In the modern world, there is no shortage of people who know what is best for others. Self-appointed experts, consultants, and organizations try to convince states, corporations, and individuals that they would be better off if they only followed some specific rules about what to do. These rules are presented as being voluntary and advisory. They are standards, not mandatory directives, and they abound in modern life. Standards may concern what characteristics a telephone should have, how a company should report its financial transactions, how organizations should be managed, how states should treat their citizens, how children should be raised, and so forth. Even organizations as powerful as states and large corporations follow standards on how to organize, which policies to pursue, what kinds of services to provide, or how their products should be designed. Standards enable a higher degree of global order in the modern world than would exist without them. They facilitate coordination and cooperation even among people and organizations that are far apart. The book states that standardization is a much neglected area of social science — an area that has by no means received the attention it deserves in view of its importance to society. This book redresses the balance by providing an in-depth examination of a number of aspects of standardization, how it is formed, and what effects it has on the world in which we live.

This book discusses standards and standardization — the production of standards — as a form of regulation, and argues that standards generate a strong element of global order in the modern world. People and organizations all over the world follow the same standards. Standards facilitate coordination and cooperation on a global scale and create similarity and homogeneity even among people and organizations far apart from one another. Standards are instruments of control, and standardization is a form of regulation just as crucial as hierarchies and markets. This book looks at a number of aspects of standardization, how standards are created, and their consequences. Some examples of standardizers and standards as well as the adopters of the standards are given.

Standardization is closely related to expertise and is usually justified on the grounds that there are some people who know best. This chapter discusses the character of such expertise and its implications for democracy. It addresses the risk that expert groups may emerge claiming that they ‘know what is best’ but remaining responsible to no one. It examines what kind of expert knowledge is said to be embodied in standards, emphasizes that standards are expert knowledge stored in the form of rules, and considers the relationship between standardization and the role of experts in modern societies. Not all experts are standardizers; some are not involved in standardization at all. It is debatable whether all standardizers should be considered experts. Some of those who are called standardizers have often been criticized precisely for their lack of expert knowledge.

Azidothymidine (AZT) inhibits the replication of human immunodeficiency virus and it is the only drug so far licensed for treatment of acquired immunodeficiency syndrome (AIDS). A prerequisite for its antiviral activity is phosphorylation by cellular nucleoside kinases to the mono-, di-, and triphosphate levels. This study determined the capacity of isolated peripheral blood mononuclear cells (PBMC), resting or mitogen stimulated, from 36 different people of whom 5 were HIV+, to phosphorylate and accumulate intracellular AZT nucleotides. We found a large variation in the amount of products formed between PBMC treated at different times from the same individual as well as between the PBMC from different individuals. Resting PBMC showed the largest interindividual variation and their levels of AZT nucleotides were about 60-150-fold lower than in activated PBMC. The intracellular half lives of azidothymidine mono-, di-, and triphosphates, constituting, on the average, 96-99.2, 0.7-1.8, and 0.4-2.7% of total nucleotides at 0.08-1.6 microM AZT, respectively, were also determined. In mitogen-stimulated PBMC it was approximately 2.5 +/- 0.6 h for all the azidothymidine metabolites. The half-life for intracellular azidothymidine monophosphate in resting PBMC from two individuals was determined to 1.5 +/- 0.2 h. There appeared to be no significant difference in the AZT metabolism in PBMC from HIV-positive or-negative persons. A relative decrease in the intracellular formation of AZTDP and AZTTP from AZTMP was observed at concentrations of AZTMP above 1 microM. This fact may explain why lowering the doses of AZT still gives therapeutically efficient levels of the active metabolite AZTTP.

Azidothymidine (zidovudine, AZT) used for treatment of HIV infection blocks the viral reverse transcriptase after phosphorylation by cellular enzymes. The first step in this reaction is the formation of AZT monophosphate, primarily catalyzed by host cytoplasmatic thymidine kinase (TK1). The activity of TK1 was determined in extracts of PHA-stimulated peripheral blood mononuclear cells (PBMCs) from 20 healthy volunteers and 49 HIV-infected patients at different stages of disease. In both groups we found a large intra- and interindividual variation of TK activity. Because TK1 expression is cell cycle regulated the proportion of stimulated cells was determined in the samples and the median thymidine kinase activity calculated. It was 3.0 pmol/mg/min x % S phase in the HIV-seronegative group and 1.1 pmol/mg/min x % S phase in HIV-infected individuals. The difference in thymidine kinase activity is statistically significant (p = 0.0001). The concentration of TK1 protein in the same extracts was also determined by immunoblotting. A positive correlation (r = 0.74) was observed between TK activity and amount of TK1 protein. The reason for this downregulation of TK is still unknown but may be related to the anergy observed in lymphocytes from HIV-infected persons. The reduced capacity for intracellular phosphorylation of AZT in HIV-infected individuals may be an important factor in the emergence of clinical AZT resistance and should also be accounted for in testing AZT resistance in vitro with PBMCs from healthy blood donors.