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June 20, 2018

Three drinks for the ages

Filed under: Alcohol,Coffee,Genetics,milk,science — Razib Khan @ 9:33 pm
Irish Coffee

The “Irish coffee” is a a delicious concoction. Coffee, alcohol, and dairy. What more can you ask for? Man does not live on bread and water alone. Cafes and bars are thick on the ground in large cities, but also grace country roads. Coffee and alcohol are congenial to conviviality among settled peoples, while milk is the staff of life for many pastoralists, consumed raw or turned into cheese.


Of the three, coffee is a new on the scene, discovered within the past 1,000 years. The consumption of milk, whether raw or as cheese, goes back to prehistory. But on the geological scale it a recent cultural development. In contrast, the imbibing of alcohol in some form is probably as old as humanity itself, albeit not as a pint in the pub.

Alcohol is produced naturally by the fermentation process, a metabolic pathway which is far more ancient than the oxygen metabolism that has been dominant for the past few billion years. Humans are omnivores, and our ancestors consumed overripe fruit which had fermented to the point of producing alcohol byproduct. Meanwhile, “good bacteria” in our guts also produced alcohol.

This is not a bad thing. Alcohol is nutritious in that it provides calories.

Though in modern societies we “count our calories”, and the richness of a deep and dark beer is not always a selling point, for the vast majority of our species’ history those calories were a feature, not a bug.

Early civilization ran on beer. The Sumerians even had a goddess of beer, Ninkasi. The workers who built the pyramids of Old Kingdom Egypt were given rations of beer. In other words, the wonders of the ancient world were fueled by alcohol!

And this is not just forgotten history. Until very recently much of the world was awash in alcohol, whether it be beer, wine, or various distilled spirits. Public and private drunkenness were one of the major reasons behind the emergence of the American “temperance” movement. Though Prohibition was deemed a failure, American alcohol consumption has never recovered to its earlier highs.

One of the reasons that Americans, and many other peoples, drank so much is that alcoholic beverages is that not only did they provide calories, but they were often more potable than conventional water. Ancient humans in hunter-gatherer bands did not have to contend to cholera, but the first village societies, and those who lived in early modern cities, lacked modern sanitation. Safe drinking water was one of the major achievements of 20th century engineering, and obviated the role that alcohol had traditionally played in quenching the thirst of the common man.

But alcohol is not a matter just of history, biochemistry and engineering. Humans differ in their ability and capacity to metabolize alcohol due to variation on their genes. In particular, ADH and ALDH2. The ADH genes produce enzymes which breakdown alcohol for processing by later biochemical steps, one of which is catalyzed by the product of the ALDH2 gene.

If you’ve ever seen someone with the flushed face characteristic of having had too much to drink, they may have a mutation on ALDH2 which means that they don’t process acetaldehyde very well. As the cells build up acetaldehyde, a host of physiological reactions kick in. Research has shown that those who exhibit these reactions are much less likely to be alcoholic.

In contrast, those with mutations on ADH tend to process alcohol very well indeed. But in the process they produce more acetaldehyde than the body can handle, resulting in physical discomfort. And similarly to the ALDH2 mutation these individuals are less likely to become alcoholic.

Genetic variation in the ability to process alcohol is a consequence of the long history of human omnivory. In contrast, the evolutionary history around our consumption of milk is much more straightforward and strange. For the vast majority of our species’ existence adults have not had the ability to digest milk sugar, lactose. This is a characteristic we share with all other mammals. The adaptive reason for this is likely that it encourages and forces weaning, so that mothers can bear other offspring.

And yet a minority of modern human adults today can digest milk. How? Why? The LCT gene produces an enzyme lactase, and mutations in this gene allow humans in Europe, parts of Southern Asia, East Africa and the Near East to continue to drink milk into adulthood. Over the past 5,000 years unique mutations in Europe and South Asia, in Arabia, and in Africa, have all been strongly selected.

In Denmark the mutant allele is now at frequencies as high as 90%.

Ancient DNA tells us that the ability to digest milk sugar into adulthood did not arise with agriculture and sedentary lifestyles. It is not implausible that Neolithic people who domesticated goats and sheep fermented milk to produce cheeses, where the sugar was broken down to make it more palatable. But the adaptation to a predominantly dairy dependent lifestyle only emerged with full-blown pastoralism, over the past 4,000 years. The earliest pastoralists on the Bronze Age Eurasian steppe carried the lactase persistent genetic variant, but only at low frequencies.

Dairy is an essential part of the modern food pyramid, at least for the USDA. But perhaps it tells us more about our evolutionary present than the evolutionary past. So often we talk about evolution as a dynamic of the deep past. But with lactose tolerance we see evolution as a process which is just initiating.

Finally, there is coffee. Though variation on the CYP1A2, Cytochrome P450, effects how fast caffeine is metabolized, coffee is such a recent cultural invention that it is unlikely that there are any adaptive dynamics related to it on a genetic level. Rather, CYP1A2 is locus which controls processes designed to cope with toxic chemicals by breaking them down. Caffeine in some ways is such a chemical, and those who metabolize it fast need to drink more coffee to feel its effects than those who have more efficient metabolization.

The effect of caffeine on humans is literally inefficiencies of bodily detoxification.

Milk nourishes. Alcohol both nourishes and alters the mental state of those who imbibe it. In contrast, caffeine does not nourish, but stimulates. For the past few million years our species likely never interacted with caffeine, but we were pre-adapted because of our consumption of a wide range of plants which manufacture chemical defenses.

The legend of coffee dates back 1,000 years, when an Ethiopian goatherd saw one of his animals behave strangely after eating a coffee plant. Within the next five hundred years coffee beans were cultivated across the hillocks of the lands around the Red Sea, from Ethiopia to Yemen, and became part and parcel of Islamic culture. To this day the coffeehouse is a major social and cultural nexus in the Middle East, though colonialism has taken it far afield, from Java to Colombia.

By the Renaissance coffee had reached Europe, and the proliferation of coffeehouses, and their stimulative effects, may have triggered the early modern Enlightenment intellectual revolution. While alcohol softens and dims the outlines of world around you, coffee is a stimulant which sharpens our perceptions and accelerates our cognitive pace.

Coffee, alcohol, and milk, are such central aspects modern culture that it is hard to imagine our existence without them. Though there is genetic variation in how we can process them, their relevance to our lives transcends biology, and extends to economics, history, anthropology, and in the case of wine, religion. Though they may not be the ambrosia of the gods, modern civilization arguably stands on the shoulders of these beverages.

Wondering if you are lactose tolerant based on your genetics? Check out Metabolism by Insitome.

Three drinks for the ages was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

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