Alcohol in Human Evolution

The Raw and the Rotten (9)

Where I grew up, Fresno, California, one of the joys of winter was the arrival of the cedar waxwings, which, I believe, are North America’s most subtly beautiful birds. At that time of year waxwings rely on small berries for sustenance. They are not finicky as to the kinds of berries consumed. In more natural areas they rely on native species, particularly toyon; in less natural areas such as my then front yard, non-native species do just fine. In suburban California generally, exotic pepper trees and pyracantha offer good pickings. Like the native toyon (nicknamed Christmas berry) both of those non-natives retain their red berries through the winter. We had a large pyracantha bush that was much appreciated by the cedar waxwings.

By late winter, though, the pyracantha berries were past their sell by date; they had begun to ferment. The kind of fermentation these berries underwent was different than those described in the previous chapter, one in which alcohol, rather than lactic acid was a primary byproduct. Alcoholic fermentations are caused primarily by yeasts of various sorts.

Yeasts are single celled fungi, devolved from multicellular fungi, such as molds and mushrooms. This reductive evolution occurred several times, independently, over the last billion years. The yeasts involved in alcoholic fermentations all derive from one of these transitions from the multicellular to the unicellular. Of these, some of the most proficient belong to the genus, Saccharomyces, (Sack-a-row-my-seas) Latin for “sugar fungus”.

Alcoholic fermentations generally produce a variety of alcohols the best known of which is ethanol. The waxwings were consuming small amounts of ethanol with each of the fermenting pyracantha berries they swallowed. Though I did not know it then, the alcohol in these fermented berries caused these birds to become intoxicated, which retrospectively explained the aberrant behavior I observed, most notably and depressingly a penchant to fly into immovable objects, such as my house. Not, like some other birds, the windows of the house, but the solid walls. Also, automobiles and the very ground itself. Many years after I left Fresno I was not surprised to read about a case of mass mortality events among similarly intoxicated waxwings in southern California. Such are the perils of flying while intoxicated.

But not always. South and Central American Leaf-nosed bats (family Phyllostomidae)--so called because of a leaf-like structure on the face that focuses echolocation signals—include a wide variety of dietary specialists. There are some species that dine primarily on insects, some on frogs, some on fruit, some on nectar, and most notoriously, some on blood (vampire bats). Those that focus primarily on fruits or nectar ingest quite a lot of ethanol with their meals because of yeast activities. But they are completely unimpaired with respect to both flight and echolocation at blood alcohol levels nearly twice that at which Americans are considered legally drunk  10.1371/journal.pone.0008993.

What the leaf-nosed bats have, and the cedar waxwings lack, is alcohol tolerance. Animal species, from insects to primates vary widely in their alcohol tolerance. Most of this variation is related to how much of the food they eat has been altered by yeasts. Fruit and nectar are the food sources most likely to be yeast-impacted, and hence alcoholic. Other plant and all animal foods are not at all alcoholic. So, it’s not surprising that animals that eat a lot of fruit (called frugivores) and nectar (called nectivores) tend to be more alcohol tolerant the pure herbivores or pure carnivores. Omnivores are all over the map.

Alcohol tolerance is influenced by a host of enzymes. In mammals, most reside in the liver. The first step in alcohol metabolism is the conversion of alcohol molecules to another class of organic molecules called aldehydes. Aldehydes are further converted to other biochemicals, ultimately to acetate.  (Recall that acetate is one of the short chain fatty acids produced by both internal and external lactic acid fermentation.)

Alcohol tolerance is largely a function of the efficiency of these first steps in alcohol metabolism. One group of enzymes involved in the first step are called alcohol dehydrogenases (ADHs). Of these, ADH4 (also called ADH7) has been studied in the broadest range of species. One recent genomic survey of mammals is particularly informative https://doi.org/10.1098/rsos.230451. (see also, http://dx.doi.org/10.1098/rsbl.2020.0070 )

All mammals have the ADH4 gene, but in many it is non-functional because of various mutations that have disabled it. This often happens in evolution when a gene becomes superfluous. Among those mammals with non-functional ADH4 are all herbivores and carnivores, neither of which are likely to encounter ethanol in their diets. Most rodents, all bats, and all primates, on the other hand, retain functional ADH4.

With respect to primates, Robert Dudley traces alcohol tolerance to a time 40 million years ago, when fruit became an important dietary element in the Old-World lineage. This is called the Drunken Monkey Hypothesis. The idea is that in their search for ripe fruit our distant primate ancestors also encountered overripe fruit and hence ethanol. Ethanol is calorically rich, much more so than any carbohydrates in the fruits, including glucose, sucrose, and fructose. So, some or all frugivorous primates may have evolved an attraction to alcohol. Fruit-eating primates are generally arboreal. So, on this view, alcohol tolerance would mean fewer monkeys falling out of trees 10.3390/nu13072419.

But most of the overripe fruit that’s still on the tree contains no alcohol; even the ripest is in the early phase of alcoholic fermentation. So, it’s not clear how much alcohol tolerance these monkeys would have required. Generally, the really overripe fruits have fallen to the ground. Our more recent ancestors began spending more time on the ground about 10 million years ago, at which point they would have been exposed to fruit with higher alcohol content. Within a week, some fallen fruits contain over 3% alcohol by volume.

