My perfect day awaits. They're all gone; even the dog is out. My son has been dispatched to get the appropriate, required libations and comestibles, and my best buddies will be here shortly to watch with me as our beloved New York Yankees trounce and humiliate the hated Boston Red Sox (yeah, yeah, I know the Sox have won some things recently; just count the rings, bean-boys). The phone is off the hook and even my cell phone has been banished to another room. Nirvana.
“Dad,” a shattering voice rips uninvited into my mind. “DAD, can you hear me?” (Where did she come from?). “Dad, turn down the volume and listen to me” (for discussions on age-related hearing loss see previous Anatomical Record special issue, Friedland,2006) “I have an important question.” (Why is my 14-year-old daughter asking me an important question? She never asks me “important” questions. I don't think in 14 years she has ever asked me anything important. Oh, God, I hope it's not the sex question! Where's my psychiatrist wife when I need her!”) “In school, we had this discussion in Physics about the meaning of “space”, and I was wondering: What's inside an “empty box”? (What—my 14 year old is asking me about the existential meaning of “emptiness”? What goes on in these schools nowadays? Teach them how to add or the number of planets—how many are there now, anyway?—not ponder deep philosophical issues). “I mean,” she prods further as her eyes sear into me, “empty isn't really empty, right?” (Oh, God! Why is this happening? I hated this stuff in school. I still remember trembling and being lost when my teacher asked us the “meaning” of the “white whale” in Moby Dick. To me it was a whale, just a big, angry, white whale! Who knew it had meaning? I hate things with meaning. That's why I'm an anatomist. I cut up dead things and see where the parts are. I don't do “deep” questions. Oh, Lord, my little one will find out my secret: I have the philosophical ability of a newt. She will know her dad is shallow, “empty” like the subject of her question. My cover will be blown. My…) “Dad. Hey dad” she shouts, “never mind. Gotta go. My friends are picking me up; we're going to town. Can I have money?”
As I sat shaking, recovering from this unsettling assault to my fragile psyche, my mind—at least the few neurons still functioning at this point—shot back to a similar discussion some years back. “Dr. Laitman,” asked Sam Márquez, at the time one of my sharpest (and most polite) graduate students, “might you have a moment for me?” (I was only too happy to put to the side my latest budget reductions from the Dean to speak with a student, let alone one of my best). “I just wanted to tell you that I really enjoyed your lecture on the skull” (at least someone was listening) “but there were some things that were not really clear to me from your talk” (great, another critic is born; get in-line with my last grant reviewers). “I was confused about the sinuses, the “hollows”, that you were describing, the ones around the nose. What did you mean when you said they were “air” containing spaces? What “type” of air? They're not really “empty”, are they? I mean they must have contents of some sort. “Air” inside the head cannot be the same as “air” outside the head, can it? So, what really is “in” those spaces? Also, I know you said they were outgrowths of the different bones, but when do they appear developmentally, and are the patterns always the same for every sinus, and for everyone, and between men and women, and for other anthropoids, and what about ancestral hominids? And, the BIG issues you did not discuss at all: what do they do, why are they there? Also…” (Oy! Why is he asking all this? I'm paying a small fortune for him to study the epiglottis of some nice terrestrial animal, why is he going on about these awful little spaces that people have been arguing about forever and nobody seems to know anything about anyway.) “Uh, Sam” I say in my best very busy Professor voice, “I have to respond to the Dean on a number of important budget issues, so why don't we pick this thread up at another time” (like, when I retire; go away and get back to some nice larynx).
Alas, like so many of my students, Sam Márquez did not take my advice. He neither went away nor ceased bothering me with his incessant queries into the strange hollows and their myriad of connections that so attracted his wandering and inquisitive mind. Indeed, the now Dr. Márquez, was gradually becoming one of that compulsively driven group of internal body spelunkers, determined to decipher the seemingly incomprehensible—and yet, ever fascinating—world of the paranasal sinuses. An insight into that extraordinary realm can be seen in this month's special issue of The Anatomical Record, “The Paranasal Sinuses: The Last Frontier in Craniofacial Biology”, guest edited by Samuel Márquez (2008, this issue). In this issue, he has garnered a gaggle of like-minded souls who, like him, have heard the siren's call of these mysterious hollows. With his background in both comparative anatomy and primate and human evolution, Márquez has put forth an issue that explores the sinuses from the vantage point of understanding both their basic biology and their place in the vertebrate world, both through comparative and evolutionary lenses. The collection of articles in this issue conveys at once the complexity of these seemingly inscrutable sinuses and the excitement in the hunt to uncover their functions and histories.
