John T. Connell

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treatment on human nasal mediator release after antigen challenge. J Clin Invest 1987;80:957-61. Bascom R, Wachs M, Naclerio RM, Pipkorn U, Galli SJ, Lichtenstein LM. Basophil influx occurs after nasal antigen challenge: effects of topical corticosteroid pretreatment. J Allergy Clin Immunol 1988;81:580-9. Iliopoulos O, Baroody FM, Naclerio RM, Bochner BS, KageySobotka A, Lichtenstein LM. Histamine-containing cells obtained from the nose hours after antigen challenge have functional and phenotypic characteristics of basophils. J Immunol 1992;148:2223-8. Pipkorn U, Enerback L. Nasal mucosal mast cells and histamine in hay fever. Effect of topical glucocorticoid treatment. Int Arch Allergy Appl Immunol 1987;84:123-8. Wachs M, Proud D, Lichtenstein LM, Kagey-Sobotka A, Norman PS, Naclerio RM. Observations on the pathogenesis of nasal priming. J Allergy Clin Immunol 1989;84:492-501. Gronborg H, Borum P, Mygind N. Histamine and methacholine do not increase nasal reactivity. Clin Allergy 1986;16:597-602. Walden SM, Proud D, Lichtenstein LM, Kagey-Sobotka A, Naclerio RM. Antigen-provoked increase in histamine reactivity. Observations on mechanisms. Am Rev Respir Dis 1991;144:642-8. Juliusson S, Bende M. Priming effect of a birch pollen season studied with laser Doppler flowmetry in patients with allergic rhinitis. Clin Allergy 1988;18:615-8. Andersson M, von Kogerer B, Andersson P, Pipkorn U. Allergeninduced nasal hyperreactivity appears unrelated to the size of the nasal and dermal immediate allergic reaction. Allergy 1987;42:631-7. Bousquet J, Lebel B, Dhivert H, Bataille Y, Martinot B, Michel FB. Nasal challenge with pollen grains, skin-prick tests and specific IgE in patients with grass pollen allergy. Clin Allergy 1987;17:529-36. Iliopoulos O, Proud D, Adkinson NF Jr, Norman PS, KageySobotka A, Lichtenstein LM, et al. Relationship between the early, late, and rechallenge reaction to nasal challenge with antigen: observations on the role of inflammatory mediators and cells. J Allergy Clin Immunol 1990;86:851-61. Ciprandi G, Ricca V, Landi M, Passalacqua G, Bagnasco M, Canonica GW. Allergen-specific nasal challenge: response kinetics of clinical and inflammatory events to rechallenge. Int Arch Allergy Immunol 1998;115:157-61. Koh YY, Choi JW, Lee MH, Sun YH, Lee SI, Lee SY, et al. A preceding airway reaction to one allergen may lead to priming of the airway responses to another allergen. Allergy 1997;52:284-92. Bousquet J, Hejjaoui A, Becker WM, Cour P, Chanal I, Lebel B. Clinical and immunologic reactivity of patients allergic to grass pollens and to multiple pollen species. I. Clinical and immunologic characteristics. J Allergy Clin Immunol 1991;87:737-46. Saini S, Bloom DC, Bieneman A, Vasagar K, Togias A, Schroeder J. Systemic effects of allergen exposure on blood basophil IL-13 secretion and FcepsilonRIbeta. J Allergy Clin Immunol 2004;114: 768-74. Pipkorn U, Proud D, Lichtenstein LM, Kagey-Sobotka A, Norman PS, Naclerio RM. Inhibition of mediator release in allergic rhinitis by pretreatment with topical glucocorticosteroids. N Engl J Med 1987;316:1506-10. Iliopoulos O, Proud D, Adkinson NF Jr, Creticos PS, Norman PS, Kagey-Sobotka A, et al. Effects of immunotherapy on the early, late, and rechallenge nasal reaction to provocation with allergen: changes in inflammatory mediators and cells. J Allergy Clin Immunol 1991;87:855-66. Received for publication April 5, 2006; accepted for publication April 6, 2006. Available online May 22, 2006.

