How Fermented Milk Products Facilitated an Adaptive Change in the Human Genome

The Raw and the Rotten (9)

One of the most dubious elements of the paleodiet is the proscription of dairy products. The rational, as always, is that dairy products were not consumed by paleolithic foragers. Though the paleodiet advocates are wrong about the paleolithic consumption of grass grains, even as manufactured into bread and beer, they are quite right that dairy products were not consumed until the advent of farming. So what? It is obvious that the human genome has evolved in response to raw animal milk. Moreover, we can trace, in some detail how and when this adaptation occurred, in diverse dairying peoples, from northern Europe to Northern Africa. Moreover, those of us, me included, who lack this adaptation to raw milk, can still enjoy the many benefits of milk in its fermented forms.

Milk is the ultimate superfood. Ask any infant; or rather, watch any infant; watch it grow. No other food on earth can make it grow like that. This is true of all mammals, whether human, whale, or goat. Milk is uniquely mammalian. It contains lots of protein, almost as much protein as mammal meat. There are also abundant fats, essential to a balanced diet. Vitamin D abounds; there is no better source save the sun. Vitamin D is especially important in those regions, such as northern Europe, where the sun is not much in evidence for many months of the year. Milk is also a great source of calcium, essential for strong bones. Raw milk also contains abundant water, an important source of hydration in arid parts of the world.

The problem with raw milk, for many, is the sugar called lactose. This is not a problem for infants of course, only adults who have no dairying in their ancestry. The first milkers had this lactose problem. Fermentation solved it. Before we delve into the fermentation solution, let’s see how we came to acquire milk from non-human mothers. It started with the domestication of goats, sheep, and cattle.

What is Domestication?

There are many misconceptions about domestication, whether plant, animal, or microbe. Most believe that domestication begins when humans take control of breeding, which is called artificial selection. If that were the case, virtually all house cats would be considered undomesticated, because, as is true of their wild ancestors, virtually all domestic cats mate with whomever they damn well please. Cat domestication began over 9,000 years ago, when some found the house mice infesting early granaries easy pickings. This “self-domestication” is not unique to cats. Virtually all domesticated animals are self-domesticated to some extent because they have an active role in exploiting humans. Self-domestication occurs through natural selection, because of the benefits enjoyed by those that opt for human environments relative to those that don’t. 

What about plants? Wheat isn’t active in the way that cats are but there is a sense in which wheats participated in their own domestication. Wheat strains that evolved characters that humans found desirable, such as larger seeds, benefited when in human-dominated environments. (Now that the whole earth is human dominated it is obvious they made the right “choice”.) It is certainly true, however, that humans generally took control of plant breeding earlier in the domestication process than they did that of animals; that is, plants generally experienced artificial selection earlier in the domestication process than most animals. Microbes, as we shall see, are even more self-domesticated than animals. But let’s return to animals.

Even a cursory review of the literature indicates that most archaeologists believe that sheep, goats, cattle, and pigs were domesticated by farmers, that is, plant cultivators. (An exception is Melanie Zeder.) On this view, beginning about 1,000 years after plant cultivation had progressed in earnest, goats, sheep, cattle, and pigs began hanging around human settlements, attracted by the new source of food. Habituation ensued, and a certain degree of tameness. The timing couldn’t have been better, as the farmers had virtually eradicated their favorite prey: gazelles. So, the farmers, seizing on the opportunity to acquire a new source of meat then began to manage the new arrivals, selectively culling young males, eventually confining all.

There is much to recommend this story, particularly as it applies to pigs. But problems arise with respect to the future milk-providers. The wild goats and sheep did not live in the areas where farming was most developed—the lowlands of the southern Levant and the upper Tigris-Euphrates Basin. They preferred the highlands, particularly the Taurus and Zagros mountains of southeastern Turkey, northern Iraq and southwestern Iran, much of the present-day homeland of the Kurds. That is where, according to most archaezoologists, the domestication of sheep and goats began. The early phase of cattle domestication is more mysterious but southeastern Turkey is considered the epicenter. Cayonu, an agricultural mega-settlement in southeastern Turkey is where goats, sheep, cattle, and pigs could first be found together.

