Vaccination today and tomorrow

The vaccines against infectious diseases in use today are, with few exceptions, prepared from the causal agents themselves, either by inactivating them with a chemical such as formaldehyde or by attenuating them so that they grow and thus evoke an immune response in the natural host but cause no disease. These empirical approaches have produced many highly successful vaccines. Increasing knowledge at the molecular level of the agents and of the immune response to protein antigent is now providing us with the opportunity to design vaccines that will elicit protective responses without the need to use the agents themselves. The critical issue is to identify the immune responses that correlate with protection.     

Life sciences today and tomorrow: emerging biotechnologies

The purpose of this review is to survey current, emerging and predicted future biotechnologies which are impacting, or are likely to impact in the future on the life sciences, with a projection for the coming 20 years. This review is intended to discuss current and future technical strategies, and to explore areas of potential growth during the foreseeable future. Information technology approaches have been employed to gather and collate data. Twelve broad categories of biotechnology have been identified which are currently impacting the life sciences and will continue to do so. In some cases, technology areas are being pushed forward by the requirement to deal with contemporary questions such as the need to address the emergence of anti-microbial resistance. In other cases, the biotechnology application is made feasible by advances in allied fields in biophysics (e.g. biosensing) and biochemistry (e.g. bio-imaging). In all cases, the biotechnologies are underpinned by the rapidly advancing fields of information systems, electronic communications and the World Wide Web together with developments in computing power and the capacity to handle extensive biological data. A rationale and narrative is given for the identification of each technology as a growth area. These technologies have been categorized by major applications, and are discussed further. This review highlights:

• Biotechnology has far-reaching applications which impinge on every aspect of human existence.

• The applications of biotechnology are currently wide ranging and will become even more diverse in the future.

• Access to supercomputing facilities and the ability to manipulate large, complex biological datasets, will significantly enhance knowledge and biotechnological development.

     

Proteases and their inhibitors: today and tomorrow.

A major incentive in inhibitor research is that control of limited proteolysis constitutes a valuable pharmacological tool. Protease inhibitors have proved to be successful in influencing pathogenesis in many experimental models but a breakthrough to use in human therapy has mainly been restricted to aprotinin and angiotensin converting enzyme (ACE) inhibitors. However, the success of ACE inhibitors as pharmacological tools in hypertension has proved to be a strong stimulant for new protease inhibitor approaches to drug therapy. While emphasis in the search for next generations of ACE inhibitors may move from the circulation renin-angiotensin system to the local tissue systems, including heart, brain and genital tract, persistent and insightful design of renin inhibitors has already yielded highly specific molecules with potent activities in several in vivo models. The development of orally effective long-acting inhibitors will finally allow an evaluation to be made of their therapeutic profile with regard to the family of ACE inhibitors. The close relationship between renin and HIV-1 protease presents an exceptional opportunity for transfer of the knowledge acquired in renin inhibitor development during the past decade, to an accelerated generation of specific HIV-1 protease inhibitors as effective agents in treatment of AIDS. The self-assembly of 2 identical monomers into a symmetrical structure in HIV-1 protease is not only an elegant way to create an active enzyme while encoding a minimal amount of genetic information, but is also in concordance with the bilobular active-site found in mammalian aspartic proteases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mycobacterium tuberculosis: here today, and here tomorrow

Mycobacterium tuberculosis is a highly successful pathogen that parasitizes the macrophages of its host. Its success can be attributed directly to its ability to manipulate the phagosome that it resides in and to prevent the normal maturation of this organelle into an acidic, hydrolytic compartment. As the macrophage is key to clearing the infection, the interplay between the pathogen and its host cell reflects a constant battle for control.     

H+-PPases: yesterday, today and tomorrow

Suggestions by Calvin about a role of inorganic pyrophosphate (PPi) in early photosynthesis and by Lipmann that PPi may have been the original energy-rich phosphate donor in biological energy conversion, were followed in the mid-1960s by experimental results with isolated chromatophore membranes from the purple photosynthetic bacterium Rhodospirillum rubrum. PPi was shown to be hydrolysed in an uncoupler stimulated reaction by a membrane-bound inorganic pyrophosphatase (PPase), to be formed at the expense of light energy in photophosphorylation and to be utilized as an energy donor for various energy-requiring reactions, as a first known alternative to ATP. This direct link between PPi and photosynthesis led to increasing attention concerning the role of PPi in both early and present biological energy transfer. In the 1970s, the PPase was shown to be a proton pump and to be present also in higher plants. In the 1990s, sequences of H(+)-PPase genes were obtained from plants, protists, bacteria and archaea and two classes of H(+)-PPases differing in K(+) sensitivity were established. Over 200 H(+)-PPase sequences have now been determined. Recent biochemical and biophysical results have led to new progress and questions regarding the H(+)-PPase family, as well as the families of soluble PPases and the inorganic polyphosphatases, which hydrolyse inorganic linear high-molecular-weight polyphosphates (HMW-polyP). Here we will focus attention on the H(+)-PPases, their evolution and putative active site motifs, response to monovalent cations, genetic regulation and some very recent results, based on new methods for obtaining large quantities of purified protein, about their tertiary and quaternary structures.     

