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The Centrality of the Peripheral Nerves: The Anatomical Record Showcases New Findings on Regeneration of Peripheral Nerves in our Latest Thematic Papers Issue

2018; Wiley; Volume: 301; Issue: 10 Linguagem: Inglês

10.1002/ar.23935

1932-8494

Jeffrey T. Laitman, Kurt H. Albertine,

Neurology and Historical Studies

In the realm of science there are words that at times "miss the mark," sometimes even unintentionally denigrating the item or topic that they represent. Take the term "gross," for example. Both authors of this Editorial proudly teach gross anatomy and have thoroughly enjoyed opening the minds of budding physicians and surgeons by enabling their first mesmerizing encounters with a heart or a brain. Yet when we tell people what we teach, we often engender a sneer of derision. "How gross!" is the sarcastic remark we have often heard, as our students or colleagues see the word in its adjectival meaning of unacceptable, shameless, course, vulgar, unpleasant or (for one of us) fat (as in "I've put on weight and feel gross in my pants.") Uh, no, dear colleagues, the word "gross" in our field denotes that which you see with the naked eye. It is used in contradistinction to "microanatomy," that which one needs a microscope to visualize. Oh, how many times we have had to explain this (along with our interesting odor) to our family and/or nonanatomical colleagues! In the world of the nervous system a similar relentless denigration has occurred with the topic of this Thematic Papers Issue: Peripheral Nerves. While President Bush the Elder anointed 1990–1999 as "The Decade of the Brain," with every millimeter of that magnificent orb given focus, attention, and love (not to mention lots of extra funding!) nary a whisper was made about those peripheral nerves. For many, its literal meaning of nerves serving the peripheral corpus away from the brain has been interpreted as secondary, less consequential, innervation. While there is a Peripheral Nerve Society, with its own eponymous journal, that gives a clarion call for peripheral neuroanatomists, their voices are overwhelmed by the cacophony of Brain publications that claim the headlines. To many, peripheral is just that, and the mindset that comes from the name has pushed much crucial recognition and discovery to the back burner. This current Thematic Papers Issue of The Anatomical Record on "Peripheral Nerve Regeneration and Repair," Guest Edited by internationally renowned neuroanatomist and neurologist Xavier Navarro of the Institut de Neurociencies, Universitat Autonomia de Barcelona, brings peripheral nerve science to the fore by showcasing exciting current research (Navarro et al. 2018, this issue). The issue stemmed from presentations at the 4th International Symposium on Peripheral Nerve Regeneration that occurred 6–8 July 2017 in Barcelona, Spain. José Luis Trejo of the famed Cajal Institute in Madrid, our intrepid Associate Editor specializing in aspects of neuronal circuitry, was integral in working with Professor Navarro in bringing the presentations to our journal and shepherding this wonderful Thematic Issue to fruition (Trejo 2018, this issue.) The Anatomical Record boasts a long and proud history of reporting findings on both the basic descriptive and comparative anatomy of mammalian peripheral nerves sensu lato and also on the specific topic of this issue, peripheral nerve development and regeneration. Indeed, from the very birth of The Anatomical Record, and our first volume in 1907, the topic of nerve growth has been featured. Our first volume included both Abstracts of recent presentations and full-length reportage by none other than Ross Granville Harrison, arguably the greatest scientist of the 20th century who did not receive a Nobel Prize (Nichols 1961; Federoff 1987; Noden 1987; Palay 1987). Harrison's name and contributions are known and sacred to most anatomists, zoologists, embryologists, and neuroanatomists (if you don't know about him, shame on you, and move away from that microscope!) A little background on Harrison and his accomplishments are in order. He took his PhD from his hometown Johns Hopkins in 1894 and his MD from Bonn, Germany in 1899 where he met his future wife (this becomes relevant later) then returned to Hopkins to commence his career. In 1907, he moved to Yale, his home for the remainder of his scientific life, both in the Department of Zoology that he chaired, and in the medical school. The list of research students and faculty he mentored is extraordinary (Noden 1987) and place him as the root of many academic lineages (e.g., one of us, JL, whose graduate degrees are from Yale, is an academic great-grandchild of Harrison). Harrison's genius was multi-dimensional, but arguably his greatest contribution came from his groundbreaking work in tissue culture, of which he is regarded as the founding father (Federoff 1987). Together with his equally creative work on embryonic transplantation, he spearheaded research charting the development of peripheral nerve growth and regeneration, pivotal early work that he communicated in significant part via The Anatomical Record (Harrison 1907a, 1907b, 1907c, 1908, 1912; Harrison et al. 1907.) His observations and use of experimental studies in embryology by use of tissue culture not only provided unprecedented insights into mechanisms of peripheral nerve growth, but also set the stage for the field of stem cell biology. His achievements in this area alone prompted the Nobel Committee to vote to give him the Prize in 1917; however, for reasons that have never been completely clear, they decided not to grant a prize that year (Nichols 1961). Most have seen this as a continuation of the nongranting of the prize in Physiology or Medicine due to World War I (no prizes in 1915–1918); however, the Committee was strong in their recommendation that Harrison receive it. The reasons suggested for his nonreceipt of the prize have been murky and lost to interpretations and time. Some, for example, have attributed this egregious omission to more nefarious underpinnings, such as Harrison's supposed partiality toward Germany during the war years (he did have both a German wife and a number of German professors in his laboratories at Yale, so unsubstantiated rumors abounded). Although he was nominated again and again, and for other accomplishments such as pioneering studies on asymmetry (also appearing in The Anatomical Record; Harrison 1916, 1917) he was passed over (he lost out in 1933, for example, to T. H. Morgan