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• W4308489279 abstract "We are saddened to inform you of the passing of Dr Lawrence M. Lichtenstein at the age of 88 years. On behalf of his many colleagues, we wish to send along our deepest condolences to his family. In allergy and immunology circles, his life will continue to be celebrated through the many scientists whom he trained and the profound influence of his research on the field of allergic diseases. Larry was born in Washington, DC, and graduated from the Woodrow Wilson High School, a public school now called the Jackson-Reed High School. He then moved to Chicago, Illinois, where he attended the University of Chicago, as both an undergraduate and a medical student, matriculating with an MD degree in 1960. During his undergraduate years at the University of Chicago, Larry met and married Carolyn Eggert, who was also an undergraduate at the time. Together they moved to Baltimore, where Larry completed internal medicine training at the renowned Osler Medical Service at the Johns Hopkins University School of Medicine. Thus began his long and illustrious career at Johns Hopkins and his wonderful life together with Carolyn and their family. In the late 1950s, it had only recently been shown that tissue mast cells were a store of histamine, an autacoid that had been implicated as a cause of immediate hypersensitivity responses such as anaphylaxis. IgE antibody had yet to be discovered, and the basophil as an “allergic” cell was barely on the radar screen. As a physician-scientist, Dr Lichtenstein realized the importance of applying basic science to solve clinical problems. He first practiced this philosophy when he joined Dr Abraham Osler’s laboratory in the Johns Hopkins Department of Microbiology as a PhD graduate student in 1962. Working with Dr Osler, Larry performed seminal studies showing that histamine was present in blood in human basophils and provided solid evidence that allergens could induce the release of histamine in blood. This impactful study established an in vitro assay for assessing the biologic factors that controlled histamine release and allergic sensitivity. Abe Osler had been studying anaphylatoxins and complement, and he established a guinea pig ileum smooth muscle assay to detect histamine in solutions; but in Larry’s 1964 study with Abe, the released histamine was measured by an extraction method and a fluorometric technique that was eventually automated.1Lichtenstein L.M. Osler A.G. Studies on the mechanisms of hypersensitivity phenomena.J Exp Med. 1964; 120: 507-530Crossref PubMed Scopus (546) Google Scholar The flexibility of this in vitro approach led to a many-decades effort to characterize the biologic elements that controlled histamine release from leukocytes. It was not long before the cell involved was shown to be the circulating basophil, that IgE was the “reaginic” antibody responsible for mediating the response to allergens, and that IgE bound to the basophil through a specialized high-affinity receptor. The discovery of IgE antibody was made by the team of Drs Kimishige and Teruko Ishizaka, and Gunnar Johansson, and Larry’s laboratory often collaborated to establish and validate key details of this rapidly expanding field of immunology. Larry’s laboratory was also involved in the developing field of immunopharmacology, which became a central element to understanding the therapies that were to evolve from both academic- and industry-based research. Beginning around 1970, Larry partnered with Dr Phillip S. Norman to create what eventually became the Division of Allergy and Clinical Immunology within the Department of Medicine at the Johns Hopkins University School of Medicine. In a decades-long collaboration, Larry and Phil established many of the baseline observations necessary to understand the biology of immunotherapy and together they refined immunotherapy as a principal therapy for allergists and their patients that stands to this day. The Johns Hopkins division founded by Larry and Phil trained hundreds of PhD, MD, and MD/PhD postdoctoral fellows from around the world over the ensuing decades. In particular, the division developed a long-standing relationship with Professor Gianni Marone at the University of Naples Federico II in Naples, Italy, hosting and training many Italian scientists. Dr Lichtenstein was especially proud of receiving the Knight Grand Cross award (Cavaliere di Gran Croce Ordine al Merito della Repubblica Italiana) in 1998 in recognition of his outstanding service to the Italian Republic. The training program that Larry and Phil developed was organized around a highly collegial partnership of investigators focused on translational (bench and clinical) research. Most MD clinical fellows were trained in the laboratory and mingled with PhD fellows who were also in training. This highly integrated association of clinical and basic research was strongly fostered by them, leading to many seminal developments in the field of allergic disease research. After many years of being housed in the O’Neill Laboratories at Good Samaritan Hospital in northern