Is bigger better?

To close the gap between research and development, a number of funding organizations focus their efforts on large, translations research projects rather than small research teams and individual scientists. Yet, as Paul van Helden argues, if the support for small, investigator-driven research decreases, there will soon be a dearth of novel discoveries for large research groups to explore.What is medical science all about? Surely it is about the value chain, which begins with basic research and ends—if there is an end—with a useful product. There is a widespread perception that scientists do a lot of basic research, but neglect the application of their findings. To remedy this, a number of organizations and philanthropists have become dedicated advocates of applied or translational research and preferentially fund large consortia rather than small teams or individual scientists. Yet, this is only the latest round in the never-ending debate about how to optimize research. The question remains whether large teams, small groups or individuals are better at making ‘discoveries''.To some extent, a scientific breakthrough depends on the nature of the research. Einstein worked largely alone, and the development of E = mc² is a case in point. He put together insights from many researchers to produce his breakthrough, which has subsequently required teams of scientists to apply. Similarly, drug development may require only an individual or a small team to make the initial discovery. However, it needs many individuals to develop a candidate compound and large teams to conduct clinical trials. On the other hand, Darwin could be seen to have worked the other way around: he had an initial ‘team'' of ‘field assistants''—including the crew of HMS Beagle—but he produced his seminal work essentially alone.Consortium funding is of course attractive for researchers because of the time-scale and the amount of money involved. Clinical trials or large research units may get financial support for 10 years or even longer and in the range of millions of dollars. However, organizations that provide funding on such a large scale require extensive and detailed planning from researchers. The work is subject to frequent reporting and review and often carries a large administrative burden. It has come to the point where this oversight threatens academic freedom. Principal investigators who try to conduct experiments outside the original plan, even if they make sense, lose their funding. Under such conditions, administrative officials are often not there to serve, but to govern.There is a widespread perception that small teams are more productive in terms of published papers. But large-scale science often generates outcomes and product value that a small team cannot. We therefore need both. The problem is the low level of funding for individual scientists and small teams and the resulting cut-throat competition for limited resources. This draws too many researchers to large consortia, which, if successful, can become comfort zones or, if they crash and burn, can cause serious damage.Other factors should also inform our deliberations about the size of research teams and consortia. Which is the better environment in which to train the next generation of scientists? By definition, research should question scientific dogmas and foster innovative thinking. Will a large consortium be able to achieve or even tolerate this?Perhaps these trends can be ascribed to generational differences. Neil Howe described people born between 1943 and 1980 as obsessed with values, individually strong and individualistic, whereas the younger folks born after 1981 place more trust in strong institutions that are seen to be moving society somewhere. If this is true, we can predict that the consortium approach is here to stay, at least for some time. Perhaps the emergence of large-scale science is driven by strong—maybe dictatorial—older individuals and arranged to accommodate the younger generation. If so, it is a win–win situation: we know the value of networking and interacting with others, which comes naturally in the ‘online age''.A down side of large groups is the loss of individual career development. The number of authors per paper has increased constantly. Who does the work and who gets the honour? There is often little recognition for the contribution of most people to publications that arise from large consortia, and it is difficult for peer-reviewers to assess individual contribution. We must take care that we measure what we value and not value what we measure.While it is clear that both large and small groups are essential, good management and balance is required. An alarming trend in my opinion is the inclination to fund new sites for clinical trials, to the detriment of existing facilities. This does not seem to be reasonable or the best use of scarce resources.In the long-term interest of science, we need to consider the correlation of major breakthroughs compared to incremental science with the size of the research group. This is hard to measure, but we must not forget that basic research produces the first leads that are then developed further into products. If the funding for basic science decreases, there will soon be a dearth of topics for ‘big science''.Is there a way out of this dilemma? I would like to suggest that organizations currently funding large consortia allow investigators to set aside a percentage of the money to support basic, curiosity-driven research within these consortia. If they do not rethink their funding strategy, these organizations may find with time that there are few novel discoveries for large groups to explore.     

When is bigger better? The effects of group size on the evolution of helping behaviours

Understanding the evolution of sociality in humans and other species requires understanding how selection on social behaviour varies with group size. However, the effects of group size are frequently obscured in the theoretical literature, which often makes assumptions that are at odds with empirical findings. In particular, mechanisms are suggested as supporting large‐scale cooperation when they would in fact rapidly become ineffective with increasing group size. Here we review the literature on the evolution of helping behaviours (cooperation and altruism), and frame it using a simple synthetic model that allows us to delineate how the three main components of the selection pressure on helping must vary with increasing group size. The first component is the marginal benefit of helping to group members, which determines both direct fitness benefits to the actor and indirect fitness benefits to recipients. While this is often assumed to be independent of group size, marginal benefits are in practice likely to be maximal at intermediate group sizes for many types of collective action problems, and will eventually become very small in large groups due to the law of decreasing marginal returns. The second component is the response of social partners on the past play of an actor, which underlies conditional behaviour under repeated social interactions. We argue that under realistic conditions on the transmission of information in a population, this response on past play decreases rapidly with increasing group size so that reciprocity alone (whether direct, indirect, or generalised) cannot sustain cooperation in very large groups. The final component is the relatedness between actor and recipient, which, according to the rules of inheritance, again decreases rapidly with increasing group size. These results explain why helping behaviours in very large social groups are limited to cases where the number of reproducing individuals is small, as in social insects, or where there are social institutions that can promote (possibly through sanctioning) large‐scale cooperation, as in human societies. Finally, we discuss how individually devised institutions can foster the transition from small‐scale to large‐scale cooperative groups in human evolution.     

