What makes someone a genius? According to Nobel Laureate Eric R. Kandel, M.D., it is a person who is a “game-changer” and who “through their work, permanently changed the way we perceive the world.” It is less about IQ and more about “drive, persistence, and creativity.” At the 92nd Street Y’s third annual 7 Days of Genius in Manhattan, four eminent scientists, arguably geniuses themselves, discussed historical geniuses of the mind, brain, and molecules. The three speakers included two members of the Dana Alliance, Larry W. Swanson, Ph.D., and Thomas M. Jessell, Ph.D., as well as Robert Michels, M.D. Kandel, also a Dana Alliance member, moderated the event.
The idea that someone who has become paralyzed from the waist down could regain the ability to walk fascinated me from the moment I learned it was possible.
Hybrid brain-machine interface (HBMI), also known as recurrent brain-computer interface, could make this a reality. Say you have a serious spinal cord injury. Reclaiming use of your legs is theoretically possible because the neurons that control motor function are still intact, as are the muscles themselves (although they atrophy over time).
Ultimately, HBMI researchers would like to create an implantable chip that could assume the role of the spinal cord and relay sensory and motor information between the brain and the affected limbs. Excited to learn more, I attended a lecture presented by Dana Alliance member Thomas Jessell of Columbia and hosted by the University’s Mind Brain Behavior Initiative, sponsored by The Dana Foundation.
Dr. Jessell, a tall man described as a “better-looking Colin Firth,” has a delightful English accent and an even more delightful mind. His research, which focuses on how neural circuits that control motor function are built and organized, has greatly aided the cartography of the nervous system. He spent a great deal of the lecture discussing stem cell research and its role in motor system therapy, to which his work has significantly contributed.
During the lecture, I realized that the motor system is perhaps the body system most taken for granted. Of the 10,000 cell types in the central nervous system, motor neurons are the only ones that communicate with the outside world—via our actions, they enable us to turn our thoughts and feelings into behavior.
One evolutionary theory holds that motion was the reason brains evolved in the first place. The motor system is remarkably complex; there are 50-70 different subtypes of motor neurons, which correspond to the muscles they innervate. In invertebrates, motor neurons can act on muscles in either an inhibitory (relaxing) or excitatory (contracting) way. In vertebrates, motor neurons can only excite muscle fibers (cause them to contract), which is why we often understand muscles as working in pairs to control limbs (think bicep and tricep, or quad and hamstring.) Thousands and thousands of cells must work flawlessly in concert to allow us to do things as common as making a sandwich or walking down stairs.
When things go wrong in the motor system, it makes life very difficult. Because of increased visibility, most people are aware of diseases like Parkinson’s and Huntington’s disease and how tragic they can be. Dr. Jessell described the evolution of therapies for amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s Disease.
Scientists have found a way to derive stem cells from adult somatic cells, like skin cells. These stem cells are induced pluripotent stem cells (iPSCs). Pluripotent stem cells can develop into any types of cell in the body, depending on cellular signals in their environment. By introducing certain signals to the iPSCs, researchers can encourage them to differentiate into cells like motor neurons (in the case of studying ALS). These motor neurons behave exactly as naturally-derived in vivo neurons. Furthermore, they are patient-specific, because they are derived from the patient’s own cells.
Creating patient-specific iPSCs opens the doors for all types of clinical research. Therapies can be safely tested on human tissue or customized to particular individuals. Some researchers are trying to determine how to reprogram damaged cells into healthy ones for re-introduction into the human body. The field of iPSC research may hold the cure for a host of neurological diseases that plague us today.
For more reading about ALS, check out the piece “Night,” by the late historian Tony Judt. It’s an incredibly honest reflection of his battle with ALS and his emotional experiences with the disease. A copy of the article was provided for us at the lecture, and I made the mistake of reading it in public. Let me just say that I strongly recommend reading it with a box of tissues nearby (this is not the first time I’ve made this recommendation; I must read a lot of depressing stuff).