A Century of Progress

Evolution of Research in Otolaryngology- Head and Neck Surgery Over the Past Century

James B. Snow, Jr., MD Director, National Institute on Deafness and Other Communication Disorders

major impetus for march in otolaryngology-head and neck surgery was, and continues to be, the desire to decipher A the mysterious code of biology to improve life through med-

ical intervention. Throughout history, curious and dedicatedscientists and physicians have sei7d opportunities using the technology of the time to advance knowledge of normal and disordered processes of the ear, n w , and throat and the head and neck in general to provide the foundation for the methods of evaluation and therapy available today, It is appropriate to paw and look back at what has been accom- plished in the past century and how it was done. The 100th anniver- saries of the ~ Y N C O S C O P E and the Triological Society, along with the approaching2lst century, give us ample reason for such reflection.

We m in the midst of an exciting period of accelerating discov- ery. The m e auld have been said 100 years ago. The turn of the cen- tury was a provocative time for physicians and scientists devoted to the e m , nose, and throat. Anatomical research had plateauedwith the el- egance of the studies of Retzius.’ The experimental study of function was beginning as exemplified by the 1914 Nobel Laureate Robert BMny’s contributions to vestibular psychophysics.2 His application of precise stimuli and measurement of the responses led to the develop- ment of the quantified caloric and rotational tests that, although modified, have withstood the test of time and have been embellished with electrophysiologic contributions such as electronystagmography. With similar precision, he developed galvanic and pneumatic fistula tests. Psychophysical advances occurred in hearing with the advent of theelectronic audiometer in the 1930s by Fowler3 and associates. With this technology, the patterns of hearing loss were identified and the phenomenon of auditory recruitment became aclinical tool for differ- entiating sensory from neural hearing impairment. Other special au- diometric tests, such as the short increment sensitivity index, tone de-

cay and automatic audiometry, alongwith tympanometry and acous- tic reflex decay culminated in adiagnostic battery for determining the site of the auditory lesion. Although this battery has been largely sup- planted by electrophysiologic developments, it improved the under- standing of the pathophysiology of sensorineural hearing impair- ment. Advances in the psychophysics of the sense of smell by Zwaardemake1-4 and in taste by Pfahann5 depended less on new technology as in hearing but on application of the principles of psy- chophysicsdeveloped in the other senses.

New strategies and tools emerged in the early decades of the 20th century and had a major impact on clinical practice. General as well as local anesthesia had become relatively safe, and aseptic surgery in- troduced by Halsted had made possible new surgical approaches. In the 1920s and 193Os, mastoid surgery for acute mastoiditis and chron- ic otitis media was highly successful. Attempts at surgery for otosclem- sis and laryngeal carcinoma met with mixed success. Edison’s 1879 invention of the i n c a n h n t lamp facilitated illumination and in- spection of the interior of the respiratory and alimentary tracb.Jack- son and others refined and expanded the usefulness of endoscopy, and this refinement has continued throughout the century with a dramat- ic high point being Ikeda’s development of the flexible endoscope. Rontgen’s discovery of the x-ray in 1895 initiated the development of fantastic diagnostic capabilities with each succeeding one being more breathtaking. The discovery of radium by the Curies in 1898 offered new therapy for individualswith malignant neoplasms that continues to evolve.

Many surgical failures in the 1940scauld be attributed to the in- ability to control infection. The introductions of sulfonamides in the 193Os, penicillin in the 194os, and amultitudeof antibiotics thereafter as well as the magnification and illumination of the operation micro- scope validated many earlier surgical concepts including tym- panoplasty, stapededomy, and safe vestibular schwannoma excision.

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Hy the end of tlie first quarter of the 20th century, the ability to control and measure minute amounts of electricity led to an era in wliich electrophysiology was the preeminent source of new informa- tion. I n hewing. Wever and Bra? led the way in the 1930s with mea- surement of the inner ear bicelectric phenomena asssociated with au- dition. ’fhe cochlear microphonic as well s the more fundamental endoctdilear potential and eighth nerve action potentials captured the attention of a generation of young biologist$. Wide field and finally singlecell measurements in thecentral auditory pathway led to multi- ple clinical applications including electrocochleography, brainstem- evoked responses, electroneuronography, and the greatest clinical achievement of the century, cochlear implantation. Implants with niultiple channels and improved speech processing now benefit chil- dren and adults who are deaf as well as adults who receive marginal benefit from hearing aids.

As the electrophysiologists were developing a wealth of informa- tion in the second half of the 20th century, two other research strate- gies were providing startling answers and creating new questions. The 1961 Nobel 1;aureate Georgvon Bikhy7 ushered in the micromechan- ical trendin auditoryresemh in thelate 1920swith hisseriesofexpr- irnents that describe the physical mechanisms of stimulation in the cochle:i. Kemp discovered otoacoustic emissions in the 1970s, and Brownell’s demonstration of outer hair cell motility in the 1980s brought micromechanical investigation to a stunning climax with the realization that this mechanism contributes to theexquisitesensi- tivity and frequency specificity of the inner ear. As von @k&y contin- ued his experiments, the transmission and subsequent scanningelec- tron microscopes burst on the scene, leading all to inquire what are these newly seen structures and ofwhat are they conipased?

