Abstract
We were all very saddened to hear that Dr. Jerry Silver passed away on January 7, 2025. Jerry was a great neuroscientist who brought new insights to the field of spinal cord injury. We have asked several of his colleagues and past students to describe his impact on their work and careers.
With Jerry’s passing, our worldwide spinal cord injury research community loses a pioneer who has influenced and shaped the field for more than a quarter of a century. My first encounter with Jerry—we were both young postdocs—was around 1979 at one of the famous lunchtime seminars at the Harvard Neurobiology Dept. (the kitchen was in the seminar room; everyone, except for the speaker, was eating). Jerry reported on a suggested role of glia-dependent extracellular “tunnels” in peripheral and optic nerves as a possible guidance structure for regeneration. From there, the step to astrocytes and the extracellular matrix was almost obvious. Microscopic tissue localization studies suggested a barrier and growth inhibitory role of chondroitin sulfate proteoglycans (CSPGs) at lesion scars. From there on, Jerry invested all the efforts of his lab to demonstrate the regeneration-restricting role of CSPGs and the glial scar in the injured spinal cord. He digested or suppressed CSPGs in different ways in various animal models of CNS injury. The results of these studies became textbook knowledge. But they also led him to develop an approach with clinical potential; a CSPG receptor-blocking peptide is currently in a Phase 2 clinical trial in spinal cord-injured patients.
My interactions with Jerry on many meetings and occasions over these many years were of a collegial “competitor-collaborator” type, which is so typical for science. We always greatly enjoyed our discussions in Neuroscience Meeting Poster halls, during workshops in Italy or Keystone, or on the beach of Bermuda (during an ISRT SCI meeting; Jerry was elected the “hairiest neuroscientist”). Our approaches—blocking CSPGs or Nogo-A—were very complementary, and we were both looking forward to discussing the outcomes of our clinical trials, which ran almost in parallel. It should not be—but Jerry’s legacy—his concepts, his commitment to spinal cord injury, and his specific clinical approach—will live on and will continue to inspire and encourage us to reach for the goal of a better life for spinal cord injured people.”
Written by Martin E. Schwab, MD, PhD
Jerry was one of the most creative scientists I have met, who constantly thought outside the box. Almost every week he would come into the laboratory all excited about a new experiment or idea he thought of. I particularly remember when he was obsessed about cartilage not being innervated and his determination to figure out why. This obsession led to the discovery of CSPGs being major axon inhibitory molecules in both neural development and regeneration.
Written by George Smith, PhD
Jerry was a wonderfully creative scientist who had the remarkable ability to see what others overlooked. Some of my best memories with him are of us sitting at the microscope together. While Jerry will be remembered by the scientific community largely for his seminal findings, I will remember and miss his mentorship the most. Jerry’s support of his trainees didn’t end with their time in the lab—he was their forever mentor and champion.
Written by Veronica J. Tom, PhD
Jerry Silver was one of a kind. While one could (and should!) write reams about his brilliance, intuition, accomplishments, and eccentricities, I offer merely one anecdote here that has always stayed with me. Having just decided to take the daunting step of going to graduate school, feeling vulnerable and nervous, I had a most fortuitous opportunity—an interview with Jerry. With animated eyes and exuberant enthusiasm, he said, “Snow (he called me ‘Snow’ from day 1), look at this! Why don’t axons grow through here?” pointing to an electron micrograph of the rat spinal cord roof plate. “You should study that!” The rest is history. Jerry’s enthusiasm for science, his grand ideas, and his penchant for ignoring barriers were contagious to all. Although I had no idea what a wild ride I was in for, I was hooked, thanks to one great mentor. Through my years in the Silver Lab, Jerry and all the many interesting and talented people who worked and played there changed my life in hundreds of fabulous ways. Although Jerry is gone, he still holds such an enormous place in our collective hearts that we will probably feel his presence, be encouraged by his abundant passion, and hear his distinctive laugh for eternity. I will always be honored to have been one of Jerry’s kids.
Written by Diane M. Snow, PhD
Jerry Silver’s passion was the influence of molecules in the extracellular matrix on axons. Early in his career he investigated axon guidance by glial structures in the spinal cord and corpus callosum and realized that there were axon growth barriers that contained chondroitin sulfate proteoglycans. Some of these proteoglycans were very inhibitory to axon growth. In embryos, inhibitory proteoglycans could guide growing axons; for instance, in the retina axons are directed toward the optic nerve head by a proteoglycan gradient. The discovery that shaped most of his research was in 1990, when he, with Diane Snow, Vance Lemmon, and others showed that inhibitory CSPGs are strongly associated with lesions in the spinal cord and brain and could therefore be a major factor in blocking the regeneration of axons in the injured adult nervous system. He subsequently showed that these CSPGs could paralyze regenerating axons, causing them to produce dystrophic endbulbs instead of growth cones. Subsequently, Jerry and his colleagues found a neuronal receptor for the CSPGs, PTPσ. A peptide inhibitor was developed, which enabled axon regeneration in the damaged spinal cord, and a development of this peptide is now in clinical trials for spinal cord injury with NervGen, a company that he helped to found.
