ABSTRACT

Biotechnology has entered our culture as something that solves many problems in health and agriculture. There is also a belief that biotechnology is something that appeared in the twentieth century. Biotechnology is de€ned as the use of biological methods and entities such as enzymes and/or organisms to produce a product. Given this broad de€nition, biotechnology can range from baking bread, making yogurt, and brewing beer to the use of recombinant DNA technology to produce therapeutic proteins. So, when a “talking head” is ponti€cating about the biotechnology industry, it may be about beer, bread, or Betaseron®. A similar confusion exists in the use of the term biopharmaceutical.1 In the context of the current work, biotechnology is used to describe the use of human blood plasma as a starting material for the manufacture of therapeutic products. Where relevant, the production of recombinant products based on plasma proteins is discussed as is the use of a protein as a diagnostic analyte. The use of blood plasma as a source of biomarkers is not discussed in detail, and the reader is referred to other sources.2-4

In my previous books, I had written the €rst chapter €rst, which seemed to make some sense. As I have matured (a colleague at Iowa suggested that I pass on candles for the birthday cake this year as a contribution to stemming global warming), I have noticed that the €rst chapters appear to have been (a) written by someone else (guilt falls on a cat, Callee, who shares my domicile) or (b) written by the author in one of his earlier states of mind. This time, the €rst is last; however, the last is not €rst. I want to emphasize that, despite having spent most of my professional career working on blood coagulation proteins (there was a brief time of sanity in New York), I really found out how much I did not know about plasma proteins until I started writing this book. There were a number of epiphanies but none for me was larger than €nding that substantial quantities of plasma proteins are in the extravascular space; in some instances such as with serpins, there is signi€- cant function in the extravascular space. An examination of physiology texts5-8 will provide a number of functions for blood, including oxygen transport, nutrient and hormone transport, and temperature regulation. Other functions such as hemostasis are intended for the maintenance of the integrity of the vascular system. Schaller and colleagues9 recently published an excellent book on the molecular and structural biology of the plasma proteins. These researchers developed a list of eight classes of plasma proteins ranging from proteins secreted by hard tissues (classical plasma proteins) to foreign proteins contributed by pathogenic and nonpathogenic organisms. They were then discussed by function, starting with blood coagulation and ending with transport and storage. I was encouraged to see that these workers also had a category for additional proteins, as the current work includes Chapter 9

(Miscellaneous Plasma Proteins). With reference to Schaller and colleagues,9 the current work is directed toward the use of “classical plasma proteins” and includes immunoglobulins, which would fall into a bit of a gray zone with their classi€cation system. I have no quarrel with their classi€cation and would note that several of their categories such as tissue leakage proteins, aberrant secretions, and receptor ligands are also diagnostic target/biomarkers. It is useful to appreciate that the extensive use of blood for the diagnosis of systemic disorders is a somewhat recent practice and the development/application of biomarkers is an even more recent practice2-4 in the sense that blood has been used in religious rites and furniture manufacture for centuries.