By what means, and with whom, did goats, sheep and cattle initiate this new relationship with humans?  As in the above story, it began with herd management and selective culling. But the cullers were not farmers, they were foragers.

Horses provides an example of domestication by foragers that practiced no cultivation. The Botai of central Asia are widely acknowledged to be among the first to domesticate horses around 5,000 years ago. (Subsequently, the ancestors of most domestic horses were independently domesticated elsewhere in the steppes.) The Botai were settled foragers who specialized on hunting horses, which is no easy feat on foot. They learned how to funnel horse herds into temporary enclosures. Initially they probably slaughtered the horses indiscriminately but eventually they began to selectively cull young males, to ensure a more constant food supply. The next step was more permanent enclosures of herds, from which they selected the most docile foals. Eventually, they learned to ride the tame ones, a feat of huge historical consequence. The Botai remained horse hunters even while they were domesticating them. In fact, they became even more efficient horse hunters, using their mounts to approach more closely, chase and herd their prey. The process of the proto-domestic horses, no doubt facilitated the taming of the wild ones. The Botai may also have been the first horse milkers, and the first to ferment mare’s milk into a mild alcoholic drink called koumiss.

Reindeer are currently in the early phase of domestication—at least two independent domestications—by former reindeer hunters that have become reindeer herders. And in some cases—such as the Sami of Northern Scandinavia—milkers. The reindeer milk is consumed both fresh and fermented; it is said to make a yogurt superior to that of cattle. Camel domestication—both Bactrian and dromedary, was similarly achieved by camel hunters cum herders and milkers. Southern Arabia, where dromedary camels were domesticated, and the Northeast Asian steppes, where Bactrian camels were domesticated, never supported much plant cultivation.

It seems quite likely that the domestication of goats, sheep and cattle began with forager-herders, even as wheat, barley and legumes were being simultaneously domesticated by forager-farmers. It is certainly true, though, that in contrast to horses, camels and reindeer, the farmers took over the domestication of this trio—as well as pigs—after which the domestication process accelerated. In the West, we associate milking with farming, but milk is equally, if not more important, to numerous pastoralist societies worldwide, who practice a far from settled existence and minimal plant cultivation. These pastoralists provide support for the recent hypothesis that milk, as much as meat, was the motivation behind the initial management of the milk trio by semi-sedentary foragers. Meat is a very minor component of the diet of many pastoralists; instead, the animal component of their diet is mostly milk.

The milk first hypothesis is a significant departure from the traditional view, according to which the herders initially managed goats, sheep, and cattle for their flesh—both meat and fat. So too, on this view, did the farmers once they got involved. Eventually, after thousands of years, all three species came to be as much valued for what Sherratt calls their secondary products. For cattle it was traction and milk; for goats and sheep it was milk and hides. Of the three, cattle came to produce the most milk by far, followed by sheep and goats.

According to Sherratt, this “secondary products revolution” began around 5,000 years ago, initiating the Bronze Age in the Near East. It is now clear, however, that the use of secondary products began much earlier. The first evidence of milk consumption comes from 8,500-year-old pottery shards from northwestern Anatolia. Pottery is convenient for chemical residue analyses, from which the original contents can be inferred. Indeed, without pottery we would never have known when early milk, and later, wine, was consumed. It is therefore significant that the very first pottery was produced around 8,500 BP. Since the first pottery contained milk products, the consumption of milk products must have extended further back in time, to the pre-pottery era, perhaps as far back as the hunter-herders.