To understand fully the paranasal sinuses, and investigations into them, it is important to begin with a basic appreciation of the common denominator: very little is clear about them, and equally little is fully agreed upon by those who investigate them. Let's begin with the area of agreement: they're in the head. Good. Next, they are embryonic outgrowths of portions of the nasal region sensu latu, but it is not always clear which sinuses come from where. When you get beyond those mammals that pay taxes, embryological relationships get even murkier. Everything else is often debated. And I mean everything. Indeed, the title of a 1969 article on the sinuses was, “Eighteen hundred years of controversy” (Blanton and Biggs,1969). Interestingly, this article itself appears to have been controversial, with the journal inserting an editorial note that some editors wanted it published and others not! Seems, one can't even publish on the topic without there being disagreement.
So, what's so controversial? Two issues are inextricably entwined here: what the sinuses do and who said what they do (or, who said who said what they do) and when did they say it (or draw it, imply it, think about it…). Clear? Although the first area regarding paranasal sinus function is of greatest importance for us as biologists, the history of their “discovery” and the involvement of those who discovered them are intriguing as well, and gives insight into the confusing millennia that have ensued. Let's begin there.
Who first “discovered” the sinuses? Cognizance of the sinuses probably first occurred some one to two million years before the present on the African savannas when “Ugh” hit “Bugh” square on the face with a rock and noticed that the nose and cheek area above the teeth caved in quicker than hitting him on top of the head. As writing was not yet around, this newfound knowledge was assuredly passed down by oral tradition, much as I told my own son when he was a boy that should he ever be forced to defend himself he should hit the other guy hard and square in the nose, that is, the “soft” part of the face. (My peace-loving, suburban-raised son looked at me—his Brooklyn-bred father—in abject horror and proceeded to tell his mother that I'm teaching him to kill people). Although early physicians/anatomists clearly must have recognized the odd nature of these spaces, it is unclear when they were first described or appreciated as to their communications. Clearly, the ancient Egyptians must have known something of sinusal anatomy as their removal of the brains during the mummification process apparently took a sinonasal route, and posterior approaches to the orbit proceeded through the lamina papyracea/ ethmoid route (Babin et al., 1990; Stoney,1991). No formal descriptions of the sinuses appear, however, in any of the ancient Egyptian treatises—arguably the earliest texts devoted to medical issues—such as the famed Papyrus Ebers (or Ebers Papyrus) dated around 1550 BC, the Smith Papyrus dated around 1600 BC, or the slightly younger Brugsch Papyrus of 1300 BC (see Stoney et al.,1991).
Although anatomical investigation in the Greek world advanced, it is unclear, and disputed, as to whether Alcmaeon (5th Century BC), sometimes regarded as the “first” Greek anatomist, or the philosopher/physician Empedocles who followed him, were aware of sinusal structure, although it has been suggested that the latter may have described features of them in one of his works (Stoney et al.,1991). It is unclear as to whether or not Galen in his magnus opus De Usu Partium (Galen, 175 AD; see the translation by May, 1968) recognized the sinuses as such. Galen does make frequent mention of the “porous” nature or the “porosity” of some bones, and does speak about the “spongy” nature of the ethmoid (he preferred calling it the “spongoid” bone—obviously didn't catch on; see Bowman,1988), but, at least by my readings of his translated works, there does not appear any clear comprehension of the nature or shared similarities of the sinuses. To some extent, this is rather an interesting omission, as Galen goes to great lengths to describe “hard” bones or those that have or do not have marrow (see, particularly, Book XI, De Usu Partium) in his discussions of the strength of bones, even giving examples from different animals. In addition, he often discusses the nature of the nose and its primacy as the route for breathing over the oral pathway, as well as discussing the idea of “brain breathing”, that is, the brain receiving its direct air source through nasal channels. He thus must have been aware of the environs and communications of the nose. The glaring absence in his recognition of the sinuses has been noted by others as well (e.g., Wright,1914) and raises some questions in my mind as to whether Galen's descriptions may have been based more upon nonhuman sources that may exhibit less or differing pneumatization of these areas than that clearly apparent in adult humans. Pigs, however, Galen's usual subjects, also exhibit extensive sinusal pneumatization, so he would have had to come in contact with this pattern in these animals as well. As they say, a puzzlement! Whatever the basis for his not recognizing the sinuses as such, I find it most surprising.
