Portal de Periódicos da CAPES

In Memoriam

2023; Elsevier BV; Volume: 29; Issue: 12 Linguagem: Inglês

10.1016/j.eprac.2023.11.003

1934-2403

David C. Lieb, Henri K. Parson, Carolina Casellini, Elias S. Siraj,

Schizophrenia research and treatment

Dr. Aaron Israel Vinik, known to his friends as Arthur, was a giant in the world of endocrinology, known internationally for his research involving diabetes, diabetic neuropathy, and neuroendocrine tumors. He was extraordinary and a larger-than-life figure. There are those who follow a more traditional path created by others, and there are individuals who create their own path and make an extraordinary career along the way. Arthur clearly belongs to the latter. Arthur Vinik was born in 1937 in the Transvaal region of South Africa, an area known for its Mineral Revolution and subsequent economic boom in the late 19th and early 20th centuries. This economic boom led to a surge in immigration, with people arriving with aspirations of finding a better life. Arthur’s parents, Joseph and Fanny, who hailed from the Baltic country of Lithuania, joined the huge influx of Jewish immigrants to South Africa fleeing the persecution and religious intolerance under Tsarist Russia. Arthur’s parents opened a small store and raised their children in a hardworking and spirited community. When Arthur was young, he and his family moved to the town of Benoni, a town that developed out of the gold rush near the larger city of Johannesburg. He was always competitive and wanted to be the best in both academics and sports. He was known, as he would be throughout his life, as a great athlete. Regarding academics, Arthur recalls his parents’ feeling “that the most important single thing in life was to become well-educated”. He embraced this sentiment and would spend the rest of his life learning. Arthur entered medical school at the University of the Witwatersrand in Johannesburg in 1955. He was drawn to basic science and considered shifting his focus from clinical medicine to pure science, but at the urging of his father, he completed his medical school studies. During his medical school days Arthur was an avid soccer player and was known for participating in long games of bridge and for his skills at pinball. Perhaps the most important event in his medical school time was meeting Etta Fram. Etta, who grew up in the neighboring town of Springs, had graduated from Witwatersrand with majors in Latin, History of Art and Classical Life and Thought, and had completed a post-graduate year of study at Johannesburg Teachers’ Training College. Arthur and Etta were engaged in March of 1959 and married that December. Over the following 60-plus years of marriage Arthur and Etta not only successfully raised three sons, but also became collaborative partners on grants, research papers, educational programs, and international presentations. After medical school Arthur started his residency training in Johannesburg. He and Etta welcomed their first son, Howard, during his surgical residency at the Johannesburg General Hospital. Their second son Bryan was born shortly thereafter. While training at Chris Hani Baragwanath Hospital in Johannesburg, Arthur’s interests in endocrinology and metabolism were established, and he strengthened his prowess in the physical examination, medical history, and deep sense of empathy for patients. Arthur completed his chief residency at Baragwanath in 1965, and then became a fellow in the Department of Endocrinology, Metabolism and Diabetes at the University of Cape Town where he remained until 1968. During this time, he was able to participate in research and publications of many papers which included the use of the beta-adrenergic blocking agent propranolol in the treatment of patients with hyperthyroidism [1Vinik A.I. Pimstone B.L. Hoffenberg R. Sympathetic nervous system blocking in hyperthyroidism.J Clin Endocrinol Metab. 1968; 28: 725-727Crossref Scopus (41) Google Scholar]. While at Cape Town Arthur completed his PhD thesis involving fatty acid metabolism in persons with hyperthyroidism [2Vinik A.I. Pinstone B.L. Hoffenberg R. Studies on raised free fatty acids in hyperthyroidism.Metabolism. 