Entering the 21st century: the challenges for development

By many people, the 20th century will be remembered as an era of great achievement in human endeavour, and of enormous economic growth and prosperity. Achievements in medical research, from eradicating infectious diseases to laser surgery; in engineering, from the transistor to space exploration; and in economic development have all contributed to greater well being in the world at the end of the 20th century. Among the challenges to development identified by the World Bank in the coming decades will be managing the twin processes of globalization and localization, as well as post-conflict reconstruction. These will form the backdrop of the Bank''s main focus of creating a world free of poverty.     

Oxysterols: novel biologic roles for the 21st century

A major focus for the 21st century are the sterol intermediates in cholesterol synthesis and their metabolites. No longer considered inactive way stations in their transformation to cholesterol, both physiologic and pathophysiologic studies, though early in their development, indicate novel biologic roles for these sterols, and their oxysterol metabolites that bypass cholesterol, the expected end product. A major impetus for further inquiry is the recognition that in genetically determined errors in cholesterol synthesis such as Smith-Lemil-Opitz syndrome, the phenotypic effects on the developing fetus are not solely attributable to the lack of cholesterol but the accumulation of 7-dehydrocholesterol and its 27-hydroxy metabolite. This view is now supported by a new mouse model, the double knockout Insig1 & 2 (insulin-induced genes 1 & 2) in which lack of the protein product results in a greater production of lanosterol compared to cholesterol during fetal life with severe dysmorphic consequences. Further support can be derived from in vitro studies of the Sonic hedgehog signaling pathway, essential for normal morphogenesis in the central nervous system and perhaps other organs, which may require the local presence of oxysterols for full expression. Future studies that can delineate the specific role of a sterol intermediate or its metabolite require a paradigm shift away from the generic use of oxysterols as a class of compounds to a focus on specific sterols that can be expected in tissues and techniques for mimicking the local environment. Another class of oxysterols are those arising by photoxidation, now considered to be an expected event generated by the photons of visible blue light and therefore pari passu with normal vision. The sequence of events from peroxides of cholesterol to hydroxy and keto derivatives is the signature of singlet oxygen as opposed to free radicals and other mechanisms for generating reactive oxygen species. Perhaps surprisingly, the retina expresses CYP 27A1 and CYP 46A1, enzymes with broad substrate specificity for ring-modified sterols, implying that, in addition to a rich blood supply for disposing of potentially toxic oxysterols, they can be detoxified locally. Recognition that the retina has nuclear receptors similar to those found in other tissues raises the possibility that the sterols that are generated may function in their traditional role as ligands for modulating gene expression but other, nonligand, activities can be expected since other proteins such as the oxysterol-binding proteins exist and are considered to have biologic activities. To critically evaluate these potentially new biologic roles for oxysterols a need exists for the synthesis and utilization of the expected naturally occurring metabolites rather than available surrogates that may not be truly representative of their tissue effects and to utilize analytical techniques that can identify their existence at the expected concentrations in tissues.     

Green revolution: preparing for the 21st century.

In the 1960s there were large-scale concerns about the world's ability to feed itself. However, widespread adoption of "green revolution" technology led to major increases in food-grain production. Between 1966 and 1990, the population of the densely populated low-income countries grew by 80%, but food production more than doubled. The technological advance that led to the dramatic achievements in world food production over the last 30 years was the development of high-yielding varieties of wheat and rice. These varieties are responsive to fertilizer inputs, are lodging resistant, and their yield potential is 2-3 times that of varieties available prior to the green revolution. In addition, these varieties have multiple resistance to diseases and insects and thus have yield stability. The development of irrigation facilities, the availability of inorganic fertilizers, and benign government policies have all facilitated the adoption of green-revolution technology. In the 1990s, the rate of growth in food-grain production has been lower than the rate of growth in population. If this trend is not reversed, serious food shortages will occur in the next century. To meet the challenge of feeding 8 billion people by 2020, we have to prepare now and develop the technology for raising farm productivity. We have to develop cereal cultivars with higher yield potential and greater yield stability. We must also develop strategies for integrated nutrient management, integrated pest management, and efficient utilization of water and soil resources.     

Tropical medicine for the 21st century.

The specialty of tropical medicine originated from the needs of the colonial era and is removed from many of the health care requirements of tropical countries today. Tropical medicine concentrates on parasitic diseases of warm climates, although other infections and diseases related to poverty rather than climate dominate medicine in developing countries challenged by population pressure, civil strife, and migration. In the new century, tropical medicine would best be absorbed into the specialty of infectious diseases, which should incorporate parasitic diseases, travel medicine, and sexually transmitted diseases. Pressing questions for health care and research in developing countries concern the provision of appropriate services for problems such as HIV/AIDS, tuberculosis, sexually transmitted diseases, and injuries. The question of how to provide appropriate clinical care in resource poor settings for the major causes of morbidity and premature mortality has been neglected by donors, academic institutions, and traditional tropical medicine.     

Biotechnology in the 21st century

Although the future is unpredictable, it is highly likely that biotechnology will play a much more visible and significant role in the 21st century than it did in the 20th century. The number and kinds of drugs provided by biotechnology will expand markedly and biotechnology will stand at the center of the oncoming revolution in bioinformatics.     

Engineering toxins for 21st century therapies

'Engineering Toxins for 21st Century Therapies' (9-10 September 2010) was part of the Royal Society International Seminar series held at the Kavli International Centre, UK. Participants were assembled from a range of disciplines (academic, industry, regulatory, public health) to discuss the future potential of toxin-based therapies. The meeting explored how the current structural and mechanistic knowledge of toxins could be used to engineer future toxin-based therapies. To date, significant progress has been made in the design of novel recombinant biologics based on domains of natural toxins, engineered to exhibit advantageous properties. The meeting concluded, firstly that future product development vitally required the appropriate combination of creativity and innovation that can come from the academic, biotechnology and pharma sectors. Second, that continued investigation into understanding the basic science of the toxins and their targets was essential in order to develop new opportunities for the existing products and to create new products with enhanced properties. Finally, it was concluded that the clinical potential for development of novel biologics based on toxin domains was evident.     

21st century zoo design

A review of Conservation Centres for the New Millennium. Proceedings of the 5^th International Symposium on Zoo Design, edited by Amy B. Plowman and Peter M.C. Stevens. Paignton, Devon, U.K.: Whitely Wildlife Conservation Trust, 1999, 181 pp., paperback.     

Orchid biology: from Linnaeus via Darwin to the 21st century

Orchidaceae are the largest family of flowering plants, with at least 24 000 species, and perhaps better than any other family of flowering plants, orchids represent the extreme specializations that are possible. As a result, they have long fascinated luminaries of the botanical world including Linnaeus and Darwin, but the size of the family has historically been an impediment to their study. Specifically, the lack of detailed information about relationships within the family made it difficult to formulate explicit evolutionary hypotheses for such a large group, but the advent of molecular systematics has revolutionized our understanding of the orchids. Their complex life histories make orchids particularly vulnerable to environmental change, and as result many are now threatened with extinction. In this Special Issue we present a series of 20 papers on orchid biology ranging from phylogenetics, floral evolutionary development, taxonomy, mycorrhizal associations, pollination biology, population genetics and conservation.     

Molecules to minds: grand challenges for the 21st century

The Institute of Medicine's Forum on Neuroscience and Nervous System Disorders established a "Grand Challenges Initiative." The goal is to help frame a broad, integrated research program that would attract substantial funding and generate additional resources to support large-scale efforts to tackle some of the most daunting but important neuroscience questions.