Where next?

This paper provides a personal perspective on the rich discussions at the Bixby Forum. The size, rate of growth and age structure of the human population interact with many other key factors, from environmental change to governance. While the details of future interactions are sometimes difficult to predict, taken together they pose sombre threats to a socially and economically sustainable future for the rich and to any realistic possibility of lifting the world''s bottom two billion people out of poverty. Adaptive changes will be needed to cope with an ageing population in countries with low fertility or below, but these are achievable. More worrying, continued rapid population growth in many of the least developed countries could lead to hunger, a failure of education to keep pace with growing numbers, and conflict. The assumption that the demographic transition from high to low birth rates occurs as a result of exogenous social and economic forces is being replaced by a clearer understanding of the many barriers that separate women from the knowledge and technologies they need to manage their childbearing within a human rights framework. The forum ended with a clear consensus that much more emphasis needs to be given to meeting the need for family planning and to investing in education.     

Where is APC going?

Adenomatous polyposis coli (APC) protein has been thought to function as a tumor suppressor through its involvement in the Wnt/beta-catenin signaling pathway. However, its connections to the cytoskeleton and microtubules in particular are becoming apparent, and the discovery of these new functions for APC is leading to a reevaluation of its role not only in tumorigenesis, but also in normal physiology.     

Where are the Subtropics?

The tropics are clearly defined while ‘subtropics’ and ‘subtropical’ have been applied to a variety of zones, climates, and ecosystems. However, in the recent terrestrial biology literature, they have been used mainly for the zones between the tropics (±23.4^o C) and ±30.0^o. Adopting this standard would facilitate pan‐subtropical comparisons.     

Where Next for Microbiome Research?

The development of high-throughput sequencing technologies has transformed our capacity to investigate the composition and dynamics of the microbial communities that populate diverse habitats. Over the past decade, these advances have yielded an avalanche of metagenomic data. The current stage of “van Leeuwenhoek”–like cataloguing, as well as functional analyses, will likely accelerate as DNA and RNA sequencing, plus protein and metabolic profiling capacities and computational tools, continue to improve. However, it is time to consider: what’s next for microbiome research? The short pieces included here briefly consider the challenges and opportunities awaiting microbiome research.

This Perspective is part of the “Where next?” Series.

Soon, we will enter an era when “the number of population genomes deposited in public databases will dwarf those from isolates and single cells” (Gene Tyson). Clearly, as all authors noted in the following, our focus will move from describing the composition of microbial communities to elucidating the principles that govern their assembly, dynamics, and functions. How will such principles be discovered? Elhanan Borenstein proposes that a systems biology–based approach, particularly the development of mathematical and computational models of the interactions between the specific community components, will be critical for understanding the function and dynamics of microbiomes. Evolutionary biologists Howard Ochman and Andrew Moeller want to decipher how microbial assemblies evolve but challenge us to also consider the role of microbial communities in organismal evolution, and they make the exciting prediction that microbes will be implicated in the evolution of eusociality and cooperation. Brett Finlay underscores the need for deciphering the mechanistic bases—particularly the chemical/metabolite signals—for interactions between members of microbial communities and their hosts. He emphasizes how this knowledge will enable creation of new tools to manipulate the microbiota, a key challenge for future investigation. Heidi Kong also encourages deciphering the mechanisms that underlie associations between particular skin surfaces and disorders and their respective microbiota. Jeffrey Gordon considers several intriguing opportunities as well as challenges that manipulation of the gut microbiota presents for improved human nutrition and health. Finally, Karen Nelson, Karim Dabbagh and Hamilton Smith suggest that using synthetic genomes to create novel microbes or even synthetic microbiomes offers a new way to engineer the microbiota. Overall, future microbiome research regarding the molecules and mechanisms mediating interactions between members of microbial communities and their hosts should lead to discovery of exciting new biology and transformative therapeutics.     

Where is behavioural ecology going?

Since the 1990s, behavioural ecologists have largely abandoned some traditional areas of interest, such as optimal foraging, but many long-standing challenges remain. Moreover, the core strengths of behavioural ecology, including the use of simple adaptive models to investigate complex biological phenomena, have now been applied to new puzzles outside behaviour. But this strategy comes at a cost. Replication across studies is rare and there have been few tests of the underlying genetic assumptions of adaptive models. Here, I attempt to identify the key outstanding questions in behavioural ecology and suggest that researchers must make greater use of model organisms and evolutionary genetics in order to make substantial progress on these topics.     

Genetic research in osteoporosis: Where are we? Where should we go next?

Fractures resulting from low bone mass and excessive skeletal fragility (osteoporosis) are common worldwide both in males and females, particularly in later years of life. Both fractures, and the most important predictor of fractures, bone mass, are now known to be strongly heritable. This fact, plus the current growth in genetic science, has led to a surge of genetic research in osteoporosis, mostly in the search for genes and their polymorphisms that are responsible for variation in bone mass. Finding the genetic basis underlying variation in bone mass will lead us to deeper understanding of the biology of bone mass accumulation, maintenance and adaptation to load. This, plus finding the genetic basis for overall variation in fracture risk per se, will facilitate the development of interventions, both pharmaceutical and non-pharmaceutical, to prevent and/or treat osteoporosis successfully. This research has produced a rather large number of gene loci that seem to influence bone mass. The challenge now is to refine the statistical genetics and the phenotypes involved so that we can confidently identify those gene loci that truly influence bone mass, and to find ways to study the genetic basis for the most direct disease outcome of interest, fracture.     

Crop biotechnology. Where now?

Nature Biotechnology organized a conference in London on Agobiotech 99: Biotechnology and World Agriculture (November 14-16, 1999). The conference focused entirely on crop biotechnology and covered both societal and scientific aspects. Below is an account of the more important issues raised by the speakers and the audience.     

Vaccines against Tuberculosis: Where Are We and Where Do We Need to Go?

In this review we discuss recent progress in the development, testing, and clinical evaluation of new vaccines against tuberculosis (TB). Over the last 20 years, tremendous progress has been made in TB vaccine research and development: from a pipeline virtually empty of new TB candidate vaccines in the early 1990s, to an era in which a dozen novel TB vaccine candidates have been and are being evaluated in human clinical trials. In addition, innovative approaches are being pursued to further improve existing vaccines, as well as discover new ones. Thus, there is good reason for optimism in the field of TB vaccines that it will be possible to develop better vaccines than BCG, which is still the only vaccine available against TB.     

Where is biological therapy going?

The substantial progress in our understanding of molecular and cellular biology has allowed us to design biological therapeutics ('biologicals') with defined targets and effector functions. These biologicals have greatly contributed to our current knowledge of pathogenetic mechanisms in autoimmune diseases. However, although some of the biologicals have been extremely successful in treating the symptoms of chronic inflammation, biological therapy has not yet met the expectations of permanently silencing the chronic immune response. In this commentary we discuss current concepts and future directions of biological therapy, and the potential usefulness of biologicals as a treatment of human autoimmune diseases in appropriate critical applications with the use of suitably designed agents.