The rise and fall of heterologous transfusion.

Now a routine lifesaving treatment, blood transfusion between humans became a safe procedure only after many early therapeutic disasters. Performed between different species, heterologous transfusions actually succeeded homologous transfusions, those performed between members of the same species. In the early history of transfusion, both homologous and heterologous transfusions were performed in many clinical settings. Early clinicians were unable to distinguish between deaths caused by baseline illness and those resulting from transfusions. This report examines both early experiments with homologous transfusion between animals and later efforts investigating and finally abandoning heterologous transfusion. Topics explored include: 1) contributions and lessons learned from key individuals, 2) how these researchers suggested, performed, advocated, or challenged the practice of heterologous transfusion, and 3) why heterologous transfusions were even considered as a mode of therapy.

Out with the old, in with the new: Virtual versus physical crossmatching in the modern era.

The virtual crossmatch (VXM) is gaining acceptance as an alternative approach to assess donor:recipient compatibility prior to transplantation. In contrast to a physical crossmatch, the virtual crossmatch does not require viable donor cells but rather relies on complete HLA typing of the donor and current antibody assessment of the recipient. Thus, the VXM can be performed in minutes which allows for faster transplant decisions thereby increasing the likelihood that organs can be shipped across significant distances yet safely transplanted. Here, we present a brief review of the past 50 years of histocompatibility testing; from the original complement-dependent cytotoxicity crossmatch in 1969 to the new era of molecular HLA typing, solid-phase antibody testing and virtual crossmatching. These advancements have shaped a paradigm shift in our approach to transplantation. That is, foregoing a prospective physical crossmatch in favor of a VXM. In this review, we undertake an in-depth analysis of the pros- and cons- of physical and virtual crossmatching.Finally, we provide objective data on the selected use of the VXM which demonstrate the value of a VXM in lieu of the traditional physical crossmatch for safe and efficient organ transplantation.

[The international network and Italian modernization. Ruggero Ceppellini, genetics, and HLA]. / NETWORK INTERNAZIONALI E MODERNIZZAZIONE ITALIANA. RUGGERO CEPPELLINI, LA GENETICA E L'HLA.

The paper reconstructs the scientific career of Ruggero Ceppellini, focusing especially on his role in the discovery of the genetic system underlying the Human Leucocyte Antigen. From his earliest investigations in blood group genetics, Ceppellini quickly became an internationally acknowledged authority in the field of immunogenetics--the study of genetics by means of immunological tools--and participated to the endeavor that ultimately yelded a new meaning for the word: thanks to the pioneering research in the HLA field, immunogenetics became the study of the genetic control of immune system. The paper will also place Ceppellini's scientific work against the backdrop of the modernization of Italian genetics after WWII, resulting from the efforts of a handful of scientists to connect to international networks and adopting new methodologies in life sciences.

The original blood group pioneers: the Hirszfelds.

Ludwik Hirszfeld, together with his wife Hanka, was the first to study the blood groups in large numbers of subjects (soldiers) during World War I at the Macedonian front. They found significant differences in the distribution of the ABO blood groups, that is, type A was more common in soldiers from North Central Europe, whereas type B was more common in those from Eastern Europe. Their data were later (in the 1920s and 1930s) misused by German nationalists to support the concept of Aryan supremacy. The Hirszfelds also discovered Salmonella paratyphi C, now known as Salmonella hirzfeldi. Their landmark studies drew others to this new field of seroanthropology, most notably Arthur Mourant, as well as Robin Race and Ruth Sanger, who wrote "Blood Groups in Man" detailing the antigenic differences among various peoples.

Participating in the evolution of transfusion medicine from a dispensary into a discipline.