Benchmarking ontologies: bigger or better?

A scientific ontology is a formal representation of knowledge within a domain, typically including central concepts, their properties, and relations. With the rise of computers and high-throughput data collection, ontologies have become essential to data mining and sharing across communities in the biomedical sciences. Powerful approaches exist for testing the internal consistency of an ontology, but not for assessing the fidelity of its domain representation. We introduce a family of metrics that describe the breadth and depth with which an ontology represents its knowledge domain. We then test these metrics using (1) four of the most common medical ontologies with respect to a corpus of medical documents and (2) seven of the most popular English thesauri with respect to three corpora that sample language from medicine, news, and novels. Here we show that our approach captures the quality of ontological representation and guides efforts to narrow the breach between ontology and collective discourse within a domain. Our results also demonstrate key features of medical ontologies, English thesauri, and discourse from different domains. Medical ontologies have a small intersection, as do English thesauri. Moreover, dialects characteristic of distinct domains vary strikingly as many of the same words are used quite differently in medicine, news, and novels. As ontologies are intended to mirror the state of knowledge, our methods to tighten the fit between ontology and domain will increase their relevance for new areas of biomedical science and improve the accuracy and power of inferences computed across them.     

Feeding and foraging behaviour of a generalist caterpillar: are third instars just bigger versions of firsts?

Similarities and differences in foraging behaviour between first and third instar Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) on Vigna radiata (L.) R. Wilczek (Fabaceae) (mung bean) were determined by frequent, repeated observation of insects on whole plants. The time apportioned to feeding, resting and searching by these two larval instars differed. Third instars were often found feeding on exposed areas of the plant and, if in the terminal parts, would leave these areas more frequently than first instars. Third instars fed at fewer sites and spent less time searching and resting, fed in longer bouts and spent 20% more time feeding than first instars. Although both instars tended to move upwards to the top of the plant, this applied to approximately half of the third instars observed compared to all of the first instars. First instars were found to have a higher relative growth rate than third instars. The results show that it cannot be assumed that first instars are just smaller versions of late instars.     

Membrane simulations: bigger and better?

Molecular dynamics simulations of biological membranes have come of age. Simulations of pure lipid bilayers are extending our understanding of both optimal simulation procedures and the detailed structural dynamics of lipids in these systems. Simulation methods established using simple bilayer-embedded peptides are being extended to a wide range of membrane proteins and membrane protein models, and are beginning to reveal some of the complexities of membrane protein structural dynamics and their relationship to biological function.     

The bigger the healthier: are the limits of BMI risk changing over time?

The body mass index (BMI) is often used as a predictor of overweight and obesity. There is, however, an important debate among international specialists as to what the risk limits should be, and where the cut-off points should be located. In the United States, for instance, adults with a BMI between 25 and 30 are considered overweight, while adults with a BMI of 30 or higher are considered obese. Nevertheless some researchers, especially in developing countries, claim that the limits established for the US are too permissive, and that the threshold to define obese adults should be set lower for other nationalities and ethnicities. This paper analyzes the mortality risks for different BMI levels of two populations of American adult men. The first population lived during the last quarter of the 19th century and the early 20th century. These men were drawn from a random sample of Union Army veterans who fought during the American Civil War (1861-1865). A contemporary sample of men was drawn from the first wave of the National Health and Nutrition Examination Survey (NHANES I) conducted between 1971 and 1975. The results indicate that the frontier of overweight and obesity are expanding over time, such that the potential risk is nowadays associated with higher levels of BMI. The finding may imply that differences in BMI cut-off points are not only cross ethnic, but also occur for similar ethnicities across time.     

Genome size: does bigger mean worse?

Genome sizes vary enormously. This variation in DNA content correlates with effective population size, suggesting that deleterious additions to the genome can accumulate in small populations. On this view, the increased complexity of biological functions associated with large genomes partly reflects evolutionary degeneration.     

A bigger mouse? The rat genome unveiled

Rattus norvegicus is an important experimental organism and interesting to evolutionary biologists. The recently published draft rat genome sequence provides us with insights into both the rat's evolution and its physiology. We learn more about genome evolution and, in particular, the adaptive significance of gene family expansions and the evolution of rodent genomes, which appears to have decelerated since the divergence of mouse and rat. An important observation is that some regions of genomes, many in noncoding regions, show very high sequence conservation, while others show unexpectedly fast evolution. Both of these may be pointers to functional significance.     

