The aspirin story - from willow to wonder drug.

The story of the discovery of aspirin stretches back more than 3500 years to when bark from the willow tree was used as a pain reliever and antipyretic. It involves an Oxfordshire clergyman, scientists at a German dye manufacturer, a Nobel Prize-winning discovery and a series of pivotal clinical trials. Aspirin is now the most commonly used drug in the world. Its role in preventing cardiovascular and cerebrovascular disease has been revolutionary and one of the biggest pharmaceutical success stories of the last century.

Blood at 70: its roots in the history of hematology and its birth.

This year we celebrate Blood's 70th year of publication. Created from the partnership of the book publisher Henry M. Stratton and the prominent hematologist Dr William Dameshek of Tufts School of Medicine, Blood has published many papers describing major advances in the science and clinical practice of hematology. Blood's founding antedated that of the American Society of Hematology (ASH) by more than 11 years and Stratton and Dameshek helped galvanize support for the creation of ASH. In this review, I place the birth of Blood in the context of the history of hematology before 1946, emphasizing the American experience from which it emerged, and focusing on research conducted during World War II. I also provide a few milestones along Blood's 70 years of publication, including: the growth in Blood's publications, the evolution of its appearance, the countries of submission of Blood papers, current subscriptions to Blood, and the evolution of topics reported in Blood's papers. The latter provides a snapshot of the evolution of hematology as a scientific and clinical discipline and the introduction of new technology to study blood and bone marrow. Detailed descriptions of the landmark discoveries reported in Blood will appear in later papers celebrating Blood's birthday authored by past Editors-in-Chief.

A journey in science: medical scientist in translation.

Real innovations in medicine and science are historic and singular; the stories behind each occurrence are precious. At Molecular Medicine we have established the Anthony Cerami Award in Translational Medicine to document and preserve these histories. The monographs recount the seminal events as told in the voice of the original investigators who provided the crucial early insight. These essays capture the essence of discovery, chronicling the birth of ideas that created new fields of research; and launched trajectories that persisted and ultimately influenced how disease is prevented, diagnosed and treated. In this volume, the Cerami Award Monograph is by Göran K Hansson, MD, PhD, Karolinska Institute. A visionary in the field of cardiovascular research, this is the story of Dr. Hansson's scientific journey.

Haematology in the Republic of Macedonia: present situation and brief history.

The development of clinical haematology in Macedonia has taken place over the past nine decades. The greatest expansion of its development took place in the second half of the 20th century. The oficial start of clinical haematology dates from 1956, when the Department of Haematology was founded within the framework of the Internal Medicine Clinic in Skopje. In the beginning, haematology represented a form of virtual sub-specialty, but its expansion was so progressive and rapid that it reached the highest peaks of Yugoslav haematology in those times. The period from 1968 to 1979 was a period of integral development of haematology and blood-transfusion science in Macedonia. Nowadays, the autonomous Public Health Institution, the University Hematology Clinic, is a unique healthcare, educational and scientific establishment in the Republic of Macedonia in its field of work. The diagnostics algorithm comprises cyto-morphologic and cyto-chemical analysis, through immunologic characterization with the assistance of a flow cytometer, to sophisticated molecular analysis for detecting genetic abnormalities. The therapeutic approach is based upon modern poly-haemotherapeutic protocols, application of monoclonal antibodies, immuno-modulatory agents, molecular target therapy and the use of alogeneic and autologous transplantation of fresh bone-marrow and frozen haemopoietic stem-cells. The current motto of the Haematology Clinic is: always help those who seek help, provide precise and early diagnostics, and apply all up-to-date therapeutic strategies, scientific research, continual education and day-to-day implementation of the latest achievements in the field of haematology in daily practice.

The effect of Rh-negative disease on perinatal mortality: some evidence from the Skellefteå region, Sweden, 1860-1900.

The Rh-negative gene is a well-known cause of perinatal mortality. In this article, we analyze the possible role of Rh disease in perinatal mortality and stillbirths in a particular historical setting: the Skellefteå region in northern Sweden between 1860 and 1900. The data used for the study cover 23,067 children born to 4,943 women. The exact impact is not possible to establish using historical data, but the typical pattern of the disease allows us to make estimations. The expected levels based on knowledge of blood group distribution, the risk of sensitization from Rh incompatability, and the risk of perinatal mortality in births by sensitized mothers are compared with the observed levels. The results show that Rh disease was important for perinatal mortality and clustering of deaths within families.

The contribution of randomized trials to the cure of haematological disorders from Bradford Hill onwards.