Credit for putting the sinuses, notably the maxillary sinus, into public consciousness is usually given to the English surgeon Nathaniel Highmore (1651) and, indeed, this sinus is often referred to as “the Antrum of Highmore” in his honor. Although Highmore has usually been highlighted, the great Leonardo da Vinci considerably predated him in describing and beautifully illustrating both the maxillary and frontal sinuses (O'Malley and Saunders,1982; see also discussions in Imperatori,1941; Blanton and Biggs, 1962; Stoney et al.,1991; Harle,1992). Da Vinci's drawings and notes, which may have been made as early as 1489, were not, however, published or widely known about in his lifetime. Indeed, these drawings appear to have had a remarkable and mysterious life of their own, someway or other eventually finding their way by the late 17th century to the Royal Library at Windsor Castle. Various morsels of these magnificent illustrations appear to have emerged in dribs and drabs over the next few centuries with some, unfortunately, apparently being lost over time (see O'Malley and Saunders,1982 for complete discussion). Fortunately for sinus aficionados, Leonardo's incomparable vision of these structures has been amongst those that have survived.
Prior to the high-water mark of Highmore, a number of anatomical luminaries enlightened the world about sinuses in considerable ways. For example, Berangario da Carpi appears to have been the first to describe the sphenoid sinus (1522); Vesalius himself, “the father of modern anatomy,” described the maxillary sinus in the great Fabrica (1543) and may have been the first to note that they contained “air” (see Blanton and Biggs,1969); and Vesalius' dutiful student Fallopius further described the cavities (1561), and his observations that they were not present in the skulls of newborn humans was possibly the first developmental observations regarding the significant age-related appearance of these structures.
Two figures, however, stand pre-eminent in the hunt to understand these sacred hollows: Nathaniel Highmore and Emil Zuckerkandl. The observations of the aforementioned Nathaniel Highmore, indeed, stand alone as the branch-point for clinical recognition about the sinuses in general and the maxillary sinus in particular. His detailed descriptions and illustrations in his treatise, Corporis humani disquisitio anatomica (Highmore,1651), of the sinus and of a case of suppurative maxillary sinusitis and its course in a patient with the affliction, is a recognized landmark in head and neck medicine. All subsequent anatomical and medical observations must by need refer to the door opened by Highmore. In a similar vein, the prodigious work by the incomparable Austrian anatomist Emil Zuckerkandl in 1882 (Zuckerkandl, 1882) set a standard for assessing the anatomy and pathology of the sinuses that is the basis for modern understanding of their structure. Indeed, his work was of such a meticulous nature, rendered in such exquisite detail—and of such continuing value to practicing surgeons today—that he was anointed as the “father of modern sinus anatomy” by William Lawson (1994) of The Mount Sinai Hospital, himself one of the undisputed giants of modern sinus surgery. Although many other valuable contributions have been made since Zuckerkandl—most notably by the prolific and energetic otolaryngologist Sir Victor Negus (1958) in his comparative review of the nose and sinuses—it was the “Big Two” of Highmore and Zuckerkandl who set the template for our modern understanding of, and—particularly important for us frequently afflicted humans—surgical approaches to, the sinuses.