Why the attraction to milk when meat is so much more straight-forwardly obtained? Most fundamentally, milk is a more renewable resource than meat, as present-day pastoralists would universally attest. Nutritionally, milk exceeds meat in many ways. If, that is, you can digest it. And there’s the rub. The first milkers almost certainly could not digest raw milk; even today, most adults worldwide cannot. It’s not just that the nutrients are not absorbed, rather, milk nutrients, along with anything else that was consumed with the meal, are explosively emitted and with some alacrity. The problem is the sugar lactose.

Lactose is not a problem for infants, of course, unless you are a whale or a seal. (The milk of marine mammal contains no lactose but massively more fats.) The lactose content of milk, along with other components, varies widely among mammals. Human milk is at the very high end, far higher than any of the milk trio. The reason human infants can thrive on such high lactose milk is an enzyme, called lactase, which cleaves lactose, a disaccharide, into glucose and galactose, two monosaccharides, simple sugars that can be easily digested. This enzyme is active in infants, but gradually downregulated after weaning. Unfortunately for the lactose intolerant like me who live in a mostly lactose tolerant population, it takes a while to figure out that your lactase has been downregulated. For me, the eureka moment occurred under the worst of circumstances, a high school date.

The first milkers would have been able to diagnose the problem much more quickly. A simple solution today is to let the milk sit and sour. It can be drunk as such or easily converted into a yogurt. The souring occurs when lactic acid bacteria convert lactose to lactic acid. But from whence the LAB?  The first lactic acid bacteria to find themselves in milk had never experienced the sugar lactose, until humans created an environment in which milk existed outside of its direct transmission from mother to infant.  This may seem curious, given the fact that this whole group of bacteria came to be named for what some species did to milk.

The Latin word lac literally means milk. It is the root for lactose, lactase, lactate, and lactic acid. But lactic acid is produced by LAB from many other food sources than milk, mostly plants. In fact, the first LAB species to evolve adaptations for the new milk environment were derived from ancestors that rotted plants, probably grasses. This adaptation probably occurred extremely rapidly given the rate at which bacteria can evolve in novel environments.

Consider a recently documented case of LAB domestication on the other side of the world and in a completely different environment—Amazonia. Until the 1950s and 1960s the Shaur—a Jivaroan people—lived a semi-nomadic existence as forager-farmers in the northern Amazon of Ecuador. They were among the most decentralized of foragers, living in highly dispersed dwellings consisting only of immediate family members. Several of these dispersed family units comprised a band. The Shaur were once notorious for creating shrunken head effigies of their enemies, a practice that offended the sensibilities of the Spanish invaders and which they eventually suppressed. Spanish missionaries also succeeded in making Catholics of them, of sorts. The Shaur generally find Catholicism compatible with their traditional animism, and the traditional methods for warding off evil spirits are still practiced, along with an occasional prayer to the Virgin Mary.

The Shaur were largely able to maintain their way of life in other ways as well. They hunted and fished. In addition, they cultivated several domesticated crops, the most important of which was manioc (cassava, also called yuca). They moved frequently as is typical of Amazonian forager-farmers. Beginning in the 1950s, though, they came to occupy permanently settled villages.

Manioc beer, made from the tuberous roots, was the most significant source of nutrients, and remains so to this day. The manioc tuber is an unlikely food source because it contains abundant cyanide. The species of manioc available to the Shaur is particularly toxic, so it must be extensively processed prior to consumption. It begins with paring or shaving of slices of manioc. The slices are then placed in a pot and boiled. That removes some of the cyanide. More leaches out when the boiled bits are allowed to soak. After a good soak it is ready for fermentation. into a low alcohol beer, called chicha. Most of the alcohol is provided by the yeast. But as in all traditional beers, including early European brews, manioc beer is also an acidic beer. The most important of the acid fermenters are several species of lactic acid bacteria (LAB) but acetic acid bacteria (AAB) are present as well.