It is now 75 years since the publication of Sir Austin Bradford Hill's classic textbook on Medical Statistics, and half a century since the formation of the Medical Research Council Working Party on Leukaemia. In the intervening period, trials in haematological malignancies have been at the forefront of cancer research, both in the proportion of patients recruited, and in the adoption of novel trial designs. In this paper, the principles propounded by Hill for reliable evaluation of new treatments are considered and placed in the context of the development and evaluation of novel treatments in the 21st century. Many of the original principles espoused are still highly relevant today, while the emerging heterogeneity of the conditions, both in aetiology and outcome provide their own newer challenges, which are discussed here.

Blood clotting and coagulation factors: the work of Yale Nemerson. 1980, 1982.

After developing a blood disorder, Yale Nemerson became interested in hematology. This led to his lifelong study of thrombogenic tissue factor and to his contributions to developing the modern theory of blood coagulation. The two Classic papers reprinted here detail some of Nemerson's studies on coagulation factors IX and VII.

Milestones in umbilical cord blood transplantation.

Much has been learned about umbilical cord blood (UCB) since the first human cord blood transplant was performed back in 1988. Cord blood banks have been established worldwide for the collection, cryopreservation and distribution of UCB for allogeneic haematopoietic stem cell transplantation. UCB has now become one of the most commonly used sources of haematopoietic stem cells for allogeneic transplantation. Today, a global network of cord blood banks and transplant centres has been established with a large common inventory, allowing for more than 20000 transplants worldwide in children and adults with severe haematological diseases. Several studies have been published on UCB transplant, assessing risk factors such as cell dose and human leucocyte antigen mismatch. New strategies are ongoing to facilitate engraftment and reduce transplant-related mortality and include the use of reduced-intensity conditioning regimen, intra-bone injection of cord blood cells, double cord blood transplants or ex vivo expansion of cord blood cells. The absence of ethical concern and the unlimited supply of cells explain the increasing interest of using UCB for developing regenerative medicine.

Ernest Beutler: his life and contribution to medical science.

Ernest Beutler was one of the preeminent haematologists of the last half of the 20th and the early 21st century. In a career that spanned six decades, his research interests included such diverse areas as red cell metabolism, blood preservation, glycolipid storage diseases, leukaemias and iron metabolism. Indeed, he was quite different from most of his contemporaries in that his knowledge encompassed not only haematology and not only the medical sciences, but the biological sciences as a whole. He was among the first to describe X chromosome inactivation, and he established the critical link between glucose-6-phosphate dehydrogenase deficiency and drug-induced haemolysis. He was a skilled and innovative clinician, and an early advocate of bone marrow transplantation for the treatment of acute leukaemia. He was a prolific author, with over 800 publications; a long time member of the Editorial Board of Blood; founder of the journal Blood Cells Molecules and Diseases; and an editor of Williams Haematology from the time of its inception. He bequeathed $1 million to the American Society of Haematology to recognise and reward outstanding basic research and its clinical application: a pursuit to which he had committed his life. Indeed, he became an extraordinary exemplar of the bench-to-bedside ethos, which holds that even today, an MD researcher, working with limited means and independent of pharmaceutical companies, can have a great impact on the practice of medicine.

Zebrafish in hematology: sushi or science?

After a decade of the "modern era" of zebrafish hematology research, what have been their major contributions to hematology and what challenges does the model face? This review argues that, in hematology, zebrafish have demonstrated their suitability, are proving their utility, have supplied timely and novel discoveries, and are poised for further significant contributions. It presents an overview of the anatomy, physiology, and genetics of zebrafish hematopoiesis underpinning their use in hematology research. Whereas reverse genetic techniques enable functional studies of particular genes of interest, forward genetics remains zebrafish's particular strength. Mutants with diverse and interesting hematopoietic defects are emerging from multiple genetic screens. Some mutants model hereditary blood diseases, occasionally leading to disease genes first; others provide insights into developmental hematology. Models of malignant hematologic disorders provide tools for drug-target and pharmaceutics discovery. Numerous transgenic zebrafish with fluorescently marked blood cells enable live-cell imaging of inflammatory responses and host-pathogen interactions previously inaccessible to direct observation in vivo, revealing unexpected aspects of leukocyte behavior. Zebrafish disease models almost uniquely provide a basis for efficient whole animal chemical library screens for new therapeutics. Despite some limitations and challenges, their successes and discovery potential mean that zebrafish are here to stay in hematology research.

Glucose-6-phosphate dehydrogenase deficiency: a historical perspective.

Glucose-6-phosphate dehydrogenase deficiency serves as a prototype of the many human enzyme deficiencies that are now known. Since its discovery more than 50 years ago, the high prevalence of the defect and the easy accessibility of the cells that manifest it have made it a favorite tool of biochemists, epidemiologists, geneticists, and molecular biologists as well as clinicians. In this brief historical review, we trace the discovery of this defect, its clinical manifestations, detection, population genetics, and molecular biology.