1970; 19: 93-101Abstract Full Text PDF PubMed Scopus (10) Google Scholar]. During his fellowship Arthur and Etta had their third son, Steven, who Arthur delivered himself. Etta recalls that ‘the obstetrician had left the hospital for breakfast, and the nurses were busy elsewhere’. Following his fellowship training Arthur worked as a Senior Specialist Physician at King Edward VIII Hospital in Durban, on the eastern coast of South Africa. Arthur held a position as a Senior Lecturer in Chemical Pathology, and from 1969 to 1970 Arthur worked closely with Professor Septimus Matthys Joubert studying human growth hormone, it’s measurement via new immunoassays, its role in diabetes, and its role in clinical disease [3Vinik A.I. et al.Growth hormone response to insulin-induced hypoglycemia in diabetes secondary to chronic calcific pancreatitis.J Clin Endocrinol Metab. 1970; 31: 86-88Crossref Scopus (16) Google Scholar]. His work and interest in growth hormone soon took him to the United States. Upon graduating from fellowship, Arthur received an award from the South African Medical Council allowing him to complete a visiting fellowship with Drs. Melvin Grumbach (professor and chair of pediatrics) and Selna Kaplan (leader of the UCSF pediatric endocrine research laboratory) at the University of California in San Francisco. While at UCSF Arthur was involved in studies that better characterized human growth hormone and chorionic somatomammotropin [4Vinik A.I. Kaplan S.L. Grumbach M.M. Purification, characterization and comparison of immunological properties of monkey chorionic somatomammotropin with human and monkey growth hormone, human chorionic somatomammotropin and ovine prolactin.Endocrinology. 1973; 92: 1051-1064Crossref Scopus (8) Google Scholar]. This was not only a time for great learning, but a time for developing friendships over wonderful home-cooked meals. Dr. Kaplan was known for her cooking, and Etta recalls Selna feeding her and Arthur and the other endocrine fellows delicious meals in her home. In 1972 Arthur returned to Cape Town where he served as Associate Professor of Medicine at the University of Cape Town and Groote Schuur Hospital until 1978. During this incredibly productive time he published over 50 manuscripts in peer-reviewed journals and studied a broad array of endocrine topics. Much of Arthur’s work during this time focused on the diabetes seen in patients with pancreatitis, as well as the physiology of enteroendocrine hormones including gastrin and somatostatin [5Vinik A.I. The enterohormones. Current status and review.S Afr Med J. 1974; 48: 359-364Google Scholar, 6Kalk W.J. et al.Plasma gastrin responses to arginine in chronic pancreatitis.Diabetes. 1974; 23: 264-267Crossref Scopus (15) Google Scholar, 7Vinik A.I. Somatostatin and diabetes.S Afr Med J. 1977; 52: 97-98Google Scholar, 8Botha J.L. et al.Inhibition of exaggerated gastrointestinal glucagon responses in chronic pancreatitis by somatostatin.J Clin Endocrinol Metab. 1977; 45: 1265-1270Crossref Scopus (3) Google Scholar, 9Botha J.L. et al.The effect of somatostatin on epinephrine-induced free fatty acid release in normal man.S Afr Med J. 1977; 52: 995-997Google Scholar]. In 1978 Arthur and Etta would leave their home in South Africa yet again for Ann Arbor, Michigan, where Arthur would serve as Professor of Internal Medicine and Surgery at the University of Michigan until 1990. These were important years when Arthur would further develop prominence in the field of neuroendocrine physiology and neuroendocrine tumors. Arthur worked closely with surgical colleagues including Richard Fiddian-Green, his teacher from Baragwanath Hospital in Johannesburg, in caring for individuals with gastro-pancreatic neuroendocrine tumors and managed patients with associated carcinoid syndrome. He published pivotal work involving the use of somatostatin analogues in the treatment of these patients and drew much-needed attention from the clinical community to this rare tumor [10Tsai S.T. et al.Perioperative use of long-acting somatostatin analog (SMS 201-995) in patients with endocrine tumors of the gastroenteropancreatic axis.Surgery. 1986; 100: 788-795Google Scholar, 11Tsai S.T. Vinik A.I. Brunner J.F. Diabetic diarrhea and somatostatin.Ann Intern Med. 1986; 104: 894Crossref Scopus (32) Google Scholar, 12Vinik A.I. et al.Somatostatin analogue (SMS 201-995) in the management of gastroenteropancreatic tumors and diarrhea syndromes.Am J Med. 1986; 81: 23-40Abstract Full Text PDF PubMed Scopus (83) Google Scholar]. While Arthur thrived in wintery Michigan, one of his true loves was being on the water. He enjoyed sailing and waterskiing and was well-known for his abilities as a windsurfer. His longing for water would soon bring him to Norfolk, Virginia. In 1990 Arthur was recruited to develop and lead the research program at the Strelitz Diabetes Center at Eastern Virginia Medical