Molecular biology and Pauling's immunochemistry: a neglected dimension

This paper argues that there is a substantial overlap between the history of immunology and the history of molecular biology, an overlap manifested in the researches on antibodies during the 1930s and 1940s. This common ground is a product of intellectual developments, as well as institutional trends. Viewed from an intellectual vantage point of the 1930s and 1940s, molecular biology was essentially the study of the biological specificities of the so-called 'giant protein molecules'. Within the conceptual framework of early molecular biology, which was rooted in the protein view of life, the concepts of protein template, autocatalysis, and heterocatalysis were central in explaining the protein syntheses of genes, viruses, enzymes, hormones, and antibodies. Immunochemistry and serological genetics were at the heart of that research agenda. This paper also shows that the immunochemistry program of Linus Pauling, which focused on molecular mechanisms of antibody structure and function, and the projects in serological genetics at Caltech's biology division were supported by the Rockefeller Foundation under the aegis of its molecular biology program. Based on the close examination of intellectual and institutional factors, the histories of molecular biology and immunology in the pre-DNA era are seen as closely linked.     

Male fertility: a case of enzyme identity

The plant hormone jasmonate has been implicated in male fertility in Arabidopsis. Recent studies have identified the enzyme required for a critical step of jasmonate synthesis in anthers and shown that this enzyme really is required for male fertility.     

Microbial antagonism: a neglected avenue of natural products research

Competition amongst microbes for space and nutrients in the marine environment is a powerful selective force which has led to the evolution of a variety of effective strategies for colonising and growing on surfaces. We are particularly interested in the chemical ecology of marine epibiotic bacteria which live on the surfaces of marine algae or invertebrates. Over 400 strains of surface-associated bacteria from various species of seaweed and invertebrate from Scottish coastal waters were isolated and 35% of them shown to produce antimicrobial compounds. This is a much higher proportion than free living marine isolates or soil bacteria. In addition, many strains which did not normally produce antibiotics could be induced to do so by exposing them to small amounts of live cells, supernatants from other bacterial cultures or other chemicals. Thus the number of strains able to produce antibiotics appears to be much higher than previously thought. Induction of antibiotic production was elicited by other marine epibionts and also by terrestrial human pathogens such as Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa. An understanding of this type of chemical induction and the factors regulating non-constitutive secretion of antimicrobial compounds will allow more effective strategies for searching for new chemotherapeutic antibiotics to be designed.     

Transitions in fertility research

History reveals that the genesis of progress in fertility research comes chiefly from animal research, and that subsequent applications of this research to humans have touched on many sensitive beliefs, prejudices, religions, and philosophies. Developments in fertility research, when applied to the human, diverge into two sensitive and very complex applied research categories-assisted reproduction and contraception. History also shows that these concurrently progressing research disciplines have undergone vacillating interludes of progress and of being blocked or restricted. Many of the technological improvements considered to be major transitional states in the progress of each of these categories are identified. They include artificial insemination, the invention of the sheath and the intrauterine device, the identification of hormones, and the elucidation of their activities as well as their interdependent relationships, the social acceptance and rejection, early embryo manipulation techniques, enzyme and sperm capacitation, and certain modern techniques involved in assisted fertility. Giant steps occurred in the 1950's with the rapid and seemingly unrestrained upward movement in chemical and clinical research that produced the hormonal contraceptives. This continued into the 1960's with additional advances providing improvements and popular choices such as intrauterine devices. In the following decades, many improvements were realized in both disciplines; however, changes in the legal environment, the litigious attitude of the public, sources of financial support, and basic priorities by industry and governments have caused uncertainty in many areas. The progressive moves seem to have occurred at certain periods when our population was not preoccupied with other matters and tended to pursue intellect and logic. This paper attempts to summarize a portion of the history of discoveries and developments in fertility research within each of the two applied research categories, and thereby to reveal and discuss a few of the underlying factors and the human qualities that impacted on the evolution of fertility research.     

Male sterility at extreme temperatures: a significant but neglected phenomenon for understanding Drosophila climatic adaptations

The thermal range for viability is quite variable among Drosophila species and it has long been known that these variations are correlated with geographic distribution: temperate species are on average more cold tolerant but more heat sensitive than tropical species. At both ends of their viability range, sterile males have been observed in all species investigated so far. This symmetrical phenomenon restricts the temperature limits within which permanent cultures can be kept in the laboratory. Thermal heat sterility thresholds are very variable across species from 23 degrees C in heat sensitive species up to 31 degrees C in heat tolerant species. In Drosophila melanogaster, genetic variations are observed among geographic populations. Tropical populations are more tolerant to heat induced sterility and recover more rapidly than temperate ones. A genetic analysis revealed that about 50% of the difference observed between natural populations was due to the Y chromosome. Natural populations have not reached a selection limit, however: thermal tolerance was still increased by keeping strains at a high temperature, close to the sterility threshold. On the low temperature side, a symmetrical reverse phenomenon seems to exist: temperate populations are more tolerant to cold than tropical ones. Compared to Mammals, drosophilids exhibit two major differences: first, male sterility occurs not only at high temperature, but also at a low temperature; second, sterility thresholds are not evolutionarily constrained, but highly variable. Altogether, significant and sometimes major genetic variations have been observed between species, between geographic races of the same species, and even between strains kept in the laboratory under different thermal regimes. In each case, it is easily argued that the observed variations correspond to adaptations to climatic conditions, and that male sterility is a significant component of fitness and a target of natural selection.     

