© 2002 American Thoracic Society
Rebuttal from Dr. GelfandNational Jewish M edical and Research Center Denver, Colorado Pretentious, misdirected, problematic data, lack of awareness of asthma-like pathophysiology, and misguided efforts of hundreds of committed researchers characterize the "wishful thinking" that Dr. Persson has labeled the large amount of work performed in murine models. He advocates for more in vivo models of asthma, although these models are as readily available as patients are, but these studies are necessarily restricted. Asthma is not as simple as plasma exudation or epithelial injury and shedding, which have not necessarily been well-correlated with altered airway function. Asthma is a long-standing chronic syndrome, reflected in the heterogeneity from patient to patient and even the same patient at different time points. Examination of a patient with asthma is not only limited but simply a snapshot in time, potentially resulting in overinterpretation and misleading information. If there was "undisputable knowledge about the human disease," we would not need models. In the absence of such critical information, models and testable hypotheses are developed. Although the end results in mice and humans may show obvious or subtle differences, it is the means to get there that are critical—here is where studies in the mouse have provided not only essential information but have guided investigations of human asthma. To be specific, evidence, albeit limited, for mouse eosinophil degranulation has been presented (1, 2) but not accepted by Persson and colleagues (3). In humans, evidence for degranulation in vivo is also limited. Differences described between human and mouse eosinophils have been defined in in vitro systems primarily. Why then does Persson demand, for example, that valid extrapolation to asthma patients requires eosinophil degranulation in the mouse? This argument presupposes that all eosinophil effector factors are dependent on degranulation. The value of a small animal model, independent even of the multiple genetic and immunologic tools and markers that mice provide, lies in its use in exploring biologic plausibility for asthma pathogenesis and therapeutic manipulations. To conclude that progress in human asthma research has been slowed by the work in mice is only an admission of comfort with old problems rather than attempting to find new solutions. REFERENCES
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