School in Norfolk. The center had recently opened in 1987 and was an integral part of the medical school’s mission to improve health care in the region. Etta was hired to establish the Diabetes Center’s program for patient and professional education. Arthur and Etta thrived in Norfolk. Arthur further developed his focus on diabetic neuropathy and created one of the world’s preeminent research units for studying this common but often overlooked co-morbid disease. Dr Vinik and his team worked on identifying mechanisms of nerve damage and new therapeutic approaches oriented to prevent the onset of or ameliorate progression of the disease and promote nerve regeneration and repair. Much as he had done with neuroendocrine tumors, Arthur brought neuropathy to the forefront, ensuring that healthcare providers had proper diagnostic instruments and that patients had available therapies. Further, he offered patients with this terrible condition hope. Arthur’s work on diabetic neuropathy culminated in position statements and seminal publications on the diagnosis and treatment of diabetic neuropathy [13Vinik A.I. et al.American Association of Clinical Endocrinologists and American College of Endocrinology Position Statement on Testing for Autonomic and Somatic Nerve Dysfunction.Endocr Pract. 2017; 23: 1472-1478Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar, 14Tesfaye S. et al.Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments.Diabetes Care. 2010; 33: 2285-2293Crossref PubMed Scopus (1785) Google Scholar, 15Tesfaye S. et al.Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis, assessment and management.Diabetes Metab Res Rev. 2011; 27: 629-638Crossref PubMed Scopus (300) Google Scholar, 16Vinik A.I. CLINICAL PRACTICE. Diabetic Sensory and Motor Neuropathy.N Engl J Med. 2016; 374: 1455-1464Crossref PubMed Scopus (78) Google Scholar, 17Vinik A.I. The conductor of the autonomic orchestra.Front Endocrinol (Lausanne). 2012; 3: 71Crossref PubMed Scopus (43) Google Scholar]. Arthur and Etta became interested in health-related quality of life-based research, and together developed three tools for assessing quality of life in their patients. These included the Norfolk Quality of Life tools for those with diabetic neuropathy (QOL-DN), for neuroendocrine tumors (QOL-NET) and for fatigue (QOL-F) [18Vinik E.J. et al.The development and validation of the Norfolk QOL-DN, a new measure of patients' perception of the effects of diabetes and diabetic neuropathy.Diabetes Technol Ther. 2005; 7: 497-508Crossref PubMed Scopus (173) Google Scholar, 19Vinik E. et al.Development of the Norfolk quality of life tool for assessing patients with neuroendocrine tumors.Pancreas. 2009; 38: e87-e95Crossref PubMed Scopus (35) Google Scholar, 20Vinik E.J. et al.Development and Validation of the Norfolk Quality of Life Fatigue Tool (QOL-F): A New Measure of Perception of Fatigue.J Am Med Dir Assoc. 2020; 21: 1267-1272 e2Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar]. The questionnaires have been translated into close to 70 different languages and are used as endpoints in global clinical trials. While in Norfolk, Arthur also continued his pivotal work on islet neogenesis-associated protein, or INGAP. This work started the University of Michigan, when Arthur and his surgical colleague Dr. Lawrence Rosenberg discovered that obstruction of the pancreatic duct in hamsters led to islet neogenesis [21Fleming A. Rosenberg L. Prospects and challenges for islet regeneration as a treatment for diabetes: a review of islet neogenesis associated protein.J Diabetes Sci Technol. 2007; 1: 231-244Crossref Scopus (23) Google Scholar, 22Rosenberg L. et al.Induction of nesidioblastosis will reverse diabetes in Syrian golden hamster.Diabetes. 1988; 37: 334-341Crossref PubMed Scopus (67) Google Scholar]. Further work suggested that this neogenesis was under control of a growth factor and Arthur and his colleagues soon successfully sequenced and cloned the gene responsible for the expression of this factor [23Pittenger G.L. Vinik A.I. Rosenberg L. The partial isolation and characterization of ilotropin, a novel islet-specific growth factor.Adv Exp Med Biol. 1992; 321 (discussion 131-2): 123-130Crossref Scopus (35) Google Scholar]. They called the growth factor islet neogenesis-associated protein (INGAP), and further research involving INGAP has led to positive outcomes in studies involving persons with type 1 diabetes and in those with type 2 diabetes [24Dungan K.M. Buse J.B. Ratner R.E. Effects of therapy in type 1 and type 2 diabetes mellitus with a peptide derived from islet neogenesis associated protein (INGAP).Diabetes Metab Res Rev. 2009; 25: 558-565Crossref PubMed Scopus (47) Google Scholar]. Recent work has demonstrated that INGAP may have anti-inflammatory effects in the pancreatic islet that may represent new potential therapies for diabetes [25Nano E. Petropavlovskaia M. Rosenberg L. Islet neogenesis associated protein (INGAP) protects pancreatic beta cells from IL-1beta and IFNgamma-induced apoptosis.Cell Death Discov. 