Why are organisms usually bigger in colder environments? Making sense of a life history puzzle

Environmental effects on body size are of widespread ecological and economic importance but our understanding of these effects has been obscured by an apparent paradox. Life history analysis suggests that it is adaptive for adults to emerge smaller if reared in conditions that slow down juvenile growth. However, whereas smaller adults emerge if growth is limited by food availability, the reverse is usually observed if growth is limited by temperature. The resolution of this apparent paradox may be that the response of adult size to temperature is adaptive, but is constrained by a trade-off that can be understood in terms of von Bertalanffy's classic theory of growth. Alternatively, the response may be the unavoidable consequence of a fundamental relationship between cell size and temperature.     

Flexing the abdominals: do bigger muscles make better fighters?

Animal contests often involve the use of repeated signals, which are assumed to advertise stamina, and hence fighting ability. While an individual may be predicted to give up once it has crossed an energetic threshold, costs inflicted by its opponent may also contribute to the giving-up decision. Therefore, physical strength should be of key importance in contests, allowing high signal magnitude as well as potentially inflicting costs. We investigated this using hermit crab shell fights, which employ a 'hybrid signal' of shell rapping, which advertises stamina but also imposes potentially deleterious consequences for the receiver. We examined the links between contest outcomes and two proxies for strength; the protein content and relative mass of hermit crab abdominal muscles, the main muscle group used in shell rapping. Our results indicate that there was no difference in muscle protein between winners and losers, whereas winners had significantly greater muscle mass : body mass ratios. Thus, while stamina has been assumed by theory to be an important determinant of agonistic success, the present results demonstrate the importance of muscle size and thereby strength.     

Egg size variation in birds with asynchronous hatching: is bigger really better?

In many animals large size at birth enhances offspring survival, but comparative evidence remains equivocal for birds. Failure to consider asynchronous hatching (ASH) may have confounded previous analyses. We assessed effects of egg size and ASH on growth and survival of common grackle (Quiscalus quiscula) nestlings to test the hypothesis that females adjust the size of last-laid eggs to modify effects of ASH. Although positive, the effect of egg size on nestling growth and survival was overwhelmed by the effect of ASH, with late-hatched nestlings being most likely to starve. Egg size did significantly affect growth late in the nestling period, but only because starvation had greatly reduced hatching asynchrony among surviving nestlings. Similarly, in experimentally synchronized nests, egg size and hatching asynchrony both affected offspring growth early in the nestling phase. Our results suggest that there is unlikely to be an adaptive advantage to females from varying the size of last-laid eggs in species with substantial ASH and that studies to assess the effect of a given maternal effect (e.g., varying egg size) should be done in the context of other maternal effects that may be operating simultaneously (e.g., ASH).     

Is bigger better? The relationship between size and reproduction in female Asian elephants

The limited availability of resources is predicted to impose trade‐offs between growth, reproduction and self‐maintenance in animals. However, although some studies have shown that early reproduction suppresses growth, reproduction positively correlates with size in others. We use detailed records from a large population of semi‐captive elephants in Myanmar to assess the relationships between size (height and weight), reproduction and survival in female Asian elephants, a species characterized by slow, costly life history. Although female height gain during the growth period overlapped little with reproductive onset in the population, there was large variation in age at first reproduction and only 81% of final weight had been reached by peak age of reproduction at the population level (19 years). Those females beginning reproduction early tended to be taller and lighter later in life, although these trends were not significant. We found that taller females were more likely to have reproduced by a given age, but such effects diminished with age, suggesting there may be a size threshold to reproduction which is especially important in young females. Because size was not linked with female survival during reproductive ages, the diminishing effect of height on reproduction with age is unlikely to be due to biased survival of larger females. We conclude that although reproduction may not always impose significant costs on growth, height may be a limiting factor to reproduction in young female Asian elephants, which could have important implications considering their birth rates are low and peak reproduction is young – 19 years in this population.     

Is bigger better? A possibility for adaptation of <Emphasis Type="Italic">Daphnia</Emphasis> to filamentous cyanobacteria in the face of global warming

Body size is a key determinant of fitness in Daphnia. Bigger size means higher feeding efficiency and reproduction. However, filamentous cyanobacteria have a more detrimental effect on larger daphnids. Predicted global warming is expected to reduce size of Daphnia and facilitate frequent occurrence of cyanobacteria. Therefore, we asked two questions: (i) does elevated temperature cause reduced size of daphnids, and (ii) is temperature-dependent size reduction adaptive in an environment dominated by filamentous cyanobacteria? To address these issues, we obtained 8 clones of the Daphnia longispina complex from artificially heated lakes and 8 clones from control lakes, and exposed them to a favorable food Scenedesmus obliquus and a mixture of S. obliquus and the filamentous cyanobacterium Cylindrospermopsis raciborskii in life table experiments at 16, 20, and 24°C. Individuals from heated lakes attained larger body size than those from control lakes. Moreover, exposure to the filamentous cyanobacterium led to reduced fecundity of Daphnia from the non-heated lakes and did not affect reproduction of Daphnia from the heated lakes. We conclude that Daphnia display some evolutionary adaptations to cope with filamentous cyanobacteria, linked to long-term exposition to elevated temperature. Our results violate broadly accepted assumptions that ectotherms are smaller in warmer environments.