Written by James Fawcett, PhD
I first came to know of Jerry through his work with a young neurosurgeon, Michael Kliot, who had studied dorsal root entry zone bridging with embryonic astrocytes seeded on a scaffold. Later, like other surgeons, I explored the effects of Adcon-L, one of Jerry’s inventions to reduce post-surgical scarring in discectomies. Subsequently, Jerry was in the pantheon of scientists who initially unraveled the nature and extent of axon-inhibiting molecules in the CNS between 1990 and 2010. Subsequently, I serve as an advisor to the clinical trial program for NVG-291, for which initial results are encouraging. Jerry brought energy and enthusiasm to every encounter, and he passed too soon.
Written by James Guest, MD, PhD
I first met Jerry in the 1980s when my colleague, Carl Lagenaur, and I talked to him and his team at Gliatech about L1cam as an agent for nerve regeneration. Very shortly after that, I moved to CWRU, and Jerry was my colleague in the new center/department founded by Story Landis. I published two articles with him when his students, Diane Snow and Perry Brittis, did experiments in my lab. On a daily basis, I saw his Cajal-like brilliance in plucking novel hypothesizes about development and regeneration from sections of the brain and spinal cord. I also experienced his “class-clown” sense of humor just as frequently. A passionate and outgoing scientist like Jerry pushes everyone in the vicinity to try harder and think more creatively.
Written by Vance Lemmon, PhD
Taking preclinical data into patients with spinal cord injury to improve functional restoration is a huge step forward. It’s been a true pleasure collaborating with you over the past several years as we worked together on the clinical trial based on your groundbreaking research. Transitioning this knowledge into an FDA-randomized placebo-controlled clinical trial is a remarkable achievement. I’ve been consistently impressed by your persistence, dedication, and passion for improving the quality of life of our patients. We will miss you greatly and will carry forward your example as we continue this important work.
Written by Monica A. Perez, PhD
I first met Jerry at a spinal research meeting in Bermuda when I was a young post-doc. I was enthralled by his brilliance and his character. He was presenting a “big story,” with his characteristic exuberant style, dramatically declaring to the conference that he had something new and groundbreaking and insisting that attendees keep absolute confidentiality of what he was about to reveal. Sure enough, it turned out to be a game changer. This was work demonstrating that reactive extracellular matrix at the lesion site is directly associated with failure of axon regrowth in vivo. These seminal findings were published in consecutive articles in Nature and the Journal of Neuroscience and influenced a subsequent wave of research into targeting scar-associated growth inhibitors. Jerry’s work, and Jerry himself, had a huge influence on my own research, as I had recently become one of a group of researchers in the field who were devising strategies to “inhibit the inhibitors,” focusing our efforts on overcoming the factors that block regenerative growth and neuroplasticity. Jerry was always a champion and supporter to me and to many others who were following in his footsteps, and we spent many hours at conferences, at posters, and in the bar, discussing all things relating to glia, matrix, and the scar. Jerry was a true pioneer, and his influence in our field was enormous. But he was much more than that, a larger-than-life character with a huge personality and a big heart, always championing the next generation of researchers and stimulating epic debates. Conferences were always more exciting (and much more fun!) with him around. His loss is felt deeply by our community, and we wait in hopeful anticipation for the results of the NVG-291 trial, a culmination of his pioneering life’s work. His mentorship of many of the next generation of researchers will keep his dream alive that we will one day change the outcome for individuals living with SCI.
Written by Elizabeth Bradbury, PhD
My first meeting with Jerry was at a trainee lunch when I was a postdoc. He had published his famous “Regeneration Beyond the Glial Scar” review article just a couple of years earlier. I didn’t know it at the time, but the insights I gained from that article would have a huge impact on my career. That lunch with Jerry remains one of my most memorable moments as a postdoc because it felt like talking to an oracle about axon regeneration. Several years later, after I started my own lab and published my first article on perivascular fibroblasts, I ran into Jerry at SFN. I didn’t think he would remember me, but he said, “Of course I do—you are Scar Man II.” It is one of the greatest compliments I have ever received, but in a very Jerry-like way.
Written by Jae K. Lee, PhD
I remember reading an early article by Jerry and colleagues that provided compelling evidence for the formation of a molecular barrier at the lesion site that impeded long axon regrowth. This publication with beautiful images of regenerating axons remote from the injury site had a major impact of my views for improving function in people living with SCI. The last time I saw Jerry was when he visited Miami, and I had the opportunity to spend quality time with Jerry, Mary Bunge, and James Guest. We had a lively dinner discussing Schwann cell migration, CSPG digestion, and the need for combination therapies to treat paralysis. We were all very interested in Jerry’s lifelong work on regenerating the injured spinal cord and his regenerative peptide, which is currently being tested in a clinical trial—the results of which will be announced soon. Jerry was a towering figure in the field of SCI and neural repair, and his many contributions to science will be felt for many years to come.
Written by W. Dalton Dietrich, PhD