C. Athena Aktipis

Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms

Microbes in the gastrointestinal tract are under selective pressure to manipulate host eating behavior to increase their fitness, sometimes at the expense of host fitness. Microbes may do this through two potential strategies: (i) generating cravings for foods that they specialize on or foods that suppress their competitors, or (ii) inducing dysphoria until we eat foods that enhance their fitness. We review several potential mechanisms for microbial control over eating behavior including microbial influence on reward and satiety pathways, production of toxins that alter mood, changes to receptors including taste receptors, and hijacking of the vagus nerve, the neural axis between the gut and the brain. We also review the evidence for alternative explanations for cravings and unhealthy eating behavior. Because microbiota are easily manipulatable by prebiotics, probiotics, antibiotics, fecal transplants, and dietary changes, altering our microbiota offers a tractable approach to otherwise intractable problems of obesity and unhealthy eating.

Cancer across the tree of life: cooperation and cheating in multicellularity

Multicellularity is characterized by cooperation among cells for the development, maintenance and reproduction of the multicellular organism. Cancer can be viewed as cheating within this cooperative multicellular system. Complex multicellularity, and the cooperation underlying it, has evolved independently multiple times. We review the existing literature on cancer and cancer-like phenomena across life, not only focusing on complex multicellularity but also reviewing cancer-like phenomena across the tree of life more broadly. We find that cancer is characterized by a breakdown of the central features of cooperation that characterize multicellularity, including cheating in proliferation inhibition, cell death, division of labour, resource allocation and extracellular environment maintenance (which we term the five foundations of multicellularity). Cheating on division of labour, exhibited by a lack of differentiation and disorganized cell masses, has been observed in all forms of multicellularity. This suggests that deregulation of differentiation is a fundamental and universal aspect of carcinogenesis that may be underappreciated in cancer biology. Understanding cancer as a breakdown of multicellular cooperation provides novel insights into cancer hallmarks and suggests a set of assays and biomarkers that can be applied across species and characterize the fundamental requirements for generating a cancer.

Evolutionary foundations for cancer biology

New applications of evolutionary biology are transforming our understanding of cancer. The articles in this special issue provide many specific examples, such as microorganisms inducing cancers, the significance of within‐tumor heterogeneity, and the possibility that lower dose chemotherapy may sometimes promote longer survival. Underlying these specific advances is a large‐scale transformation, as cancer research incorporates evolutionary methods into its toolkit, and asks new evolutionary questions about why we are vulnerable to cancer. Evolution explains why cancer exists at all, how neoplasms grow, why cancer is remarkably rare, and why it occurs despite powerful cancer suppression mechanisms. Cancer exists because of somatic selection; mutations in somatic cells result in some dividing faster than others, in some cases generating neoplasms. Neoplasms grow, or do not, in complex cellular ecosystems. Cancer is relatively rare because of natural selection; our genomes were derived disproportionally from individuals with effective mechanisms for suppressing cancer. Cancer occurs nonetheless for the same six evolutionary reasons that explain why we remain vulnerable to other diseases. These four principles—cancers evolve by somatic selection, neoplasms grow in complex ecosystems, natural selection has shaped powerful cancer defenses, and the limitations of those defenses have evolutionary explanations—provide a foundation for understanding, preventing, and treating cancer.

Overlooking Evolution: A Systematic Analysis of Cancer Relapse and Therapeutic Resistance Research

Cancer therapy selects for cancer cells resistant to treatment, a process that is fundamentally evolutionary. To what extent, however, is the evolutionary perspective employed in research on therapeutic resistance and relapse? We analyzed 6,228 papers on therapeutic resistance and/or relapse in cancers and found that the use of evolution terms in abstracts has remained at about 1% since the 1980s. However, detailed coding of 22 recent papers revealed a higher proportion of papers using evolutionary methods or evolutionary theory, although this number is still less than 10%. Despite the fact that relapse and therapeutic resistance is essentially an evolutionary process, it appears that this framework has not permeated research. This represents an unrealized opportunity for advances in research on therapeutic resistance.