Collecting, processing and dispensing blood for hemotherapy has evolved into transfusion medicine (TM), a newly recognized discipline. Joining my efforts to those of collaborators all over the world during this period of transformation, my scientific career spanned from the investigation of the immunogenetics of Bombay (OhOh) blood to the establishment of the academic TM program at the University of California, San Francisco (UCSF) (San Francisco, Calif). The twin discoveries of class-specific antibodies against immunoglobulin A (IgA) causing anaphylactic transfusion reactions and of anti-IgA of limited specificity defining A2m(1) as the first genetic marker of IgA led to the award of the Julliard Prize. My precocious appointment as the head of the Bombay Municipal Blood Center in India launched my academic career in 1969 as the Chief of the blood bank at UCSF Medical Center. Viral hepatitis, then the principal risk of transfusion, engaged me in the molecular analyses of purified hepatitis B virus (HBV) and its surface antigen. Consequently the first HBV vaccine, derived from infected plasma (superseded by cloned HBV envelope protein) and hepatitis B immune globulin were developed for clinical trials that led to Food and Drug Administration-licensed biologic products for prophylaxis and therapy. The advent of HIV/AIDS in the early 1980s raised renewed concern about transfusion safety and led me to push for hepatitis B core antibodies blood screening for improved transfusion safety. The triennial International Symposia on Viral Hepatitis and Liver Disease, which I started in 1972, continue to be the foremost forum for the contemporary assessment of hepatitis prevention and treatment. Besides viral hepatitis, I undertook multiplexed flow cytometric analyses for markers of infection by blood-borne viruses and their polymerase chain reaction-amplified gene products, kinetics of HIV replication in peripheral blood lymphocytes, leukocyte depletion for safer transfusion, and removal/inactivation of blood-borne viruses. The TM training and research programs I initiated at UCSF in the 1980s with National Institutes of Health support enabled me to recruit new faculty members who continue to foster the worldwide advancement of transfusion safety.

The use of blood-type tattoos during the Cold War.

BACKGROUND: We have seen a number of individuals who received blood-type tattoos on the left side of the chest as schoolchildren in northwest Indiana during the 1950s. OBJECTIVE: To investigate the history of blood-type tattooing. METHODS: Historical research was conducted using newspaper and journal articles found in medical libraries, online archives, American Medical Association archives, Chicago Historical Society records, local medical society documents, in addition to personal interviews. RESULTS: Blood-type tattoos were used during the Cold War to enable rapid transfusions as part of a "walking blood bank" in case of atomic attack. Nationwide blood-typing programs occurred to inform individuals of their own blood types and to provide local communities with lists of possible donors. The blood-type tattooing program was part of this effort, but community-wide tattooing occurred only in two parts of the United States: Lake County, Indiana, and Cache and Rich counties, Utah. In these communities, during 1951 and 1952, schoolchildren were tattooed to facilitate emergency transfusions. LIMITATIONS: Events occurred more than 50 years ago, so we relied on original documents and interviews from individuals involved in the program who are still alive. CONCLUSIONS: The use of blood-type tattoos was short lived, lasting less than a year, and ultimately failed because physicians did not trust tattoos for medical information.

[Physical anthropology studies at Keijo Imperial University Medical School].

Medical research during the Japanese Colonial Period became systematic and active after the Keijo Imperial University Medical School was established in 1926. Various kinds of research were conducted there including pharmacological, physiological, pathological and parasitological research. The Keijo Imperial University was give a mission to study about Korea. Urgent topics for medical research included control of infectious diseases, hygiene and environmental health that might have affected colonizing bodies of the Japanese as well as the colonized. The bodies of Koreans had been studied by Japanese even before the establishment of the University. The Keijo Imperial University research team, however, organized several field studies for physical anthropology and blood typing research at the national scale to get representative sampling of the people from its north to its south of the Korean peninsula. In the filed, they relied upon the local police and administrative power to gather reluctant women and men to measure them in a great detail. The physical anthropology and blood typing research by the Japanese researchers was related to their eagerness to place Korean people in the geography of the races in the world. Using racial index R.I.(= (A%+AB%)/(B%+AB%)), the Japanese researchers put Koreans as a race between the Mongolian and the Japanese. The preoccupation with constitution and race also pervasively affected the medical practice: race (Japanese, Korean, or Japanese living in Korea) must be written in every kind of medical chart as a default. After the breakout of Chinese-Japanese War in 1937, the Keijo Imperial University researchers extended its physical anthropology field study to Manchuria and China to get data on physics of the people in 1940. The Japanese government and research foundations financially well supported the Keijo Imperial University researchers and the field studies for physical anthropology in Korea, Manchuria and China. The physical anthropology research was actively conducted hand in hand with imperialistic expansion, and driven by zeal for measuring the body.

