We argue that making accept/reject decisions on scientific hypotheses, including a recent call for changing the canonical alpha level from p = 0.05 to p = 0.005, is deleterious for the finding of new discoveries and the progress of science. Given that blanket and variable alpha levels both are problematic, it is sensible to dispense with significance testing altogether. There are alternatives that address study design and sample size much more directly than significance testing does; but none of the statistical tools should be taken as the new magic method giving clear-cut mechanical answers. Inference should not be based on single studies at all, but on cumulative evidence from multiple independent studies. When evaluating the strength of the evidence, we should consider, for example, auxiliary assumptions, the strength of the experimental design, and implications for applications. To boil all this down to a binary decision based on a p-value threshold of 0.05, 0.01, 0.005, or anything else, is not acceptable.

Resistance-conferring mutations in dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) in Plasmodium falciparum are selected by treatment with sulfadoxine pyrimethamine (SP). We assessed the association between these mutations and transmission capacity of parasites to Anopheles mosquitoes on the Pacific coast of Colombia. Patients with uncomplicated P. falciparum malaria received SP treatment and were followed-up to compare the prevalence of DHFR and DHPS mutations before and after SP treatment. Membrane feeding assays were used to measure infectivity to mosquitoes of post-treatment gametocytes with and without these mutations. Per-protocol treatment efficacy was 95.0% (132 of 139). Gametocytes carrying resistance-conferring mutations were selected after SP treatment and were infective to mosquitoes. Seven days after treatment, infections with two DHFR mutations had a 10-fold higher probability of infecting mosquitoes than infections with no DHFR mutations (odds ratio = 10.23, P< 0.05). Low-level drug resistance mutations have the potential to enhance transmission of P. falciparum and spread resistant parasites.

We argue that making accept/reject decisions on scientific hypotheses, including a recent call for changing the canonical alpha level from p= .05 to .005, is deleterious for the finding of new discoveries and the progress of science. Given that blanket and variable alpha levels both are problematic, it is sensible to dispense with significance testing altogether. There are alternatives that address study design and sample size much more directly than significance testing does; but none of the statistical tools should be taken as the new magic method giving clear-cut mechanical answers. Inference should not be based on single studies at all, but on cumulative evidence from multiple independent studies. When evaluating the strength of the evidence, we should consider, for example, auxiliary assumptions, the strength of the experimental design, and implications for applications. To boil all this down to a binary decision based on a p-value threshold of .05, .01, .005, or anything else, is not acceptable.

Evolutionary robotics allows biologists to test hypotheses about extinct animals. In our case, we modeled some of the first vertebrates, jawless fishes, in order to study the evolution of the trait after which vertebrates are named: vertebrae. We tested the hypothesis that vertebrae are an adaptation for enhanced feeding and fleeing performance. We created a population of autonomous embodied robots, Preyro, in which the number of vertebrae, N, were free to evolve. In addition, two other traits, the span of the caudal fin, b, and the predator detection threshold, ζ, a proxy for the lateral line sensory system, were also allowed to evolve. These three traits were chosen because they evolved early in vertebrates , are all potentially important in feeding and fleeing, and vary in form among species. Preyro took on individual identities in a given generation as defined by the population's six diploid genotypes, G i. Each G i was a 3-tuple, with each element an integer specifying N, b, and ζ. The small size of the population allowed for genetic drift to operate in concert with random mutation and mating; the presence of these mechanisms of chance provided an opportunity for N to evolve by accident. The presence of three evolvable traits provided an opportunity for direct selection on b and/or ζ to evolve N as a by-product of trait correlation. In selection trials, different G i embodied in Preyro attempted to feed at a light source and then flee to avoid a predator robot in pursuit.The fitness of each G i was calculated from five different types of performance: speed, acceleration, distance to the light, distance to the predator, and the number of predator escapes initiated. In each generation, we measured the selection differential, the selection gradient, the strength of chance, and the indirect correlation selection gradient. These metrics allowed us to understand the relative contributions of the three mechanisms: direct selection, chance, and indirect selection. Direct selection on N, operating alone, caused the initial increase in N, but was then augmented by chance and indirect selection.Through the course of 11 generations, chance and indirect selection would occasionally supplant direct selection as the primary evolutionary driver. In later generations, direct selection switched sign, stabilizing N at an apparent optimum mean value of 5.7. These results tentatively support the hypothesis that vertebrae evolved as an adaptation for enhanced feeding and fleeing performance in early vertebrates.

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