RESUMEN
George Minot (1885-1950) was born in Boston, Massachusetts. He was great grandson of James Jackson, co-founder of Massachusetts General Hospital in 1821. Graduating from Harvard College he enrolled at Harvard Medical School and obtained his MD in 1912. As a house pupil (intern) at the hospital he became interested in diseases of the blood and began taking meticulous histories of dietary habits of patients with anemia.
Asunto(s)
Anemia Perniciosa/historia , Cristalografía/historia , Filatelia , Vitamina B 12/historia , Anemia Perniciosa/terapia , Historia del Siglo XX , Humanos , Premio Nobel , Estados Unidos , Vitamina B 12/farmacologíaRESUMEN
Increased blood cell regeneration in exsanguinated experimental animals treated either with liver or with aqueous liver extracts was reported by Whipple and by Jeney and Jobling, respectively. These findings stimulated Minot and Murphy to provide evidence for the efficacy of liver against anaemia in clinical studies. After oral administration of liver (45-50 g per day) for 45 patients with anaemia perniciosa improvement of the hematological status was demonstrated. Consequently, for proving the therapeutic value of liver therapy Whipple, Minot and Murphy received Nobel price in 1934. The isolation of the antianemic factor from the liver has been succeeded in 1948 and designated as vitamin B12. At the same time Lucy Wills applied yeast for the treatment of pregnant women with anemia related to undernourishment. The conclusions of this study inspired the discovery of folate. The detailed investigation of the mode of action of vitamin B12 and folate enriched our knowledge in the area of pathophysiology and extended the clinical application of these two drugs.
Asunto(s)
Anemia Perniciosa/historia , Ácido Fólico/historia , Vitamina B 12/historia , Anemia Perniciosa/tratamiento farmacológico , Anemia Perniciosa/metabolismo , Antineoplásicos/historia , Autoinmunidad , Ácido Fólico/uso terapéutico , Antagonistas del Ácido Fólico/historia , Deficiencia de Ácido Fólico/historia , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Vitamina B 12/uso terapéutico , Deficiencia de Vitamina B 12/historiaAsunto(s)
Anemia Perniciosa/historia , Jugo Gástrico/química , Vitamina B 12/historia , Anemia Perniciosa/dietoterapia , Anemia Perniciosa/etiología , Gastritis Atrófica/complicaciones , Gastritis Atrófica/historia , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Hígado/química , Vitamina B 12/química , Vitamina B 12/aislamiento & purificaciónRESUMEN
The discovery of vitamin B(12), the elucidation of its role in metabolism, and the effects and treatment of its deficiency occurred in distinct phases over more than 100 years, and it was the subject of two separate Nobel Prizes. The valuable contribution of clinical reports and studies of patients with pernicious anemia throughout the 19th century resulted in enough clinical definition to allow Minot and Murphy to put together the first hallmark study on treatment of the condition, leading them to a Nobel Prize. These researchers were not the first to suggest that an inadequacy of nutrients was the cause of pernicious anemia, but their particular input was a carefully designed intervention in well-characterized pernicious anemia patients, of a special diet containing large amounts of liver. They found consistent improvement in the clinical and blood status of all subjects, most of whom remained on remission indefinitely. After the successful intervention studies, the next advance was made by Castle who discovered that a gastric component, which he called intrinsic factor, was missing in pernicious anemia. Many years later, intrinsic factor was found to be a glycoprotein that formed a complex with vitamin B(12), promoting its absorption through ileal receptors. The vitamin was isolated by two groups simultaneously and was crystallized and characterized in the laboratory of Dorothy Hodgkin, contributing to her Nobel Prize in 1964. Subsequently, the various biochemical roles of vitamin B(12) were elucidated, including its important interaction with folate and their common link with megaloblastic anemia. Many of the early clinical studies recognized that vitamin B(12) deficiency also caused a severe neuropathy leading to paralysis and death, while post mortem analysis demonstrated spinal cord demyelination. Vitamin B(12) is still the subject of intense research and, in particular, its role in preventing these irreversible neurological lesions remains unclear.
Asunto(s)
Vitamina B 12/química , Vitamina B 12/historia , Vitamina B 12/farmacología , Anemia Perniciosa/complicaciones , Anemia Perniciosa/tratamiento farmacológico , Anemia Perniciosa/fisiopatología , Animales , Mucosa Gástrica/metabolismo , Historia del Siglo XX , Humanos , Factor Intrinseco/metabolismo , Premio Nobel , Vitamina B 12/aislamiento & purificación , Deficiencia de Vitamina B 12/complicaciones , Deficiencia de Vitamina B 12/tratamiento farmacológico , Deficiencia de Vitamina B 12/fisiopatologíaRESUMEN
George Hoyot Whipple (1878-1976) was awarded the Nobel Prize in Physiology and Medicine in 1934, along with Minot and Murphy for their studies in pernicious anemia. Whipple's name has been given to the bacterial disease which he describes in 1907 that we know today as Whipple's disease or intestinal lipodystrophy. He gave the name of thalasemia to the Mediterranean anemia of Cooley, and made diverse contributions to hematology and general pathology. He worked with William Welch in the Department of Pathology at Johns Hopkins Hospital and later became director of the University of Rochester. He died in 1976 at the age of 98.
Asunto(s)
Anemia Perniciosa/historia , Premio Nobel , Enfermedad de Whipple/historia , Anemia Perniciosa/terapia , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Insulina/historia , Estados Unidos , Vitamina B 12/historia , Enfermedad de Whipple/terapiaAsunto(s)
Anemia Perniciosa/historia , Deficiencia de Vitamina B 12/tratamiento farmacológico , Vitamina B 12/historia , Administración Oral , Anemia Perniciosa/tratamiento farmacológico , Historia del Siglo XX , Humanos , Inyecciones , Vitamina B 12/administración & dosificación , Deficiencia de Vitamina B 12/historiaRESUMEN
This review describes the early chronological events in the pursuit of a treatment for pernicious anaemia, and the subsequent discovery of vitamin B12 and the intrinsic factor. It details Castle's experiments which established the theory of extrinsic and intrinsic factors as hemopoietic principles, and describes the studies on purification of the anti-pernicious anaemia principle from liver tissue that terminated in the crystallization of vitamin B12 and identification of its coenzyme forms. Biochemical purification and characterization of the intrinsic factor secreted by the gastric parietal cells, and two other vitamin B12 proteins, R-binder (transcobalamin I, haptocorrin), and transcobalamin II, are discussed in detail. The biochemical reactions in micro-organisms and humans in which vitamin B12 is involved are then briefly reviewed, and finally and briefly the immunological basis of pernicious anaemia is discussed.