Diseases of civilization,today and tomorrow

Summary The term diseases of civilization that would have represented many scourges of the past, now applies to chronic conditions, still of obscure origin, which have replaced them as dominant health problems of the more industrialized countries. The reasons for their emergence include the decline of major epidemic diseases and associated social troubles, and the various consequences of economic development. Both groups of factors are increasingly relevant to the situation in many developing countries, where the expectation of life has been increasing spectacularly for many years, and where changes in the biological, physical and social environment are in progress. The incidence of cardiovascular diseases, cancer and other diseases proceeds gradually and inexorably, and may be hastened by the interaction of old and new risk factors that happen to coexist in some newer industrialized countries. These include: accumulation of environmental pollution, overcrowding in continually growing cities, increase in cigarette smoking, alcohol and fat consumption, and disintegration of the social infrastructure. The interaction of these factors may result in increased incidence, prevalence and mortality from disease of civilization in the now developing world in a few decades to come.

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Resumen El término arriba mencionado, que hubiera descrito en el pasado a muchas enfermadades epidémicas, se refiere ahora a estados crónicos, de origen todavía oscuro, que las han reemplazado como principal problema de tipo sanitario en los países más industrializados. El declive de las enfermedades epidémicas de mayor importancia, con todos los problemas sociales que estas generaban, junto con algunas consecuencias del desarrollo económico, se cuentan entre las causas de este cambio. En los países en vías de desarrollo dos factores tiene una importancia determinante en la evolución de este proceso: el espectacular aumento de la esperanza de vida y los cambios en los entornos biológico, físico y social. Como con consecuencia de todo ello la incidencia de enfermedades cardiovasculares, cáncer y otras enfermedades va incrementádose inexorablemente, acelerándose su aparición debido a la interacción entre factores de riesgo viejos con los nuevos, que coexisten en los países de in industrialización reciente, entre los que cabe incluir: la acumulación de polución ambiental, el hacinamiento en ciudades de constante crecimiento, el incremento en el consumo de cigarrillos, alcohol y grasas, y la desintegración de las estructuras sociales tradicionales. En las próximas décadas, la interacción entre todos factores, puede conducir a un aumento en la tasa de mortalidad por enfermedades de la civilización en el hasta ahora denominado mundo en vías de desarrollo.

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Résumé Le terme de maladies de civilisation, qui pouvait correspondre dans le passé à bien des fléaux; s'applique aujourd'hui à des affections chroniques d'origines encore inconnue qui ont remplacé les anciens fléaux comme problèmes dominants de la santé dans les pays les plus développés. Les raisons de leur émergence comprennent d'une part la disparition des grandes épidémies et d'autres conséquences des vicissitudes sociales, et d'autre part l'interaction de divers sousproduits du développement économique. Ces deux groupes de facteurs concernent un nombre croissant de pays en voie de développement: depuis plusieurs années, la durée de vie moyenne de leurs populations s'est allongée de façon spectaculaire et leur environnement biologique, physique et social est en cours de changement. De ce fait, les maladies cardiovasculaires, le cancer et d'autres affections progressent graduellement et inéluctablement, et cette évolution peut être hâtée par l'interaction des vieux et des nouveaux facteurs de risques qui coexistent chez certains nouveaux venus à la civilisation industrielle. Ces risques comprennent: l'accumulation de la pollution dans l'environnement, la sur-population des mégalopoles qui ne cessent de croître, la consommation accrue de tabac, d'alcool et de graisses, la désintégration de l'infrastructure sociale et bien d'autres facteurs encore. L'accumulation de ces agents agressifs peut conduire à accroître dans les prochaines décennies l'incidence et la prévalence des maladies de civilisation et leur taux de mortalité dans le monde présentemment en cours de développement.

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Invited paper presented at the VII International Conference on the Global Impacts of Applied Microbiology, Helsinki, 12–16.8.1985. Session 4     

Monolithic stationary phases: yesterday, today, and tomorrow

The history of the development of monolithic stationary phases in chromatography, the modem state of the art, and the prospects for their use are considered.     

Electrophoresis today and tomorrow: Helping biologists' dreams come true

Intensive research and development of electrophoresis methodology and instrumentation during past decades has resulted in unique methods widely implemented in bioanalysis. While two‐dimensional electrophoresis and denaturing polyacrylamide gel electrophoresis in sodium dodecylsulfate are still the most frequently used electrophoretic methods applied to analyses of proteins, new miniaturized capillary and microfluidic versions of electromigrational methods have been developed. High‐throughput electrophoretic instruments with hundreds of capillaries for parallel separations and laser‐induced fluorescence detection of labeled DNA strands have been of key importance for the scientific and commercial success of the Human Genome Project. Another powerful method, capillary isoelectric focusing with pressurized and pH‐driven mobilization, provides efficient separations and on‐line sensitive detection of proteins, bacteria and viruses. Electrophoretic microfluidic devices can integrate single‐cell injection, cell lysis, separation of its components and fluorescence or mass spectrometry detection. These miniaturized devices also proved the capability of single‐molecule detection.