Dispersal Evolution in Neoplasms: The Role of Disregulated Metabolism in the Evolution of Cell Motility

Here, we apply the theoretical framework of dispersal evolution to understand the emergence of invasive and metastatic cells. We investigate whether the dysregulated metabolism characteristic of cancer cells may play a causal role in selection for cell motility, and thus to the tissue invasion and metastasis that define cancer. With an agent-based computational model, we show that cells with higher metabolism evolve to have higher rates of movement and that “neoplastic” cells with higher metabolism rates are able to persist in a population of “normal” cells with low metabolic rates, but only if increased metabolism is accompanied by increased motility. This is true even when the cost of motility is high. These findings suggest that higher rates of cell metabolism lead to selection for motile cells in premalignant neoplasms, which may preadapt cells for subsequent invasion and metastasis. This has important implications for understanding the progression of cancer from less invasive to more invasive cell types. Cancer Prev Res; 5(2); 266–75. ©2011 AACR.

Recognition Memory and the Evolution of Cooperation: How Simple Strategies Succeed in an Agent-Based World

Recent approaches to understanding the cognitive mechanisms underlying decision processes sug gest that simple strategies can result in successful and adaptive behaviors. Here, the evolutionary suc cess of simple recognition memory is investigated. Agents have a limited memory capacity for either agents who have previously cooperated (C-Mem) or those that have previously defected (D-Mem). Various aspects of the ecological and social environment influence the success of each of these strat egies. These findings suggest that recognition memory can play a role in promoting the evolution of cooperation, but that the effectiveness of such a simple recognition memory strategy depends on the fit between that strategy and the (ecological and social) environment in which that strategy is employed. The D-Mem strategy is able to invade only when the memory size of these agents is close to the total number of defectors in the population. However, the C-Mem strategy can invade a popula tion of defectors when memory size is one, as long as the population size is relatively small and the ecological environment promotes longer intervals between each reproductive opportunity.

Fetal microchimerism and maternal health: A review and evolutionary analysis of cooperation and conflict beyond the womb

The presence of fetal cells has been associated with both positive and negative effects on maternal health. These paradoxical effects may be due to the fact that maternal and offspring fitness interests are aligned in certain domains and conflicting in others, which may have led to the evolution of fetal microchimeric phenotypes that can manipulate maternal tissues. We use cooperation and conflict theory to generate testable predictions about domains in which fetal microchimerism may enhance maternal health and those in which it may be detrimental. This framework suggests that fetal cells may function both to contribute to maternal somatic maintenance (e.g. wound healing) and to manipulate maternal physiology to enhance resource transmission to offspring (e.g. enhancing milk production). In this review, we use an evolutionary framework to make testable predictions about the role of fetal microchimerism in lactation, thyroid function, autoimmune disease, cancer and maternal emotional, and psychological health.

An evolutionary explanation for the presence of cancer nonstem cells in neoplasms

Contrary to conventional views that assume all cells in a neoplasm can propagate the tumor, the cancer stem cell hypothesis posits that only a fraction of the cells (the cancer stem cells) can act as tumor‐propagating cells, while most of the tumor is composed of cells with limited replication potential. Here, we offer an evolutionary approach to this controversy. We used several evolutionary, computational models to investigate cancer cell dynamics and conditions consistent with the stem cell hypothesis. Our models predict that if selection acts at the cell level, neoplasms should be primarily comprised of cancer stem cells, in contrast to experimental data indicating that neoplasms contain large fractions of cancer nonstem cells. We explore several solutions explaining the paradoxical existence of cancer nonstem cells in neoplasms, including the possibility that selection acts at the level of multicellular proliferative units.

IS HOMO ECONOMICUS

The awarding in October of 2002 of the Nobel Memorial Prize in Economics 1 Technically the Bank of Sweden Prize in Economic Sciences in Memory of Alfred Nobel, established in 1968.1 to Daniel Kahneman and Vernon Smith might have profound implications for the survival of Homo economicus, which has long occupied a privileged place in the minds of economists and decision-making theorists. The species has endured many challenges and proven quite adaptable, changing to accommodate a cascade of findings inconsistent with its original conception. Homo economicus now faces a potentially more serious challenge: the resurgence of Homo sapiens, a more coherent and biologically grounded model for human decision-making, informed by theory and data from across the scientific spectrum.

Opinion: Control vs. eradication: Applying infectious disease treatment strategies to cancer

Clinical treatment for metastatic cancer has traditionally entailed administering the highest possible dose in the shortest period, a strategy known as high-dose density therapy. The implicit goal is complete eradication. Unfortunately, a systemic cure for most metastatic cancers remains elusive, and the role of chemotherapy has been reduced to prolonging life and ameliorating symptoms.