As it happens, a mutation in the ADH4 gene occurred in our more grounded ancestors at this time, one which increased the rate of conversion of alcohol to aldehyde 40-fold. We share this mutation with African great apes. Matthew Carrigan, who discovered the mutation claims that it is the root of our exceptional alcohol tolerance 10.1073/pnas.1404167111. The ADH4 mutation occurred at about the same time as the HCA3 mutation discussed earlier, which seems to have evolved in response to increased consumption of lactic acid fermented foods. Katherine Amato thinks the timing is not coincidental. She claims both are evidence for our longstanding adaptation to fermented foods that began when our ancestors descended from the trees and encountered new food sources 10.1086/715238.

We Are Not Alone

Even the alcohol tolerant animals like us and chimps become intoxicated if we consume too much but the effects are much more transitory than in the non-alcohol tolerant. Human inebriation is commonplace in modern society, probably not so much in our foraging ancestors. It may have happened occasionally though, judging by chimps in West Africa.  Some enterprising individuals have learned to steal fermenting palm sap from human palm sap tappers. The human natives--there and in many other parts of the old-world tropics-- collect the sweet sap of several palm species to make palm wine. In some parts of West Africa chimps have also acquired a taste for palm wine, which they procure with characteristic chimp ingenuity: They crush large plant leaves to sop up sap from the tap. Sometimes they sop up so much that they show every indication of intoxication  10.1098/rsos.150150. But the blood alcohol levels of a drunken chimp--or human, for that matter--would be sufficient to kill most other creatures on this earth.

One of the exceptions is the aye-aye, a phantasmagoric creature. It is certainly recognized as such in its native Madagascar, where it is the source of many superstitions.  The aye-aye belongs to a primitive group of primates called lemurs. They are not at all typical lemurs, though. Most lemurs are incredibly cute. My son slept with stuffed versions of several species. But no Aye-Ayes. They look spooky, the stuff of nightmares.  Aye-Ayes have large eyes, even larger ears of bat-like proportions, and even larger tails that rival those of giant anteaters, proportionally. But most distinctive and downright creepy are their extremely long fingers, much like those of E.T. (I wouldn’t be surprised if aye-ayes were an inspiration for E.T.). The middle finger is the longest, and aye-ayes use it in multiple ways. They often deploy the finger to extract insect larvae—detected by those large ears-- from the bark of trees. But aye-ayes also use their E.T. finger to extract palm sap. And they are not fussy as to its freshness. Much of the palm sap they consume is fermented to 3% alcohol or more, yet aye-ayes can still acrobatically navigate the forest canopy. Aye-ayes too have the modified ADH4 gene, though independently evolved /10.1098/rsos.160217.

Making Our Own

When did our ancestors begin to begin to manage alcoholic fermentation? And what were the raw materials? Everyone agrees that it began accidentally. There is less agreement regarding the raw materials. Many believe it was honey. But mead is an improbable candidate for the first deliberately concocted alcoholic beverage.

First, raw honey is simply too valuable to deliberately let rot. It is perhaps the most energy dense food known to humankind. Where available it can provide a significant amount of the total calories consumed by foragers. For the Hadza of East Africa, up to 15% of their calories are provided by honey; they consider honey the most delicious and coveted element of their diets.

The Hadza go to great lengths to procure honey, sometimes working perilously, over 100 feet above ground, on a baobab tree while fighting off what have come to be known as killer bees. Killer bees originated in Africa, their aggressiveness evolved in no small part because of human predation on their hives. (The honey badger (ratel), which is also a hive menace, seems invulnerable to bee stings as it does to all other forms of physical insults including those from cobras and lions.) Given the extreme value of raw honey, any Hadza who tried to make mead would be immediately exiled. Nor is there any evidence that any other contemporary foragers who collect honey ever make mead.

Mead has other disadvantages, mostly related to the unique challenges honey presents to wild yeasts. The problems for the yeasts are threefold. The first probably stems from the fact that for millions of years the interests of bees and yeasts did not at all coincide. Quite the opposite, in fact. Fermentation had been an ongoing threat to bee colonies, essentially spoiling the food supply for developing larvae. Honeybees “solved” this problem by making honey too sugary for the sugar fungus. The bees take nectar that is over 80% water and through metabolic alchemy turn it into honey that is only 12-14% water, rendering it yeast proof.

When yeasts find themselves in the viscous gunk that is honey, they face a problem called osmotic stress. Osmosis is simply the process whereby water flows along a gradient from higher to lower concentrations. Yeasts, like all living things, are mostly water, which means that when immersed in an extremely dehydrated environment, such as that of honey, the water is sucked out of them. In essence, they implode. This is why mead making requires the addition of lots of water to the honey; only when the honey is extremely diluted can fermentation begin.