As is true of any beer the manioc starch must undergo saccharification—conversion into simple sugars--before fermentation can occur. For the Near Eastern grain-based beers, saccharification was achieved through the malting process, which causes the release of a group of enzymes called diastases which sunder the starches into simple sugars. For manioc chicha saccharification is achieved with the diastase, amylase, in human saliva. That humans have amylase in our saliva reflects our long evolutionary experience with plant starches. This saliva amylase has been deployed in brewing for thousands of years in traditional societies worldwide; it is probably the original method of saccharification of all beer starches, including the wheat and barley used by the Near East. The process is quite simple though labor intensive. The boiled manioc slices are thoroughly chewed to infuse them with amylase then spit into a large communal bowl in which the beer will be made. It is considered woman’s work. Conveniently for the Shaur men, their saliva makes for an inferior product, or so they claim.

The primary simple sugar produced by manioc starch saccharification, is the same as that produced from any starch—maltose. Wild yeasts don’t much take to maltose, but in a human environment they readily adapt to the new sugar source. Manioc was domesticated over 10,000 years ago; manioc beers were undoubtedly being made long before that. Maltose yeasts, which had adapted to maltose independently of those in the Near East and elsewhere, were available to the Shaur.

Lactic acid bacteria aren’t as particular about their sugars as yeast; Some can even work with starch, because, unlike yeasts, they can produce amylase. No evolutionary change was required of the manioc chicha LAB with respect to maltose. That’s not to say that LAB did not evolve. LAB evolved a lot, much faster than the yeast. The generation time of the brewer’s yeast--Saccharomyces cerevisiae-- is 1-2 hours under optimal conditions—and then only for brief periods. Bacteria, on the other hand, can produce multiple generations in a single minute, continuously. LAB have among the quickest generational turnover among bacteria that have been studied in the lab: 66-87 generation/minute. Therefore, LAB evolve much more rapidly than yeast, and almost unimaginably more rapidly than annual plants, like wheat (One year generation time) or domestic mammals (2-5 years).

So rapid is the evolution of LAB species in the manioc beer environment that, in the 60 years since the Shaur were forced to settle, each Shaur village has evolved unique LAB strains for their manioc beer. Not only unique LAB strains, but unique multispecies LAB ecosystems. The discerning can taste the difference in the chicha produced in villages less than 20 miles apart. Call it microbial terroir. Each village’s LAB ecosystem represents an independent multi-species domestication in the manioc beer environment.

LAB In the First Milk

The transition of LAB from plants to milk would not have been all that difficult given their ability to utilize almost any simple sugar, even newly available ones like lactose. But other bacteria with less benign effects would have also colonized the new food source. As ever, it was a competition between the fermenters and the spoilers, the good rotten versus the bad rotten. The LAB prevailed because of their competitive advantage in low oxygen environments and their ability to alter their environment through acidification, conditions in which most spoilers are doomed. Eventually, some species of LAB became so specialized on milk that they could not return to their original plant environment, in part because their genomes had become streamlined. This streamlining entailed the loss of genes that had helped them thrive in the wild but were useless in the milk environment. A genomically streamlined milk-adapted LAB would be at a disadvantage in the plant world, competing against its wild ancestors. Such genomic streamlining is a hallmark of microbe domestication.

From Sour Milk to Cheese

When left in the open, milk not only sours but fractionates into an upper layer containing most of the fats and proteins and a lower layer that has most of the lactose sugars. The upper, more solid layer is called curd; the lower, more liquid layer is called whey. By merely separating the curds from the whey, early milkers could solve much—but not all—of the lactose problem. The milk whey was probably tossed by the lactose intolerant early milkers; they focused on the largely lactose-free curds. Today the curds are made into a variety of products, including butter, cream, yogurts, and cheeses, all of which contain relatively little lactose. Cheeses contain by far the least. Today, in southern Europe, lactose intolerance remains the norm, but vast quantities of cheeses are consumed. Greek Feta contains hardly any lactose, Italian Parmigiana, virtually none.

