Recently, the fruit fly Drosophila melanogaster has been introduced as a model system to study the molecular bases of a variety of ethanol-induced behaviors. It became immediately apparent that the behavioral changes elicited by acute ethanol exposure are remarkably similar in flies and mammals. Flies show signs of acute intoxication, which range from locomotor stimulation at low doses to complete sedation at higher doses and they develop tolerance upon intermittent ethanol exposure. Genetic screens for mutants with altered responsiveness to ethanol have been carried out and a few of the disrupted genes have been identified. This analysis, while still in its early stages, has already revealed some surprising molecular parallels with mammals. The availability of powerful tools for genetic manipulation in Drosophila, together with the high degree of conservation at the genomic level, make Drosophila a promising model organism to study the mechanism by which ethanol regulates behavior and the mechanisms underlying the organism's adaptation to long-term ethanol exposure.

Ethanol is an important environmental variable for fruit-breeding Drosophila species, serving as a resource at low levels and a toxin at high levels. The first step of ethanol metabolism, the conversion of ethanol to acetaldehyde, is catalyzed primarily by the enzyme alcohol dehydrogenase (ADH). The second step, the oxidation of acetaldehyde to acetate, has been a source of controversy, with some authors arguing that it is carried out primarily by ADH itself, rather than a separate aldehyde dehydrogenase (ALDH) as in mammals. We review recent evidence that ALDH plays an important role in ethanol metabolism in Drosophila. In support of this view, we report that D. melanogaster populations maintained on ethanol-supplemented media evolved higher activity of ALDH, as well as of ADH. We have also tentatively identified the structural gene responsible for the majority of ALDH activity in D. melanogaster. We hypothesize that variation in ALDH activity may make an important contribution to the observed wide variation in ethanol tolerance within and among Drosophila species.

Understanding the evolutionary ecology of ethanol production may yield insights into why humans are prone to excessive consumption of ethanol. In particular, Dudley (2000) suggested that human ancestors developed a genetically based attraction to ethanol because they could use its odor plume to locate fruiting trees and because of health benefits from its consumption. If so, ethanol should be common in wild fruits and frugivores should prefer fruits with higher ethanol content. A literature review reveals that ethanol is indeed common in wild fruits but that it typically occurs in very low concentrations. Furthermore, frugivores strongly prefer ripe over rotting fruits, even though the latter may contain more ethanol. (Data on ethanol content of ripe and rotting wild fruit are lacking.) These results cast doubt on Dudley's hypothesis and raise the question of how humans became exposed to sufficiently high concentrations of ethanol to allow its excessive consumption. Because fermentation is an ancient and widespread practice, I suggest that humans “discovered” ethanol while using fermentation as a food preservation technique. They may have been predisposed to consume ethanol from previous and beneficial exposure to much lower doses or they may have become addicted to it at high concentrations because of fortuitous physiological responses.

In this paper we discuss how yeast, fungi ubiquitously present in sugar-rich fruit, can influence the interaction between frugivores and fleshy-fruited plants via ethanol. We suggest that plants, the seeds of which are mostly dispersed by vertebrates, exploit the ethanol from alcoholic fermentation by yeast in their seed dispersal strategy. Moderate consumption of ethanol, i.e., at concentrations close to those in naturally ripening fruit, by frugivores may have beneficial short- and long-term effects for these potential dispersers, whereas consumption of larger quantities may have negative short- and long-term effects. Ethanol vapor emanating from palatable fruit may act as an odor cue, guiding bats and other frugivores to the fruit, and aiding them to assess its quality. In addition, we suggest that ingested ethanol may be an appetitive stimulant. We also evaluate the possibility that ethanol within fruit may be used as a source of energy by frugivorous vertebrates. Our preliminary data indicate that Egyptian fruit bats (Rousettus aegyptiacus) can use the odor of ethanol to assess food suitability, but also that it may not serve as an attractant over short distances (i.e., <1 m). Instead, ethanol is avoided at concentrations greater than 1%, a value which might typically characterize overripe and otherwise unpalatable fruit. Our initial results further indicate that Egyptian fruit bats significantly decrease their food consumption if it contains 1 or 2% ethanol. Overall, ethanol may play diverse roles in the nutritional ecology and behavior of fruit-eating bats, and in the interaction between frugivores and plants, in general.