Male attitudes towards family planning in Khartoum, Sudan

Knowledge of, attitudes toward, and use of contraception were investigated in a 1982 survey of 250 men living in Khartoum, Sudan. Interviews were conducted at mosques, marketplaces, a government office building, and a textile factory. 75% of respondents were ages 21-40. 92% of respondents expressed the belief that Khartoum is overcrowded, although this was attributed by 57% to rural-urban migration. Despite the fact that 85-95% linked overpopulation with social problems such as inflation, food shortages, and unemployment, 72% expressed a desire for 5 or more children. Only 30% of the men interviewed supported the concept of family size limitation, largely for economic reasons. The majority of those opposing family size limitation cited religious reasons. Attitudes toward child spacing were more favorable, with 80% indicating approval 59% of the men with wives at risk of pregnancy reported that they were using some form of contraception, but only 21% were using an effective method. Two-thirds of respondents reported that they do not discuss contraception with their spouse. 60% identified either the mass media or friends and relatives as their source of family planning information. Although 64% indicated an awarencess of where to obtain family planning services, only 2.8% had ever received services from a family planning clinic. 79% voiced an interest in more information on family planning, and 59% with wives of reproductive age wanted to use family planning services. Most respondents desired more information on sexual sterilization and, although surgical contraception is not available in Sudan, 10% said they would consider this method when they attained their desired family size. The belief that family size should be limited increased dramatically with education, from 9% among those with no formal schooling to 45% among men with 13 or more years of school. Men under 40 years of age had more favorable attitudes toward family planning than older men. Surprisingly, men interviewed at mosques had the most favorable attitudes whereas government employees were the most conservative. Overall, these fndings suggest that the present family planning clinic system in Sudan may be falling short of meeting the demand for information services.     

The Rose Bengal Test in human brucellosis: a neglected test for the diagnosis of a neglected disease

Brucellosis is a highly contagious zoonosis affecting livestock and human beings. The human disease lacks pathognomonic symptoms and laboratory tests are essential for its diagnosis. However, most tests are difficult to implement in the areas and countries were brucellosis is endemic. Here, we compared the simple and cheap Rose Bengal Test (RBT) with serum agglutination, Coombs, competitive ELISA, Brucellacapt, lateral flow immunochromatography for IgM and IgG detection and immunoprecipitation with Brucella proteins. We tested 208 sera from patients with brucellosis proved by bacteriological isolation, 20 contacts with no brucellosis, and 1559 sera of persons with no recent contact or brucellosis symptoms. RBT was highly sensitive in acute and long evolution brucellosis cases and this related to its ability to detect IgM, IgG and IgA, to the absence of prozones, and to the agglutinating activity of blocking IgA at the pH of the test. RBT was also highly specific in the sera of persons with no contact with Brucella. No test in this study outperformed RBT, and none was fully satisfactory in distinguishing contacts from infected patients. When modified to test serum dilutions, a diagnostic titer >4 in RBT resulted in 87.4% sensitivity (infected patients) and 100% specificity (contacts). We discuss the limitations of serological tests in the diagnosis of human brucellosis, particularly in the more chronic forms, and conclude that simplicity and affordability of RBT make it close to the ideal test for small and understaffed hospitals and laboratories.     

Involuntary childlessness: a neglected problem in poor-resource areas

¹ Correspondence address. Nieuwe Prinsengracht 130, Gebouw G, 1018 VZ Amsterdam, The Netherlands. E-mail: f.vanbalen{at}uva.nl/vabalen{at}hotmail.com Childlessness is analysed on the individual, the national andthe international level. On the individual level five categoriesof consequences are described: grief and sadness; social isolationand stigma; restricted rights; religious effects and economicaspects. The first category concerns individual feelings andthe others are socio-cultural effects in broad-sense. In developingcountries childlessness has consequences on individual and socio-culturallevel. In the West consequences are mostly restricted to individualfeelings. In poor-resource areas there are limited possibilitiesfor modern biomedical treatment. Traditional medicine, withits easy access and cultural acceptation, is a serious ‘competitor’.On the national level there are few incentives and possibilitiesfor development of adequate infertility treatment. Though localand national authorities might be sensitive to the problem,allocation of funds is mostly determined by international agencies,which consider other issues more important. On the internationallevel Western perceptions about the urgency of health issuesare still dominant. In the Western world there is little interestand understanding in the problem of ‘barrenness amongplenty’ because a focus on population growth reductionand on other problems. Also, the perception of childlessnessas an individual problem, makes it difficult to change thisattitude. Possibilities for change are discussed.