The fist milkers would have learned to separate curds and whey early on to manufacture cheeses and yogurts. Cheeses have virtues above and beyond their lack of lactose. They retain most of the nutrients of raw milk, including vitamin D and calcium, plus additional nutrients provided through fermentation. Until the advent of Pasteurization, cheeses were safer to consume than raw milk because fermentation also eliminate potentially toxic spoilage bacteria and fungi.

Equally, if not more important is the shelf-life of cheese. For the early milkers, milk was a seasonal product, available only during the annual calving season each spring. When made into cheese, however, it could be available year-round, a true nutritional boon.

The earliest evidence for cheese-making discovered to date, comes from the Dalmatian coast of Croatia. It comes from a 7,200-year-old pottery device for seperating curds from whey. The first cheeses, though, must have been made in northwestern Anatolia, the area where intensive dairying first developed.

The microbial ecosystems required for cheeses are much more complex than those involved in sour milk or yoghurt production. LAB remain essential but yeasts and molds are also critical in the aging process, keeping the spoilers at bay, while contributing their own suits of nutrients and flavors. For each kind of cheese there is a distinctive ecosystem, and for any given type of cheese this ecosystem varies geographically.

The Rapid Expansion of Milking

This cultural innovation that was milking affected the subsequent evolution of domestic cattle, sheep and goats, as well as microbial evolution; but also the evolution of our own species. Not just our cultural evolution, but also our biological evolution—our biocultural evolution.

From Anatolia, dairy farming of cattle, sheep and goats expanded first to the Balkans (about 8,000 BP) and the Hungarian plains. From the Balkans dairy farming gradually spread to the north and west, eventually reaching Britain and northern Europe around 5,500 BP.  By the time milking had spread to central Europe, a mutation conferring lactose tolerance occurred and began to rapidly spread in the farming communities, increasing in frequency during the north-westward expansion to Britain and northern Europe, where it became nearly universal. The ability to consume whole milk must have been advantageous because of nutrients not available in fermented forms. That is, there is something in the whey; its exact nature is unknown. In part, it could simply be the water in the whey, a safe form of hydration in polluted, settled areas. Also, abundant whey proteins, which, in their powdered form are popular supplements, especially for those who prize well-muscled physiques.

Recently, it has been proposed that the most important factor present in whey but absent in the curds is the hormone IGF-1 (insulin-like growth factor 1). IGF-1, as the name implies, is an important growth factor, which may be why whole milk consumers are among the tallest populations in the world. Igf-1 influences a host of other traits as well, including age of sexual maturation in females. Those who drink milk mature earlier and produce more offspring over a lifetime, providing raw milk consuming populations a considerable demographic advantage relative to non-raw milk-drinking populations. Selection for the mutation conferring lactose tolerance in Europeans is among the strongest ever observed in a mammal. The mutation would have had no benefit had fermented milk products not acted as a scaffold.

There were two routes for the spread of farming from the Near East to Europe: one through the Balkans and central Europe, called the Danube route; the other, called the Mediterranean route, went through northern Greece and westward along the northern shore to the Iberian Peninsula. It was along the Danube route that lactose tolerance evolved; Southern Europeans remain largely lactose intolerant and consume most dairy products in fermented forms. Even in the Balkans, where the milking cultures first arrived, fermented milk products remain the norm. To the east of Anatolia, the story is a bit more complicated.

Milking Elsewhere in the Old World

European cattle belong to one of two subspecies, called taurine; in northern India, the second subspecies, zebu, was independently domesticated and soon exploited for milk. Today, India is by far the biggest milk producing country in the world. As in the Near East the first milk products were fermented due to lactose intolerance. Today though, about 75% of Northern Indian adults are lactose tolerant and can therefore consume raw milk. Since lactose tolerance there is conferred by the exact same mutation as that in Europe, it is surmised that there was an eastward migration of lactose tolerant people from the Near East, probably along the Persian Gulf where pockets of lactose tolerance occur today. As in Europe, lactose tolerance is much less common in the southern regions of the subcontinent, around 33%.