JOHN T. CONNELL I have known Jack Connell (Fig 1) since his early years as an attending and research worker at the Roosevelt Hospital in the early 1960s and have greatly

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FIG 1. John T. Connell circa 1970.

admired him through the years for his deceptively simple and elegant research. It reflects the intelligence, ingenuity, and critical faculties that led to the remarkable demonstration of the so-called priming effect of repeated exposure to pollen, which is being recognized in these pages.1-3 After their publication, the late Rockefeller University Professor Merrill Chase (personal communication), well known as a demanding scientist, described the work as ‘‘awesome and good science.’’ Jack, a quiet and private person, agreed to several meetings and made private papers available for this biographic sketch, for which I thank him. He was born in a small Pennsylvania town on August 3, 1926, and spent his formative years in Claritin, Pennsylvania. His father, a bus driver, was able to tear down and rebuild automobile engines, and this mechanical ability, which was passed down to Jack, played an important role in his life and in his future research. The family was of very modest means (‘‘we were poor but didn’t know it’’), and during his high school years, he always had a part-time job to help out. In his senior year he worked on the night shift at an oil refinery from midnight to 8 AM for 25 cents an hour, sleeping only 4 hours a day, despite which he graduated as an honor student. In 1943, during World War II, he volunteered for military service as a naval air cadet and was sent to Ursinus College, a small school near Philadelphia, majoring in naval science. During his first year, he became friendly with a classmate, who introduced him to her father, a Philadelphia ophthalmologist, who befriended him and encouraged him to consider medicine as a career. He received permission from the

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Navy to take the required premedical courses, with the stipulation that this would be in addition to his engineering courses. He completed this very heavy schedule creditably, while also compiling a winning record as a pitcher on the varsity baseball team. After victory in Europe, he was transferred to Villanova College for a semester, until Japan surrendered, when he was discharged from the Navy and continued as a Villanova student, receiving a Bachelor of Science degree in 1947. He then went on to the University of Pennsylvania Medical School, graduating in 1951. During his first year, he married a classmate, and after graduation, a year of rotating internship, and a year of residency in pathology, he and his wife established a small-town general practice in Blue Hill, Maine, where they remained for 5 years. Jack’s reminiscences of those years could fill a book, but suffice it to say they were among the happiest years of his life. He enjoyed the variety of patients and earned the regard of his colleagues, evidenced by being elected president of the county medical society his fifth year in Blue Hill. Although the Hancock County Medical Society in 1957 consisted of only 10 members, Jack recalls that the vote was unanimous. Because of his wife’s interest in specializing in gynecology and his interest in internal medicine, they returned to Philadelphia in 1958, where he became a resident in internal medicine at the Graduate Hospital of the University of Pennsylvania. During this time, he came to know Dr Merle Miller, a prominent Philadelphia allergist and former officer in the American Academy of Allergy, who encouraged him to enter the field of allergy and clinical immunology and recommended the training program at Roosevelt Hospital in New York City. He was interviewed and accepted for the program by its director, Dr Robert Cooke, but by the time he entered the program in 1960, Dr Cooke had died, and Dr William Sherman, a leading allergist and past President of the American Academy of Allergy, became the new Director and Jack’s mentor. During his fellowship program in 1960 and 1961, he carried out, with Dr Sherman, studies concerned with antibody levels in pollen allergy and their responses to immunotherapy and continued these after he became an attending and Director of Research at the Roosevelt Hospital Cooke Institute of Allergy, publishing a series of articles through the next several years. In addition, he authored or coauthored articles on a variety of other subjects, including mouse anaphylaxis, penicillin allergy, nasal membrane pathology, and allergic rhinitis among others, totaling more than 50 articles in addition to many review articles in journals and textbooks. He was also greatly respected as a teacher and, despite his major interest in research, was known by his colleagues and fellows as stressing the practical aspects of clinical medicine, no doubt reflecting his prior experience in general practice. During these years, he became increasingly skeptical about the methods of evaluating the symptoms and signs of patients with hay fever. They were almost entirely subjective, with patients scoring their