Survival and reproductive success hinge on the perception of environmental stimuli. In this regard, foraging efficiency depends on discerning predictive signals in food. A widespread occurrence of ethanol in fruits indicates a sustained historical exposure of frugivores to this compound. Accordingly, Dudley (2000, Quart. Rev. Biol. 75:3–15) proposed that ethanol could represent a prominent sensory cue to primates because of direct and indirectly associated caloric and physiological rewards. However, little is known regarding the extent to which ethanol correlates with such parameters. This information is essential to estimating the importance of detecting and detoxifying ethanol in fruits. Here I present a preliminary analysis of fruits from Southeast Asia; low levels of ethanol were present in fruits of all developmental stages (range: 0.005–0.48%). Moreover, ethanol correlated positively with concentrations of soluble sugars, suggesting that it could be a valuable foraging cue. Recent findings on the sensitivity of primate olfaction and gustation to ethanol are consistent with this notion. However, when primates smell fruits deliberately, it often occurs together with digital and/or dental evaluation of texture. Here I show that softening texture also characterizes the fruit ripening process, and that color is of ambiguous importance to primates possessing trichromatic vision. I discuss the relevance of these findings to the origins of primates and the ecology of key sensory systems and deduce that detecting and selecting fruits on the basis of cues other than color is a persistent theme in primate evolution. Ethanol has likely played a significant and underestimated role in the regulation of primate foraging behavior.

Humans and apes are placed together in the superfamily Hominoidea. The evolutionary trajectory of hominoids is intimately bound up with the exploitation of ripe, fleshy fruits. Fermentation of fruit sugars by yeasts produces a number of alcohols, particularly ethanol. Because of their pre-human frugivorous dietary heritage, it has been hypothesized that humans may show pre-existing sensory biases associating ethanol with nutritional rewards. This factor, in turn, could influence contemporary patterns of human ethanol use. At present, there seems little evidence to support a view of selection specifically for ethanol detection or its utilization over the course of hominoid evolution. Ethanol concentration in wild fruits consumed by monkeys and apes is predicted to be low. Wild monkeys and apes avoid consumption of over-ripe fruits, the class showing notable ethanol concentrations, and for this reason, ethanol plumes may act as deterrents rather than attractants. Any energetic benefits to wild primates from ingested ethanol appear negligible, at best. Mice and rats show patterns of ethanol self-administration similar to humans, indicating that a frugivorous dietary heritage is not necessary for such behaviors. In the natural environment, ethanol is predicted to be just one of many alcohols, esters and related compounds routinely encountered by frugivorous primates and of no particular significance. The strong attraction ethanol holds for some individuals could be due to a broad range of genetic and environmental factors. In some humans, the appetite for ethanol appears related to the appetite for sugar. The predisposition some individuals display toward excessive ethanol consumption could involve features of their genetics and biochemical similarities of ethanol and carbohydrate. Regular low ethanol intake is hypothesized to lower the incidence of cardiovascular disease in humans, perhaps through its effects on body fat distribution. Such a benefit, if confirmed, would appear to relate to features of the contemporary human rather than pre-human diet.

Ethanol is a naturally occurring substance resulting from the fermentation by yeast of fruit sugars. The association between yeasts and angiosperms dates to the Cretaceous, and dietary exposure of diverse frugivorous taxa to ethanol is similarly ancient. Ethanol plumes can potentially be used to localize ripe fruit, and consumption of low-concentration ethanol within fruit may act as a feeding stimulant. Ripe and over-ripe fruits of the Neotropical palm Astrocaryum standleyanum contained ethanol within the pulp at concentrations averaging 0.9% and 4.5%, respectively. Fruit ripening was associated with significant changes in color, puncture resistance, sugar, and ethanol content. Natural consumption rates of ethanol via frugivory and associated blood levels are not known for any animal taxon. However, behavioral responses to ethanol may have been the target of natural selection for all frugivorous species, including many primates and the hominoid lineages ancestral to modern humans. Pre-existing sensory biases associating this ancient psychoactive compound with nutritional reward might accordingly underlie contemporary patterns of alcohol consumption and abuse.

The substantial medical risks of heavy alcohol drinking as well as the existence of a safe drinking limit have been evident for centuries. Modern epidemiologic studies also show lower risk of both morbidity and mortality among lighter drinkers. Defining “heavy” as ≥3 standard drinks per day, the alcohol–mortality relationship is a J-curve with risk highest for heavy drinkers, lowest for light drinkers and intermediate for abstainers. A number of non-cardiovascular and cardiovascular problems contribute to the increased mortality risk of heavier drinkers. The lower risk of light drinkers is due mostly to lower risk of the most common cardiovascular condition, coronary heart disease (CHD). Thus, disparate relationships of alcoholic drinking to various cardiovascular and non-cardiovascular conditions constitute a modern concept of alcohol and health. Increased cardiovascular risks of heavy drinking include: 1) alcoholic cardiomyopathy, 2) systemic hypertension (high blood pressure), 3) heart rhythm disturbances in binge drinkers, and 4) hemorrhagic stroke. Lighter drinking is unrelated to increased risk of any cardiovascular condition and, in observational studies, is consistently related to lower risk of CHD and ischemic stroke. A protective hypothesis for CHD is robustly supported by evidence for plausible biological mechanisms attributable to ethyl alcohol. International comparisons and some prospective study data suggest that wine is more protective against CHD than liquor or beer. Possible non-alcohol beneficial components in wine (especially red) support possible extra protection by wine, but a healthier pattern of drinking or more favorable risk traits in wine drinkers may also be involved.