Although the road to “discovering” the sinuses was sinuous at best, trying to decipher their functions, let alone their evolutionary history, has been an extraordinary meshwork of science, pseudoscience, and just plain conjecture. Apparently, the earliest arguments were over what was “in” the sinuses, with sides being drawn between those supporting “air” as advanced by Highmore and his clan, and those favoring the idea that there was an assortment of “humors,” some of which may have drained the brain of “evil spirits” through the mucous of the sinuses and nose (see Márquez,2008; Schaeffer, 1920; Stammberger,1989). While the evil humor theory seems to have lost supporters (although, having teenagers—particularly that aforementioned tormenting daughter—I'm not so convinced that the evil spirit theory is so off-base) most of the others advanced over the millennia are still out there. Theories on function, many addressed by articles in this issue, range from those suggesting assorted respiratory system related roles (e.g., air circulation relating to olfaction; humidification or warming of air; voice and resonance), to those suggesting biomechanical functions (e.g., lightening of the bones for head balance; allowing for developmental features of facial growth and differentiation; providing architectural features related to masticatory forces), to those that see the sinuses as evolutionary dead or “residual” spaces with no real function, to those that meld ideas from columns A, B, or C.
Although finding a definitive answer to the age-old question of “what do sinuses do?” may remain elusive, this special issue offers an unsurpassed view of the state-of-the science and understanding of the current nature of investigations into their world. Márquez has put together a tantalizing smorgasbord of hypothesis-driven research and scholarly reviews that encompass the key issues, central problems, ongoing arguments, and new understandings coupled with the dynamism of new techniques and technologies—particularly the power of modern imaging technology—that those in the trenches today employ.
Given Márquez' own interests and background in comparative and evolutionary studies, he has recruited a number of articles in these areas, and the range and observations that are presented are nothing short of fascinating. The cranial world of the great dinosaurs (the most interesting ones, the toothy meat-eaters; sorry brontos and vegans) are explored and unearthed and compared to living archosaurian relatives (crocodilians and birds; I respect New York pigeons much more now) with some most surprising and novel findings. Our sea faring “sinus-less” cetacean relatives are put under a watery eye with questions raised as to what structures may have taken over sinus function and when this may have occurred evolutionarily. Our own nonhuman primate relatives are the subjects of a number of articles, with aspects of their biology being explored in taxa ranging from little South American monkeys to the Great Apes, with tree-loads of Old World monkeys of all types swinging through many articles. And, if paleo-primates or fossil human ancestors are to your liking, then you will have a feast, as the world of the nose and sinuses are explored from examinations of fossil primates from the Miocene of South Africa to studies on human ancestors, including the ever-intriguing Neanderthals.
The application of hypothesis-driven approaches using model systems is a conspicuous thread that weaves through many of the studies in the issue. Indeed, a number of these innovative studies use such modeling approaches to get a clearer picture of the roles the various sinuses play, or the underpinnings of their distinctive morphologies. Again, nonhuman primates are featured prominently as the models—often as “natural experiments”—to test hypotheses relating to whether shape and size are related to biomechanical/architectural forces or other drivers, such as respiratory-related requirements. The exciting role of detailed mathematical modeling is also explored, with the new and valuable insights afforded proving most clearly the power of this approach in shedding light on the old questions.
New findings on aspects of the developmental anatomy, physiology, and pathology as it relates to clinical treatment, are presented in both new studies and reviews. Particularly impressive are those clinically related investigations that explore and assess the incredible power of imaging technologies—such as recent advances in CT, MR or PET scanning—that allow for the understanding of sinusal development, variation, and disease at a level previously unattainable by more traditional radiographic methods. While new aspects of the structural anatomy are revealed, detailed review of the role of nitric oxide production and its interplay with the physiological processes places the integral nature of these sinuses in crystal-clear perspective.
Although a Rosetta Stone for deciphering the world of the sinuses is unlikely to be found, the combination of insightful approaches and new methodologies and technologies may provide a close second. Some of the seemingly unattainable mysteries of these perplexing “empty” spaces may soon be broached. Indeed, an understanding of arguably the last frontier in craniofacial biology, the world of these hallowed hollows, may not be as far off as it once seemed.
“Dad, I'm back,” shouts a piercing, most unwelcome voice. “DAD, LISTEN! Back to my question” (Oh, no! Not her and her questions again!), “so, what's inside an empty box?” “You know, sweetheart,” I say in my caring, insightful, paternal-wisdom voice “just so happens that my former student Sam Márquez is a world expert on this stuff. Give him a call; I know he'd be glad to explain this all to you in great detail” (Ahh. Now, back to the game…)