and his insightful work on genetics). The horrific oversight notwithstanding (although no scientific son or daughter of Yale will ever let this go), Harrison's pioneering work in tissue culture allowed the nascent field of peripheral nerve biology and regeneration to be robustly hatched. As noted, his influence in the anatomical world (he was a President of the American Association of Anatomists, the parent organization of The Anatomical Record, in 1912) and in the zoological realm (he was Editor-in-Chief of the Journal of Experimental Zoology) was enormous, and remains to this day. Of the many great men and women who have published in our journal, the quiet, scholarly genius from the Osborne Laboratories in New Haven surely has a reserved place of honor. It is difficult to supersede one of the all-time scientific greats; nevertheless, many luminaries followed who published their findings on both comparative anatomy and developmental growth and/or regeneration of peripheral nerves and components in The Anatomical Record. For example, C. Judson Herrick (1910), the long-standing Editor of the Journal of Comparative Neurology and a founder of neuroanatomy in the United States published his evolutionary observations on relations of the central to peripheral nervous systems in The Anatomical Record in 1910. The noted anatomist and experimental embryologist, Samuel R. Detwiler, similarly published in The Anatomical Record. Detwiler was a student of Harrison's at Yale and, like him, became President of the American Association of Anatomists. He published observations on how nerve cells proliferate after grafting (Detwiler 1924) following up on his mentor's landmark work. Other studies of note also appeared in our journal in these early years: Grodinsky published his findings on experimental manipulation of sacral nerves in 1928 (Grodinsky 1928). Sullivan and Mortensen advanced their new methods of peripheral nerve visualization (Sullivan and Mortensen 1934). The renowned primatologist Sir Solly Zuckerman (later, Baron Zuckerman; an anatomist who did pretty well!) published observations on sympathetic components of peripheral nerves in rhesus macaques (Zuckerman and Burr, 1934) (while his "day job" was as a well-respected anatomist, Sir Solly actually wore many hats; indeed, being an advisor to the Allies on bombing strategy during World War II; all things considered, he was probably the most influential anatomist of the 20th century!). David Bodian, another 20th century anatomical luminary, published his early findings on new methods of peripheral nerve staining in The Anatomical Record (Bodian 1935). Bodian cemented his place in science by combining neuroanatomical research with study of pathogenesis of polio that helped lay the groundwork for the eventual development of polio vaccines. Bodian was elected to numerous honorific societies and was, like Harrison, a President of the American Association of Anatomists (in 1972). Shortly after Bodian, reportage appeared by the greatly respected Johns Hopkins psychiatrist/neuroanatomist Orthello R. Langworthy (fascinating name) on changes in muscle after injury to peripheral innervation (Langworthy and Kolb 1938). Also in this great chain we cannot overlook the outstanding anatomist Paul Alfred Weiss. Weiss' main focus was specifically regeneration of nerves, and he came to the United States in the 1930s to do a Fellowship under Harrison at Yale where he could perfect his tissue culture techniques. He published his findings on experimental studies of the motor effects of connecting sensory nerves to muscles (Weiss 1934) and, later, regeneration of the lateral line of Amblyostoma (Weiss and Cummings 1943). Weiss did crucial work with the US government during World War II on nerve injury. He was chosen as one of the first professors at the Rockefeller University when it was founded in 1954 and received the National Medal of Science from President Carter in 1979. Looking at the years after the war, we find studies by Hiscoe on differences between normal and regenerated fibers in peripheral nerves (Hiscoe 1947); Bueker and Meyers (1951) in assessing the maturity of peripheral nerves as a factor in regeneration; detailed assessment of the fine structure of peripheral nerve fibers by Hess and Lansing (1953). In 1954, we find a contribution on the effects of peripheral nerve section on metabolic responses of brown adipose tissue in rats by two Titans of the scientific cosmos: Sidman and Fawcett (1954). These are names well known to anatomists as their individual contributions had enormous influence in the years following their work. Both spent much of their careers at Harvard, where Sidman gained fame as a consummate neurobiologist and Fawcett (a President of the American Association of Anatomists in 1966) as one of the great histologists of the century and amongst the founders and promoters of electron microscopy. The advent of electron microscopy helped foster in an era of the application of many new visualization modalities into both the underlying anatomy and regeneration of peripheral nerves, many of which followed the path of their august predecessors and subsequently came to light in The Anatomical Record. Indeed, detailing all of the related studies of the last 60 years would entail a small monograph, so here our overview will end. Hopefully this glimpse into reportage in our journal over roughly its first 50 years will give insight into the relationship The Anatomical Record has had with the study of peripheral nerves and their regeneration. As is well articulated by the accompanying piece by our Associate Editor, José Luis Trejo (Trejo 2018, this issue), the numbers and scope of peripheral nerve injuries are enormous, and a devastating clinical problem for the many thousands afflicted. The biological and psychological trauma to those who suffer from peripheral nerve injury cannot be overstated. The answer to restoration of function and improvement in quality of life will only come as investigations peel back the mysteries that surround the nature of growth and regeneration. For those with peripheral nerve injury the problems caused are anything but peripheral; they are at the center of their world. We are proud that The Anatomical Record continues our great tradition of uncovering the secrets within these most central, peripheral nerves. Jeffrey T. Laitman1 and Kurt H. Albertine2 1Center for Anatomy and Functional Morphology, Mount Sinai School of Medicine, New York, New York, and 2Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah