of will could generate. He suggested that attention, thought, and behavior were not the integrated function of a few cells but rather “a millionfold democracy whose each unit is a cell.” At the basis of this were the sensorimotor systems that had evolved as the manner in which the organism (with individual variation but similar patterns) encountered and interacted with the environment in which it found itself.

Dr. Jessell’s work is enormously promising with regard to understanding and patching up some of the individual elements of the system, including those that involve the lower motor neuron system. But it also provides, through consideration of other aspects of sensory transduction, the opportunity to consider higher cortical systems. He is providing evidence of a principle that another great scientist—Oliver Lowry—repeatedly emphasized. “You do not find the answer to a biological question on the basis of results that have high p-values. You do so by arriving at an unanticipated result that takes your breath away because of its simplicity and beauty.” This aspect of the achievement of neuroscience during an epoch that corresponds to the work of Dr. Jessell and so many other scientists will likely account for more than the simplification of complex questions to elegant answers memorable in their beauty and simplicity as well as their generation of solutions relevant to human health. The first is the attraction of young bright minds to this work.

Dr. Jessell has been, for twenty years, co-author of what became Kandel, Schwartz, and Jessell’s Principles of Neuroscience, and by the same trio, Essentials of Neural Science and Behavior.” These texts constitute the modern vademecum initially guiding future scientists and clinicians into neuroscience and its clinical relevance. For those who have already been attracted, he is co-author of of Wolpert et al., Principles of Development. The second element of the importance of Dr. Jessell’s work, linking transduction of environmental stimuli to the evolution and development of the state and function of biological organisms is one that was not lost on Sherrington and one must suppose not lost on Professor Jessell: the essential interdependency of all aspects of nature. And as Sherrington cautioned, one that we cannot understand much beyond starting with something seemingly simple and pursuing the understanding of what in time may become a beautiful little element of what remains a complex puzzle for which elegant solutions will be found.