George Stamatoyannopoulos (1934–2018)
Authors: Cynthia E. Dunbar, David M. Bodine, Arthur W. Nienhuis
Journal: Molecular Therapy (2018)

George Stamatoyannopoulos, or George “Stam” to the many friends and colleagues unable to pronounce or spell his last name, was a larger-than-life physician-scientist who died on June 16, 2018 at the age of 84. George was born in Athens, Greece in 1934 and graduated at the top of his medical school class. He was recruited by Arno Moltulsky to the renowned medical genetics department at the University of Washington in 1964, along with Thalia Papayannopoulou, his wife and hematology collaborator. He was the chief of the Medical Genetics department from 1989–2005. George made many important research contributions to the fields of human genetics and hematology throughout his long and storied career, which continued in full swing despite serious medical challenges. His most recent accomplishment was the publication of a senior author paper in Nature just a few months ago, which combined his interest in ancient Greek civilization with his expertise in genetics to map the relationships between the Bronze Age peoples in the Mediterranean cradle of civilization.1Lazaridis I. Mittnik A. Patterson N. Mallick S. Rohland N. Pfrengle S. Furtwängler A. Peltzer A. Posth C. Vasilakis A. et al.Genetic origins of the Minoans and Mycenaeans.Nature. 2017; 548: 214-218Crossref PubMed Scopus (127) Google Scholar It is fitting that his first paper was also published in Nature, describing in 1962 the loss of HbA2 in some patients with β-thalassemia.2Fessas P. Stamatoyannopoulos G. Absence of haemoglobin A2 in an adult.Nature. 1962; 195: 1215-1216Crossref PubMed Scopus (14) Google Scholar George went on to make numerous important scientific and clinical contributions, publishing over 400 papers. Among the many highlights, he deeply characterized the genetic basis of the hemoglobinopathies, particularly the β-hemoglobinopathies prevalent in his Mediterranean homeland,3Stamatoyannopoulos G. The molecular basis of hemoglobin disease.Annu. Rev. Genet. 1972; 6: 47-70Crossref PubMed Scopus (25) Google Scholar linked heterozygous thalassemia mutations and resistance to malaria,4Stamatoyannopoulos G. Fessas P. Thalassaemia, Glucose-6-Phosphate Dehydrogenase Deficiency, Sickling, and Malarial Endemicity in Greece: A Study of Five Areas.BMJ. 1964; 1: 875-879Crossref PubMed Scopus (19) Google Scholar studied the population genetics of these disorders, championed genetic counseling, analyzed the molecular and cellular control of hemoglobin switching,5Enver T. Raich N. Ebens A.J. Papayannopoulou T. Costantini F. Stamatoyannopoulos G. Developmental regulation of human fetal-to-adult globin gene switching in transgenic mice.Nature. 1990; 344: 309-313Crossref PubMed Scopus (238) Google Scholar and discovered that persistently high levels of fetal hemoglobin in thalassemia patients could ameliorate anemia,6Gelinas R. Endlich B. Pfeiffer C. Yagi M. Stamatoyannopoulos G. G to A substitution in the distal CCAAT box of the A gamma-globin gene in Greek hereditary persistence of fetal haemoglobin.Nature. 1985; 313: 323-325Crossref PubMed Scopus (109) Google Scholar an observation that led directly to the concept of increasing fetal hemoglobin as therapy for hemoglobinopathies.7Veith R. Galanello R. Papayannopoulou T. Stamatoyannopoulos G. Stimulation of F-cell production in patients with sickle-cell anemia treated with cytarabine or hydroxyurea.N. Engl. J. Med. 1985; 313: 1571-1575Crossref PubMed Scopus (118) Google Scholar George was the driving force behind the development of the hemoglobin switching conferences, the first of which was held in 1978. These conferences have been held bi-annually ever since. The focus was on the molecular genetics of hemoglobin switching and translation of this knowledge to the development of new therapies. Both goals were realized in that there is now a detailed understanding of the molecular basis for hemoglobin switching. Furthermore, a therapeutic agent shown to increase HbF, hydroxyurea, is now in wide use for the treatment of sickle cell disease. 5-azacytadine, initially considered carcinogenic but now used routinely in myelodysplasia, was shown to potently induce fetal hemoglobin and is being used to treat thalassemia patients in which hydroxyurea is relatively ineffective. Over 25 years ago, George realized that genetic therapies would be able to cure genetic diseases and applied his laser-like focus and prodigious energies toward making gene therapy a reality. He became frustrated that existing professional societies did not provide an adequate “home” to bring together scientists and clinicians working in the nascent gene therapy field. In particular, George wanted to provide the networking opportunities, mentorship, and visibility needed to launch the careers of promising young investigators. In 1996, George convened a group of investigators working on gene therapy to incorporate the American Society of Gene Therapy (ASGT; later renamed the American Society of Gene and Cell Therapy). George’s goal for the nascent ASGT was nothing short of providing a catalyst to move gene therapy forward from multiple isolated technologies pursued by scientists and physicians working in different disciplines to a recognized field of science and medicine. In 1998, just 1.5 years after the incorporation of the society, George, as the founding President, hosted the first ASGT annual meeting in Seattle. At that time the society had precious few resources, but George believed that the society needed a signature meeting to establish itself. George was relentless in pursuing funding for that first meeting. He called every NIH Institute Director, promoting the society and its goals while asking for financial support. He similarly reached out to industry and to philanthropic organizations. As we all experienced, it was impossible to say no to George! Having secured the necessary financing, George went on to haggle the new Seattle Convention Center down to a bargain basement price and negotiated impossibly low hotel rates for meeting attendees. By any measure, the first meeting of ASGT in 1998 was a resounding success, immediately establishing the society as the voice of this new discipline. 761 abstracts were submitted and 1,630 investigators from around the world attended, 3 times more than any gene therapy meeting to date. In recognition of George’s role in founding ASGT and organizing its first annual meeting, the ASGT Board of Directors established the honorific George Stamatoyannopoulos Lecture as a permanent feature of all subsequent meetings of the Society. In an interview filmed last year and shown at the 20th Annual ASGCT meeting (https://www.youtube.com/watch?v=UWgAXTpAARQ), George eloquently described his conviction that the development of a strong scientific foundation to move gene therapy forward would be greatly facilitated by an annual meeting and his joy at seeing attendees streaming into the Seattle convention center on the opening day in 1998. George’s death is a major loss to gene therapy, genetics, and hematology as well as to his colleagues and mentees, including the three of us, who followed in his footsteps as ASGCT Presidents. His wise council and generosity of time and effort were critical to each of our efforts to grow ASGCT and the field of gene therapy. We are grateful that George lived long enough to witness the recent maturation of the field, with approved therapies for cancer, inherited blindness, and immunodeficiencies, and unequivocal clinical progress toward curative gene therapies for thalassemia and sickle cell anemia.8Dunbar C.E. High K.A. Joung J.K. Kohn D.B. Ozawa K. Sadelain M. Gene therapy comes of age.Science. 2018; 359: 359Crossref Scopus (678) Google Scholar ASGCT staff and members, colleagues at the University of Washington, collaborators in Greece and around the world, prior mentees, and patients with hemoglobinopathies will miss him but will undoubtedly continue to benefit from his scientific and organizational achievements for years to come. We send our condolences on behalf of ASGCT to his wife, Dr. Thalia Papayannopoulou, a physician-scientist and accomplished hematology investigator; his son, Dr. John Stamatoyannopoulos, a physician-scientist and a leader in molecular biology and epigenomics; his son Vassilios Stamatoyannopoulos; and his three grandchildren.