2021; 7: 56Crossref Scopus (9) Google Scholar]. Students from around the world came to Norfolk to train with Arthur and his growing team of clinicians and scientists. Of his many students, Arthur would say “It is…as if they are my children”. It is estimated that Arthur mentored over 100 physicians and researchers during his career, though this number is likely much higher. Arthur remembered his father telling him, “Everyday…learn my child”, and passed that dictum on to his three sons. Howard, Bryan, and Steven all graduated from the University of Michigan and would go on to careers in business, medicine, and finance. Arthur and Etta loved spending time with their children and their grandchildren. For his colleagues, Arthur was a wonderful collaborator. He would say “One can’t emphasize enough the importance of international bonds…in days gone by, if you were running a research lab, you had to wait to read the literature of what others had done, sometimes many years later…. with the advent of globalization and the Internet, we can know within a few hours what the whole world is doing”. Arthur was an incredibly productive scientist, publishing 11 books, 140 book chapters, and 600 original manuscripts. Throughout his career he held research grant funding from the National Institutes of Health, the American Diabetes Association, and others. He held numerous patents and was a member of numerous medical journal editorial boards. He was chosen to give prestigious invited lectureships across the world, from the Banting Lecture at the University of Toronto to the Minkowski Lecture in Kaunas, Lithuania, the homeland of his parents. He received the award for Virginia Outstanding Scientist in 2002, and the highest award at EVMS, the Dean’s Award for Outstanding Faculty in 1999. Arthur was an active member of numerous endocrine organizations, including the American Association of Clinical Endocrinology (AACE), which honored him with their Lifetime Distinction in Endocrinology Award, the Diabetic Neuropathy Study Group of the European Association for the Study of Diabetes (NEURODIAB) who recognized Arthur with their Lifetime Achievement Award, and the North American Neuroendocrine Tumor Society (NANETS) who presented him with their Lifetime Achievement Award in 2019. Arthur never had any intention of slowing down, clinically or in his research endeavors. He continued to sail and work in his garden, and Etta recalls Arthur being “one of the oldest kite-boarders on the water” at age 80. In Etta’s words, he was a “fitness fanatic”, and they loved dancing. Sadly, in 2018 Arthur suffered a significant stroke which forced his early retirement. At the time of his retirement in 2018 Arthur was named Professor Emeritus by EVMS, and an honorary professorship and lectureship have been named in his honor at the institution. Arthur died peacefully at his home surrounded by his family on June 15, 2023, approximately one month shy of what would have been his 86th birthday. At the time, he and Etta, the love of his life, had been married for 63 years. Arthur Vinik was an amazing clinician, educator, scientist, and scholar. Perhaps most important to Arthur, in addition to his quest for discovery, was his love for and love from his family. He treated his students and colleagues as family as well. Arthur’s spirit will continue to live on in all of those that he touched during his remarkable life.Arthur and his research team. Dr. Parson is 2nd from left in front row, and Dr. Casellini is 4th from left in back row.∗View Large Image Figure ViewerDownload Hi-res image Download (PPT)Arthur and the love of his life, Etta.∗View Large Image Figure ViewerDownload Hi-res image Download (PPT)A young Arthur (standing, left) with his father and siblings.∗View Large Image Figure ViewerDownload Hi-res image Download (PPT)Arthur, Etta, their boys and one of their four grandchildren.∗View Large Image Figure ViewerDownload Hi-res image Download (PPT)Arthur on the water.∗View Large Image Figure ViewerDownload Hi-res image Download (PPT)