Baltimore, Larry and Phil, with colleagues in the Division of Pulmonary Medicine and Critical Care, established the Johns Hopkins Asthma and Allergy Center at the Hopkins Bayview Campus in East Baltimore in 1989. The division that Larry and Phil created grew to include more than 25 full-time faculty and more than 50 staff and trainees. Building a faculty with both PhD and MD degrees within a clinical division facilitated novel collaborative research in a range of domains, including cellular biology, molecular biology, genetics, and clinical science. Many important clinical models emerged from this unique environment, and the highly collaborative approach to advancing the field that they innovated became a model for other institutions around the world. Indeed, Dr Lichtenstein promoted the use of human allergen provocation models (nose, lung, eye, skin, and sting) and pharmacology to examine disease pathophysiology, working with Drs Anne Kagey-Sobotka, David Golden, Robert Naclerio, Rebecca Bascom, David Proud, Peter Creticos, Susan MacDonald, Alkis Togias, and others, pioneering paradigm-changing approaches to the diagnosis, mechanisms, and treatment of allergic diseases. After nearly 40 years as the Division of Allergy and Clinical Immunology’s director and a leader and president of societies such as the American Association of Immunology, the American Academy of Allergy, Asthma and Immunology, and the Collegium Internationale Allergologicum, Larry retired in 2002 at the age of 67 and moved to Florida. His curriculum vitae boasts more than 700 publications, measured in today’s ruler with a Scopus H-index of 103. His most influential and highly cited work included publications in Science,2Lichtenstein L.M. Margolis S. Histamine release in vitro: inhibition by catecholamines and methylxanthines.Science. 1968; 161: 902-903Crossref PubMed Scopus (348) Google Scholar,3MacDonald S. Rafner T. Langdon J. Lichtenstein L. Molecular identification of an IgE-dependent histamine-releasing factor.Science. 1995; 269: 688-690Crossref PubMed Scopus (330) Google Scholar Nature,4Schleimer R.P. Lichtenstein L.M. Gillespie E. Inhibition of basophil histamine release by anti-inflammatory steroids.Nature. 1981; 292: 454-455Crossref PubMed Scopus (134) Google Scholar the Journal of Experimental Medicine,1Lichtenstein L.M. Osler A.G. Studies on the mechanisms of hypersensitivity phenomena.J Exp Med. 1964; 120: 507-530Crossref PubMed Scopus (546) Google Scholar,5Schroeder J. Lichtenstein L. MacDonald S. An IgE-dependent recombinant histamine-releasing factor induces IL-4 secretion from human basophils.J Exp Med. 1996; 183: 1265-1270Crossref PubMed Scopus (81) Google Scholar the New England Journal of Medicine,6Hunt A.F. Valentine M.D. Kagey-Sobotka A. Benton A. Amodio F. Lichtenstein L.M. A controlled trial of immunotherapy in insect hypersensitivity.N Engl J Med. 1978; 299: 157-161Crossref PubMed Scopus (592) Google Scholar, 7Creticos P.S. Peters S.P. Adkinson Jr., N.F. Naclerio R.M. Hayes E.C. Norman P.S. et al.Peptide leukotriene release after antigen challenge in patients sensitive to ragweed.N Engl J Med. 1984; 310: 1626-1630Crossref PubMed Scopus (308) Google Scholar, 8Bochner B.S. Lichtenstein L.M. Current concepts: anaphylaxis.N Engl J Med. 1991; 324: 1785-1790Crossref PubMed Scopus (363) Google Scholar the Journal of Allergy and Clinical Immunology,9Bascom R. Wachs M. Naclerio R.M. Pipkorn U. Galli S.J. Lichtenstein L.M. Basophil influx occurs after nasal antigen challenge: effects of topical corticosteroid pretreatment.J Allergy Clin Immunol. 1988; 81: 580-589Abstract Full Text PDF PubMed Scopus (184) Google Scholar and the Journal of Immunology.10MacGlashan Jr., D.W. Bochner B.S. Adelman D.C. Jardieu P.M. Togias A. McKenzie-White J. et al.Down-regulation of FceRI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody.J Immunol. 1997; 158: 1438-1445PubMed Google Scholar Larry’s numerous scientific accomplishments were expertly and succinctly summarized in a Legends in Allergy and Immunology tribute published in 2019.11Golden D.B.K. Legends in allergy and immunology: Lawrence M. Lichtenstein.Allergy. 2019; 74: 2545-2546Crossref Scopus (0) Google Scholar Larry’s legacy is well established. He was a consummate translational immunologist before such a thing was in vogue. Through his influence on his trainees and the faculty in the division, thousands of articles with countless advancements in the field, including numerous new drugs for treating allergic conditions, were produced. Those trained in the division are found throughout the world and include 18 division directors (among them, the 3 authors of this piece); 5 American Academy of Allergy, Asthma and Immunology presidents; and countless leaders in academia, industry, and the National Institutes of Health. Larry leaves behind a life well lived and a lasting impact on all those who had the good fortune to work with him." @default.
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• W4308489279 title "In lasting tribute: Lawrence M. Lichtenstein, May 31, 1934, to August 5, 2022" @default.
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