Legends in allergy: Philip S. Norman and Lawrence M. Lichtenstein-The Hopkins Experience

Through a research career that spanned 50 years, this prodigious collaboration provided the allergy community with the tools to design and perform clinical studies of immunotherapy based on sound scientific principles. Their studies of ragweed immunotherapy provide a framework for assessment of therapeutic efficacy based on measurable objective immunologic parameters: (1) a rise in serum IgG blocking antibodies. (2) a suppression of the typical seasonal rise in IgE antibodies followed by a steady decline in the level of specific IgE antibodies with a continued maintenance immunotherapy regimen, (3) an increase in blocking antibodies in nasal secretions, and (4) inhibition of allergen-induced histamine release from isolated human leukocytes (reduced basophil sensitivity and reactivity). Furthermore, their acumen in clinical trial design defined equally important clinical parameters that defined clinical success: (1) use of a well characterized allergen extract standardized based on major protein content (Amb a 1); (2) defining an optimal immunizing dose which minimized the systemic anaphylaxis engendered with maximally tolerated dose regimens; (3) use of immunotherapy for an adequate length of time through incorporation of a perennial maintenance immunotherapeutic regimen to induce lasting protection; and (4) defining the specificity of immunotherapy. In conclusion, their enormous body of work has advanced the discipline of allergy from what most would term an art into a defined science, based on sound scientific principles, and provided the practicing allergist-immunologist with a more precise practice of medicine.