The most specialized milk-based pastoralists reside in northern and eastern Africa, a way of life that extends back 8,000 years, when foragers switched from hunting to herding, cattle, sheep and goats, and later, camels and donkeys. The Maasai and Samburu peoples are descended from these foragers in a line unbroken by plant cultivators. Cattle are the most prized. African pastoralist only eat beef when a member of the herd dies or becomes enfeebled. Instead, their diets consist mainly of milk, followed by blood. A mixture of the two is especially nutritious. Most of the milk is fermented (soured) to some degree.

African pastoralists have evolved four distinct mutations, all different from the mutation found in Europe and India, though on the same lactase-regulating part of the genome. One of these mutations is also common among Arabian Bedouins. These mutations seem to have occurred earlier than the one conferring lactose tolerance on northern Europeans. But none was as strongly selected for. As a result, many African pastoralists have more than one mutation, but some have none.

 In some cases, this is not a mystery. The Nuer and Dinka of Sudan raise cattle primarily as status symbols—and do not milk them—to be exchanged in marriage transactions. The daughters of those herders with the most cattle are most likely to marry up. Other African pastoralists may rely more on sour milk products. But some pastoralists who lack any mutation for lactose tolerance seem to be lactose tolerant nonetheless. Something else must be going on here. Recently, attention has been directed toward the microbiome.

LAB are an important component of the human gut microbiome. Perhaps some milk-consuming populations acquire particularly robust or abundant LAB gut populations, which both increase absorption of whey nutrients and mitigate the effects of undigested lactose. One way to enhance LAB in the microbiome is through the consumption of fermented milk products at an early age.

From Hunting to Herding

Plant cultivation was the foundation for agriculture, so it has long been assumed that pastoralism is derivative. But in Africa, Arabia, Mongolia and probably South America, pastoralism developed independently of plant cultivation. Moreover, in these areas of the world pastoralism probably preceded cultivation, or cultivation never developed to any appreciable extent. In principle, agro-pastoralism could involve two independent transitions by unrelated foraging peoples, one, from foraging to plant management and one from foraging to animal management.

Even in the Near East foragers may have adopted proto pastoralism as a way of life without aid from farmers, only to be integrated later into the farming economy. There is an obvious dietary advantage for cultivators who incorporated the domestic animal package—pigs, goats, sheep, cattle—into their farms, as reflected in a population boom about 8,000 years ago in the Near East, first in southeastern Anatolia, the cradle of agro-pastoralism. Elsewhere, pastoralist became increasingly differentiated from the farmers in their way of life though connected by trade.

It was long alleged that the direct transition from foraging to pastoralism would have been well-nigh impossible due to their starkly contrasting ethos. This notion is based on the view that foragers are egalitarian and food-sharing, whereas pastoralists are fiercely protective of their private property and social status. But the egalitarianism of foragers varies widely, and many pastoralists have a strong communal component. The San of south Africa provide insight into how this transition could occur.

Pastoralism came late to South Africa through migrations from East Africa and North Africa. Among those to adopt herding practices were some of the most celebrated foraging peoples, including the San, who were never tempted to cultivate. They continued to hunt but they also kept domestic goats. All wild prey was shared but domestic stock was considered private property. The same pattern is true of the Maasai, who continue to hunt at low levels. Hunting and herding are not incompatible. Far from it. Many pastoralist peoples live a life far closer to foraging peoples than do farmers. It’s not much of an exaggeration to say that many of the remaining foragers are pastoralists.  The continued existence of pastoralism, especially of the highly nomadic sort was only possible because of the transition from a primarily meat-based diet to one based on milk. Fermented milk products were an indispensable bridge. Paleos would do well to take note.