Order, disorder, death: lessons from a superorganism

Abstract

Animal models contribute to the understanding of molecular mechanism of cancer, revealing complex roles of altered cellular-signaling networks and deficient surveillance systems. Analogous pathologies are documented in an unconventional model organism that receives attention in research on systems theory, evolution, and aging. The honeybee (Apis mellifera) colony is an advanced integrative unit, a "superorganism" in which order is controlled via complex signaling cascades and surveillance schemes. A facultatively sterile caste, the workers, regulates patterns of growth, differentiation, homeostasis, and death. Workers differentiate into temporal phenotypes in response to dynamic social cues; chemosensory signals that can translate into dramatic physiological responses, including programmed cell death. Temporal worker forms function together, and effectively identify and terminate abnormal colony members ranging from embryos to adults. As long as this regulatory system is operational at a colony level, the unit survives and propagates. However, if the worker phenotypes that collectively govern order become too few or change into malignant forms that bypass control mechanisms to replicate aberrantly; order is replaced by disorder that ultimately leads to the destruction of the society. In this chapter we describe fundamental properties of honeybee social organization, and explore conditions that lead to states of disorder. Our hope is that this chapter will be an inspirational source for ongoing and future work in the field of cancer research.

Fig. 1

The castes of the honeybee. There is only one queen (A) in a honeybee colony. She is the dominant reproductive female and can live up to 3−5 years. The worker (B) is a facultatively sterile female with a typical lifespan of 4−6 weeks. A colony normally consists of 10,000−30,000 worker bees. The male caste, or drone (C), is only raised under favorable conditions when there may be 300−3000 drones present in the society. Few drones survive more than 4−5 weeks.

Fig. 2

The honeybee colony—schematic illustration of a feral nest inside a trunk cavity. The cross-section shows the spatial arrangement of wax-cells of honey at the periphery and a pollen storage close to the central brood nest.

Fig. 3

Differentiation of honeybees castes and further specialization of workers. After hatching, a diploid honeybee larva can either become a worker or a queen. The differentiation depends solely on nourishment provided by adult workers during the first days of larval life. Ample feeding leads to a queen phenotype (A). Newly emerged virgin queens go through a maturation period before they mate and become the dominant reproductive female of a nest. Reduced feeding of larvae leads to a worker phenotype (B). After maturation, the worker enters the temporal nurse bee stage (duration of this stage is typically in the range of 7−40 days). Nurse bees can differentiate into foragers or diutinus workers depending on whether brood is present in the colony. As a forager, the bee collects resources in the field (duration of this stage is about 7−21 days), but may also revert to nest tasks if many nurse bees are removed from the colony. As a diutinus worker, the bee survives for several months (up to 280 days) before she differentiates into a nurse or a forager (Omholt and Amdam, 2004). The males, or drones (C), are haploid and die as soon as they have mated with a virgin queen.

Fig. 4

Regulation of death. The illustrations show the lethal fight between two virgin queens (A), and the excessive coating response of honeybee workers that have targeted an adult individual for termination (B). The undesired individual in the center dies of thermal stress.

Fig. 5

Growth abnormalities in embryos of an inbred strain. Embryos are stained with hematoxylin/eosin. Abnormal development within the egg membrane (A) (photo at 10×) can lead to death of the embryo and the egg never hatches. An older embryo shows severe growth abnormalities (B) (two superimposed photos at 16×) with tumor-like outgrowths (C and D) (close ups at 40×). Resulting larvae may survive for a limited time in vitro (M. Bergem, personal communication). In the colony setting, similar individuals appear to be rapidly killed by adult workers. Image courtesy of Z. L. P. Simôes.

Fig. 6

Embryos that were left untreated or UV irradiated (0.1 second at 1 J/cm²) when 4-hour old (photos at 10×). Untreated honeybee embryos (A) show normal development 54 hours after collection, whereas irradiated embryos (B) after 54 hours develop abnormally. Image courtesy of M. Bergem.

Fig. 7

Normal colony development versus social cancer. The propagation unit for a honeybee colony is the swarm (A). Swarming (splitting) occurs after the colony unit has grown to a certain size. Worker bees produce new queen larvae and prior to the adult emergence of the first virgin, the old queen leaves to find a new colony together with a fraction of the worker population. The malignant A. m. capensis phenotype enters a host nest (B), overrides the control mechanisms of the society, and starts laying diploid eggs by thelytokous parthenogenesis. Gradually the resulting female clones, which do work, break down the social integrity of the society and the host colony perishes. A. m. capensis subsequently disperse in search of new host colonies. In many ways, this process is comparable to metastasis.