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Robert Winslow's new book, Blood Substitutes, is useful in many ways. It brings together well-written summaries of the work of many of the most important investigators of the last 2 decades in this broad group of interrelated fields. Moreover, it also has some excellent chapters of scientific and medical background that provide context for the work. It also gives a historical snapshot of the thinking and attitudes of workers in the field.

As an introduction to the field, this book is outstanding. It gives a clear sense of the breadth of work on artificial oxygen carriers. This runs from perfluorocarbon and hemoglobin chemistry to clinical and battlefield resuscitation and on to the special roles of alternative oxygen carriers for radiosensitization and ischemic tissue perfusion. With more than 2000 papers in the blood substitutes literature, many are spread across uncommon and older journals and no other recent in-depth reviews, there really is no other place to start.

Perhaps, the hardest aspect for a beginner or even a long-time worker is the problem of all of the various points of view from which blood substitutes are regarded. Thus, chemists, process engineers, pharmacologists, toxicologists, physiologists, numerous specialties of physicians, capitalists, businesspersons, and government regulators each have special knowledge and points of view. The fine chapters on the limits of transfusion medicine by Harvey Klein, the regulatory environment by Toby Silverman and her colleagues from the US Food and Drug Administration, and oxygen transport by Robert Winslow are all simultaneously clear and comprehensive. More focused chapters by Kim Vandegriff on oxygen diffusion and Abdu Alayash on hemoglobin redox reactions are useful expositions of difficult concepts. In addition, the overviews on perflurorocarbon emulsions by Jean Reiss and Marie Pierre Craft and hemoglobin by Andrea Bellelli and Maurizio Brunori are almost perfect small reviews for understanding the background on the respective classes of products. The better chapters in this book represent some of the finest writing in the entire field. The general medical literature on this subject is nowhere near so clear or trustworthy.

Even as this book goes out of date, it will remain a remarkably useful historical source. It documents most of the major efforts in blood substitutes development up to 2005. It records the thoughts of many of a generation of senior technical leaders in this field near the end of their careers. It offers an extensive set of bibliographies.

The book is not as complete as it might appear at first glance. Specifically missing are reviews of the interactions of hemoglobin-based blood substitutes with bacteria and bacterial endotoxins and of hemoglobin-induced endothelial activation and thrombosis. The interactions of bacteria and hemoglobin, which caused increased lethality in animal models, are important because almost all wounded soldiers and many injured civilians are expected to have contaminated wounds, and resuscitation with hemoglobin may increase their morbidity. Hemoglobins have caused inflammatory changes in blood vessels and strokes and lung infarctions in animal models. Thrombotic episodes in clinical trials are therefore worrisome and deserve a fuller discussion. In addition, missing is any description of the Northfield Laboratories pyridoxylated, glutaraldehyde-polymerized human hemoglobin, the only product presently in a phase III trial.

More worrying, the book and specifically the editor let pass some of the more egregious unsubstantiated claims in the field. Two chapters on perfluorocarbon emulsion products claim that lack of money alone has prevented these synthetic oxygen carriers from coming to market, whereas dose-limiting toxicity and limited oxygen carrying capacity meant that under almost ideal conditions, they delivered less oxygen than half a unit of red cells. A chapter on trauma and combat casualty care claims that hemoglobin solutions have an important role in battlefield resuscitation. However, in any useful dose, the colligative activity of even the polymerized hemoglobins will potentiate coagulopathy, now recognized as the most important cause of preventable hospital deaths in trauma centers and combat support hospitals. In addition, in a chapter on the editor's own company's product, a polyethylene glycol conjugated hemoglobin, he downplays the very high osmotic activity of the material, which means that at any total hemoglobin concentration compatible with life, adding the material reduces the total oxygen carrying capacity.

The end result is that the book suggests a future for blood substitutes that is far rosier than rational analysis allows. But rational analysis has not been the sole driving force in this 2 billion dollar field. The book lacks chapters on folly, ethical lapses, and criminal behavior. These would have rounded out the story. Nonetheless, for information about the basic scientific background, there is no better place to go.