With thediscoveryof thestructureof DNA in the 1950s by Watson m d Crick, the answers to the molecular questions were soon to follow. By the 197Os, tlie molecular biology revolution was beginning and in the 1980s it was in full swing. Research in otolaryngology-head and neck surgery has also entered the molecular biology era. Although the psychophysical, micromechanical, and electrophysiological ap- proaches have yielded extraordinarily important information about normal processes and the pathophysiology of diseases and disorders and will continue to do so, nothing provides hard information, about the essence of disease and with which the disease can be controlled, like molecular biology. For the first time, information is forthcoming that has a high probability of being used to modify the pathogenesis of the disease directly.

For example, a multitude of mutant genes responsible for hered-

itary hearing impairment have been hxated, as have genes involved in the normal development and function of the inner ear. Linkage studies have already identified dominant, recessive, and X-linked genes for various forms of nonsyndromic hearing impairment as well as many genes responsible for the syndromes of hereditary hearing impair- ment. As these genes are cloned and sequenced and the functions of their natural alleles are determined, many long-standing puizles and some not yet conceived will be solved. For example, it is now apparent that the allele of one of the genes responsible for one type of Waarden- burg’s syndrome control tlie migration of progenitors of melanocytes from the neural crest to the stria vascularis. In an aninial model of Waardenburg’s syndrome, the absence of melanmocytes in the stria is associated with reduction of the endocochlear potential.

In another puzzle-ending example from the olfactory system, the allele for the gene responsible for Kallmann’s syndrome is required for the migration of olfactory receptor neurons to the olfactory neu- roepithelium and neurons synthesizing gonadotropin-releasing hor- mone to the hypothalamus from the olfactory placcde. Buck and Ax- el’s* discovery in 1991 of an enormous family of olfactory receptor genes demonstrates the evolutionary importance of the sense of smell and provides a provisional explanation of specific anosmias. Their landmark discovery has accelerated olfactory research as well as con- tributed to a new general biologic understanding in that the number of genes devoted to olfaction is similar to the number devoted to the immune system.

The techniques of molecular biology promise to change medi- cine as we know it. Research is addingcredence to the theory that most if not all disorders of human communication are genetically deter- mined. Recent evidence suggests that many disorders of human com- munication that have been attributed to environmental factors have, in fact, a genetic basis. For example, Fischel-Ghodsianq haisdiscovered a mitochondria1 mutation predisposing certain Asian families to un- usual susceptibility to aminoglycoside ototoxicity. Variation i n indi- vidual and familial susceptibility to noise-induced hearing loss and presbycusis suggests that a genetic predisposition may exist in these disorders as well. Determination of the molecular mechanisms oper- ating in these forms of hearing impairment as well as other commu- nication disorders such as autism, stuttering, and dyslexia is well un- derway. With this kind of information, a new era of molecular preventive medicine will evolve.

As Niels b h r said with a Yogiesque twist, “Prediction is very un- certain, particularly about the future”; therefore, I will limit mine to one paragraph. The specialty of medical genetics as such will disap-

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pear because all physicians will become geneticists. The scientificdis- ciplinesofpsychophysics andelectrophysiology will be hyperenergized to determine the function of all of the genes and gene products discov- ered by the molecular geneticists. Physicians will apply the knowledge of molecular biology to the prevention and control of disease processes through substitution, restoration, and gene transfer therapy. With the

advent of the National Institute on Deafness and Other Communica- tion Disorders, fundamental and applied science related to otolaryn- gology-head and neck surgery will enter the new millennium with financial support equitable to that of the other disciplines of medicine, and individuals with disorders of human communication will benefit from the full promise of molecular medicine.

BIBLIOGRAPHY

1. Retzius MG. Das GehBrorpn der Wirlxtlthiere. In: Mwpbologisch- bistdogid~e Studien (Vol. 1 ). Stoc.kliolm: Samson CG Wallin: 1881.

2. BPdny H. Ilntersuchungen ulwr den vom Vestihularappamt des Ohres reflectorisch ausgclosten rhythinischm Nystagtiius und wine kegleiterscheinungen. Mschr Ohrtwhdk 1906;40: 1%.

3. Fowler EP. Marked deafened areas in normal cars. Arch Ottdrcryn-

4. Zwaardemker H. The sense o f smell. Asta Olo-frrryngd 1027;ll:

5. P h f f m n n C. nie afferent code for sensory quality. Am Psy~bol.

gd. 1928;8:15 I - 155 .

3 1 5 .

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6. Wever EG, Bray CW. Action currents in the auditory nerve in re- spon.w to acoustic stiniuhion. PmxNutl AcndSci. 1930: 16:344- 350.

7. von Wkesy G. hpt iment s in Heuring. New Yiirk:hlcC;~iw-Hill: 1960.

8. Buck L, Axel R. A novel multigene family n u y enc tde tdorant rc- ceptors, a molecular basis for odor recognition. <XI. 1991:65: 175-187.

9. Fischel-Ghodsian N, ei :iI. Mitochondria1 rihosonial HNA gene mu- tation in a patient with sporadic aminoglycosirle otoloxicity. .4m J Otolatpgd. 1993;14:399-403.

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