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symptoms on a daily basis between visits to the clinic weekly or even less often. He observed that many of the symptoms were clearly scored by the patient on the way to the clinic, covering 1 or 2 weeks or more of daily evaluation, stating ‘‘of course, these reports were useless, as the patient’s recall of severity is usually of short duration.’’ The only objective symptom was nasal obstruction, and he noted that ‘‘examination of the nares was of dubious value, since so little of the airway can be seen, and one examination is a fleeting glimpse of an organ that can undergo gross changes in congestion in a matter of seconds. It seemed obvious that new tools and improvements in methods were necessary.’’ In his words, ‘‘for 2 years, first working with cardboard, glue and spit, and then wood, plastics, and finally electronics, I pursued the problem of designing and constructing an instrument for making these measurements. The final electronic instrument . could measure the pressure and flow rate through a respiratory cycle and provided a digital readout of the flow rate . . One of my major objectives was to be able to compare the nasal congestion in each nostril of a subject over different times.’’ He then designed an enclosed environment of pollen grains in a 28-L flask that was rotated to keep the pollen grains floating in the enclosed space, with a tube through which could be ejected pollen-laden air onto the nasal membrane. These ingenious inventions led to his discovering the ‘‘priming effect.’’ They had been so well conceived, that they were used in his studies through the rest of his career without ever needing any modification in design. The second major problem relating to experimental design—similar pollen exposure of patients in the same series—was subsequently addressed when a pharmaceutical company asked him to carry out a clinical study of an antihistamine-decongestant combination. He hired a large meeting room during the height of the pollen season at a motel in Indiana, which he converted to an office and laboratory for his instruments. Just outside the room was a spacious lawn, and he created a large sitting area with tents and furniture, where the subjects sat for 8 hours on 2 consecutive days from 9 AM to 5 PM and were evaluated hourly using both symptom cards and objective measurements of nasal congestion, with appropriate controls and pollen counts. With identical exposure for the subjects, this created as near a perfect study as possible, and this protocol was used in subsequent studies. By the time he left Roosevelt Hospital in 1973, he was devoting his research to the effect of topical and systemic medications in nasal allergy and infections for pharmaceutical companies. He spent 4 years as attending at St Vincent’s Hospital in New York City and then at Holy Name Hospital in New Jersey, while establishing a private laboratory, and for the last 16 years of his active career, he carried out approximately 200 such studies for various pharmaceutical companies.

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Although his earlier studies were usually with coworkers and he worked well as part of a team, Jack described himself as something of a loner, and for the latter part of his career, he preferred to carry out his studies on his own, helped by 1 or 2 assistants. He also gave the impression that he had little interest in organizational activities, but this is belied by a review of his record, which revealed that he was Chairman of the New York State Medical Society Section on Allergy in 1969 and President of the New York Allergy Society in 1968-1969 and served actively on several committees of the American Academy of Allergy, Asthma, and Immunotherapy from the time he became a member in 1963. A little-known contribution that he made was in 1968, coincidentally on the 25th anniversary of its founding, when he was chairman of the audio-visual committee and established the first luncheon seminars. He began with 30 seminars, with 1 or 2 moderators and 10 participants the first year. Its success required rapid expansion at subsequent meetings, adding breakfast seminars as well. In the 38 years since their inception, a total of 3995 seminars have been held, and they have become an integral part of the annual meetings. Jack never received nor wanted credit for this, but it had a major effect, with undiminished popularity among the Academy members and fellows. Jack retired in 1988 but never stopped being a carpenter and a gadgeteer. He has fully equipped carpenter shops in his New Jersey home and in his lakeside country house. He has built everything in his homes made of wood, including the country house itself, except for the roof, which his wife of 29 years (his former

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assistant) insisted be done by a professional roofer, more for Jack’s safety than for any inability on his part to do the job. His intellectual curiosity and his interest in medical advances have never waned, and his practical approach to clinical medicine and to life still reflects his early years as a general practitioner. The author thanks the staff of the Archives of the American Academy of Allergy, Asthma and Immunology and the Archives of the University of Wisconsin, Milwaukee for supplying the data on the luncheon seminars. Murray Dworetzky, MD Emeritus Clinical Professor of Medicine Weill Cornell Medical College New York, NY Disclosure of potential conflict of interest: M. Dworetzky has declared that he has no conflict of interest.

REFERENCES 1. Connell JT. Quantitative intranasal pollen challenges. I. Apparatus design and technique. J Allergy 1967;39:358-67. 2. Connell JT. Quantitative intranasal pollen challenge. II. Effective daily pollen challenge, environmental pollen exposure and placebo challenge on the nasal membrane. J Allergy 1968;41:123-39. 3. Connell JT. Quantitative intranasal pollen challenges. III. The priming effect in allergic rhinitis. J Allergy 1969;43:33-44.

Received for publication May 3, 2006; accepted for publication May 5, 2006. Available online June 30, 2006.

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