Physical Anthropology Studies at Keijo Imperial University Medical School / 의사학

Medical research during the Japanese Colonial Period became systematic and active after the Keijo Imperial University Medical School was established in 1926. Various kinds of research were conducted there including pharmacological, physiological, pathological and parasitological research. The Keijo Imperial University was give a mission to study about Korea. Urgent topics for medical research included control of infectious diseases, hygiene and environmental health that might have affected colonizing bodies of the Japanese as well as the colonized. The bodies of Koreans had been studied by Japanese even before the establishment of the University. The Keijo Imperial University research team, however, organized several field studies for physical anthropology and blood typing research at the national scale to get representative sampling of the people from its north to its south of the Korean peninsula. In the filed, they relied upon the local police and administrative power to gather reluctant women and men to measure them in a great detail. The physical anthropology and blood typing research by the Japanese researchers was related to their eagerness to place Korean people in the geography of the races in the world. Using racial index R.I.(= A%+AB%/B%+AB%), the Japanese researchers put Koreans as a race between the Mongolian and the Japanese. The preoccupation with constitution and race also pervasively affected the medical practice: race (Japanese, Korean, or Japanese living in Korea) must be written in every kind of medical chart as a default. After the breakout of Chinese-Japanese War in 1937, the Keijo Imperial University researchers extended its physical anthropology field study to Manchuria and China to get data on physics of the people in 1940. The Japanese government and research foundations financially well supported the Keijo Imperial University researchers and the field studies for physical anthropology in Korea, Manchuria and China. The physical anthropology research was actively conducted hand in hand with imperialistic expansion, and driven by zeal for measuring the body.

Rare blood donors: a personal approach.

The National Blood Group Reference Laboratory (NBGRL) in Israel was established in Jerusalem in 1971 and transferred to Magen David Adom (MDA), National Blood Services in 1995. This laboratory was the inspiration of the first author of this article for over 30 years. The realization of this vision was made possible by the cooperation of colleagues and laboratory workers in blood transfusion services throughout the country. The aim of the service was to provide diagnostic help in resolving immunohematologic problems found in the blood banks and clinics in Israel. In the beginning, only a part-time technician performed the work and testing was done using very limited reagents. The service was expanded by personal visits to all of the 22 blood banks in Israel to explain the aim of this new service and to educate them about the importance of resolving each and every case. One major issue was the cost involved in referring problems but it was decided at the outset that these would be covered by the government to ensure that a workup would be performed for all referred cases. The expansion of the service could not have been achieved without the help of the SCARF program. This voluntary service enabled us to identify the first rare donors in Israel, resolve complex cases, and find compatible blood for our patients. To illustrate the importance of the NBGRL in Israel and the rapid resolution of cases referred, several individual stories are described. The purpose of this review is to show the importance of the NBGRL in identifying rare blood groups and in providing and coordinating services and the importance of keeping in close contact with the rare donors to encourage and promote their donations, which may save lives.

Platelet transfusion therapy: from 1973 to 2005.

Platelet transfusions are indispensable for supportive care of patients with hematological diseases. We describe the developments in platelet products for transfusion since the 1970s, when, in particular, support for patients with allo-antibodies against human leukocyte antigens was a laborious exercise with a high failure rate. Currently, due to many stepwise innovations, platelet transfusions are of low immunogenicity and sufficiently available, they have a shelf life up to 7 days, and even matched platelets can often be routinely delivered, provided that there is good communication between all partners in the chain. Future improvements can be expected from uniform type and screen approaches for immunized patients and cross-matching by computer. For efficient use of health care resources, blood banks and stem cell donor banks could share their typed donor files.

Hints to blood groupers, 1950.

Sixty years ago, the premier blood grouping laboratory was that of Robert Race in London. Agglutination tests and blood grouping had provided breakthroughs in immunology, genetics, and the solution of clinical problems. The significance of immunohematology was recognized by the clinical hematology community as a potent force in the expanding field of disorders of the blood and blood-forming organs. The instructions by Race to his London workers entitled Hints to Blood Groupers provide a picture of the immunohematology laboratory even before automation and differed slightly from the American techniques that derived from Landsteiner. Before agglutination is replaced in the near future by the emergence of molecular methods, the detailed method of a superb laboratory is recorded.

[The proof of paternity. An andrological-forensic challenge in historical perspective]. / Der Vaterschaftsnachweis. Eine andrologisch-rechtsmedizinische Herausforderung im Spiegel vergangener Zeiten.

For centuries, difficulties have occurred in determining unresolved paternities. In addition to the modern standard methods, such as the examination of DNA or serological proof, expert opinion on fertility once played an important role. The andrological difference between incapability to fertilise and the inability to participate in sexual intercourse was also distinguished historically. Of special significance was the discovery of spermatozoa by the medical student Johan Ham in 1677 and their further investigation by Antoni van Leeuwenhoek.Recently, modern DNA methods have also been applied for historical investigations. Illustrious examples are the DNA analysis in the case of Kaspar Hauser of Ansbach and the dispute about Thomas Jefferson, President of the U.S., fathering a child by one of his slaves. In this discourse, a medicinal-forensic review of the development of expert opinion, illustrated with historical case studies, is given.