Once the osmotic problem was solved, fermentation could proceed, but stopped well before all the sugar is consumed, resulting in a sweet low alcohol concoction. In modern parlance this is referred to as a stuck fermentation. Honey fermentations generally get stuck because honey is low in essential yeast nutrients. The modern solution is to add these nutrients, including vitamins, periodically during the fermentation. Our forager ancestors eventually solved the problem through the addition of wild fruits and grains, which provided the yeast enough nutrients to raise the alcohol levels considerably. Patrick McGovern refers to these augmented meads as grogs. https://www.amazon.com/s?k=9780520944688&i=stripbooks&linkCode=qs

The fruit adjuncts also helped solve the third challenge honey presents to a yeast: a high ratio of fructose to glucose. Yeasts love glucose--fructose, not so much. Yeast can ferment fructose but do so much more slowly. Fruit contains much more glucose and less fructose than honey. So, fruit adjuncts would help increase alcohol levels in the final product and speed up the fermentation process. But fermentation would still be slow, much slower, certainly, than a ferment of pure overripe fruit, which, as we have seen, is how humans encountered ethanol in the first place.

Pure honey takes months to fully ferment, fruit, nectar, and sap take hours to days. It seems unlikely that foragers would have the time or patience to haul around fermenting mead for extended periods. Much quicker to make fruit wines, simply by collecting the juice of fermenting fruits. Honey probably came to be added later in more settled societies. In that context, enough honey could be accumulated for some to be set aside for fermentation into mead. Most likely this mead was reserved for elites.

Vinegar Flies

Though it wasn’t in the form of mead, alcoholic fermentation was managed to varying degrees during the Pleistocene, long before the onset of farming. Important evidence for pre-agricultural deliberate alcoholic fermentation comes from our long-standing association with a tiny insect, a species of fruit fly (Drosophila melanogaster) known as the vinegar fly. Vinegar flies also loves overripe fruit and have evolved remarkable alcohol tolerance as a result. In fact, this species has become alcohol dependent. In the lab, fruit flies exposed to ethanol aerosols live longer than those that are not. https://doi.org/10.4161/cib.3.4.11885 

Today, vinegar flies can be found worldwide but it was not always thus. Their cosmopolitan distribution stems from their longstanding association with humans, called commensalism, which began with foragers making fruit wines in southern Africa.

The vinegar fly is but one of many species of fruit flies of varied lifestyles. Many are attracted to ripe fruit, others to overripe fruit. The latter group have evolved alcohol tolerance, none more so than vinegar flies. This is the species you will encounter if you go to a winery during the crush. It is also the species you will encounter if you let your bananas turn brown. Originally, though, vinegar flies specialized on just one type of fruit, the marula, coveted by humans and elephants alike https://doi.org/10.1016/j.cub.2018.10.033. (Apocryphal legends of elephants drunk on fermenting marula are spread by safari operators throughout southern Africa.)

Vinegar flies are native to southern Africa. And there they long remained, until they began exploiting human marula foragers. Their initial exploitation was confined to their ancestral homeland, where the ancestors of today’s San peoples dwelled. Then, as now, the marula fruit was a highly sought-after food during the South African spring. Rock paintings indicate that they were collected and stored in caves in large quantities. Some caves contain millions of marula seeds, which are about the size of a walnut.

There was much too much marula fruit to be eaten fresh, or even slightly rotten. Rather, as is true of marula gatherers today, the fruit juices would be accumulated in calabashes and other gourds and left to spontaneously ferment into marula wine. Today, marula wine left to ferment 2-4 days has an alcohol content of 3-5%. When higher alcohol levels are sought, the fermentation is longer. The shelf life of marula wine is longer than that of marula fruit, especially if stored in cool caves. The marula wine also contains, in addition to ethanol, many nutrients that are absent in the raw fruit. Plus, it promotes conviviality.

This large source of fermenting marula fruit is what got vinegar flies hooked on humans. But first they had to overcome a behavioral barrier—a strong disinclination to enter dark places that is common to all species of fruit flies. That they did overcome this phobia is indicated by a recent experiment in their native range. Vinegar flies have a sister species also from the same area, which, however, prefers ripe to overripe fruit and is not alcohol tolerant. When both fresh and rotting fruit was placed in the dark recesses of a cave, vinegar flies soon entered, the sister species, however, remained outside. The vinegar flies’ evolved tolerance of darkness was an important step in their human exploitation.  https://portal.research.lu.se/en/publications/idrosophilai-sensory-neuroethology.

But if vinegar flies remained marula specialists, they weren’t going to exploit humans outside of the marula’s range. To expand their range and fully take advantage of what humans had to offer, they needed to acquire a taste for other fruit. To this end, whatever chemical odorants the vinegar flies found attractive had to expand beyond those produced by marula. (Today, oranges are a particular favorite wherever grown.) Once the vinegar flies became less specialized on marula, their range expanded to other parts of Africa where foragers harvested and stored other kinds of fruits.  From Africa they spread to Eurasia and eventually every part of the world where overripe fruit was made available by human foragers and eventually, farmers.

While wines were the first alcoholic fermented beverages that we imbibed, it was two other products of alcoholic fermentation—beer and bread—that led us down the path to agriculture.