Pros and Cons: Alcohol Consumption for 10M Years
We’ve been imbibing alcohol for ten million years, and the start of that long drinking binge coincided with our descent from the trees. So alcohol may have brought us (along with lots of hangovers), some measure of our humanity.
Certainly, it now seems to have played a role in our continued humanity, according to Santa Fe evolutionary biologist Matthew Carrigan. For Carrigan offered, in a recent Proceedings of the National Academy of Science, evidence that our hominid ancestors developed a genetic mutation for metabolizing the ethanol found in fallen rotten fruit just as climate change was thinning trees, and hominids were leaving them.
“Our study suggests the connection between ethanol and humans is much deeper than thought,” Carrigan told Bioscience Technology. “One of the most important transitions in human evolution was our adaptation to life on the ground. Our study suggests the ability to process ethanol without suffering [too toxic] inebriation/intoxication was an important part of this transition.”
The debate
When humans started partaking of forbidden fruit has long been debated. Some think our ancestors started imbibing as the first fruit fell 80 million years ago. Others argue we started tippling 9,000 years back, when we began processing food.
Carrigan decided to settle the debate by examining the genetic evolution of the enzyme alcohol dehydrogenase 4 (ADH4), which degrades alcohol. Starting with genetic sequences from 28 different mammals, he used maximum-likelihood analysis to calculate changes in the gene’s sequence going back 70 million years.
From this he created nine synthetic versions of the gene in its varied ancient forms, and transferred them into E. coli. These produced proteins he tested on ethanol.
Most of the ADH4 enzymes failed to metabolize ethanol. But the “10 million-year-old” enzyme, hailing from the period when forests gave way to grasslands, and hominids diverged from orangutans—and leapt out of the trees—there was a “striking” shift, the report said. One mutation let ADH4 metabolize ethanol 40 times more efficiently.
“I remember clearly the day I first tested the ancestral enzymes and observed the dramatic change resulting from the mutation in our ancestor 10 million years ago,” Carrigan told Bioscience Technology. “I had been doing most of this work late at night and on weekends” because some thought he was “wasting” his time, as ADH4 was considered a retinol metabolizer. Finding little retinol in plants, he guessed ethanol may be the target of the ADH4 lining our digestive tracts.
But this was not conventional wisdom, so he conducted experiments after-hours “in a lab little bigger than a closet. It was so small it would overheat from the equipment if I didn't use a fan to circulate cool air from the hallway. The first time I ran the trials of the ancient enzymes, I was so surprised by the dramatic shift I repeated the experiment twice to be sure I didn’t make a mistake. I was so excited by the results, but there was no one there to share the news with...so I texted my co-worker Oleg the good news.”
Why do the study in the first place? “Evolutionary biologists study so many peculiar and fascinating examples of organisms adapting to their environment, there is a cliché in our field: 'Life will find a way,'" he said.
“When I began this research, I thought, ‘If ethanol is present in naturally fermenting fruit, why wouldn’t some frugivores adapt the molecular machinery to process it?’" Still, Carrigan was surprised his experiment led him back 10 million years. As fruit was a big part of our diets for 40+ million years, “I expected an adaptation to metabolize ethanol would have occurred much earlier in our evolutionary history than 10 million years ago.”
But it made sense “once I began to consider the ecological changes occurring near when ADH4 changed so dramatically. I realized this change may be part of a larger story about adapting to a semi-terrestrial life. Fruit will ferment while still attached to the tree, so it is certainly possible arboreal organisms will consume ethanol. But the appearance of an enzyme optimized to metabolize fermented fruit near the time fossils indicate this ancestor began adapting to a semi-terrestrial life (where fermented fruit is more likely) suggests this organism was consuming fermented fruit. Fermented fruit is generally not as desirable as non-fermented fruit because of the toxic by-products of metabolizing ethanol, so I suspect fermented fruit was a second choice, exploited when preferred food (unfermented fruit) was not available.”
The winning ADH4 version apparently arose in a shared ancestor of humans, chimps, and gorillas.
More to the story
Patrick McGovern says there may be even more to the story. Head of the Biomolecular Archaeology Laboratory of the University of Pennsylvania Museum of Archaeology and Anthropology, McGovern has advanced, in two books, the theory that we may have imbibed even earlier—with even more profound ramifications.
Carrigan’s work “presents important new corroborating evidence for the ‘Palaeolithic Hypothesis,’ which posits that early hominids were probably already making wines, beers, meads, and mixed fermented beverages from wild fruits, chewed grains and roots, honey, and all manner of herbs and spices culled from their environments in the Palaeolithic period, which comprises some 99 percent of our largely unknown history,” McGovern told Bioscience Technology. One of his books even argues “fermented beverages were likely humankind’s first biotechnology.”
He continued: “Further research is needed to elucidate the other related ADH enzymes, which comprise approximately 10 percent of the human liver that convert alcohol to energy, and ALDH (aldehyde dehydrogenase), which clears the body of a much more dangerous compound. Ancient human experimentation in making alcoholic beverages was probably also spurred on by our sensory awareness of alcohol, and the plethora of aromatic compounds produced by fermentation, and most importantly, the pleasure cascade of neurotransmitters unleashed by alcohol in our brains.”
McGovern said that later, "Fermented beverages clearly eased the difficulties of everyday life (for example, the workers who built the pyramids of ancient Egypt and Mesoamerica were paid in beer), lubricated the social fabric by bringing human groups together, contributed to a joyful exhilaration in being alive, and even extended life because of its anti-oxidant properties and the fact that botanicals with medicinal benefits can be more easily dissolved in an alcoholic medium than in water. Such biological and anthropological concerns need to be addressed in future research. Indeed, fermentation is probably the first energy system on earth, and the physiology for consuming and processing alcohol, as well as the genes for inebriation (for example, barfly, cheapdate and happy hour in the fruit fly) are shared with humans and many other animals.”
The future
Carrigan said ethanol may have “played a role in fostering creativity, facilitating social bonding, or relieving psychological stress,” if his work does “not yet support that…It is logical humans would have discovered fermentation accidentally even earlier than the Palaeolithic period.” But it is less likely to him that early hominids, at least, deliberately fermented fruit, as drunkenness would be dangerous in the wild. Given the “dramatic change” seen “in the ancestor we share with gorillas and chimpanzees, and because the appearance of this mutation coincides with climate-induced adaptation to a new habitat, we think this change is most likely an adaptation to enable exploitation of a new food source, fermented fruit. Because this fermented fruit is of inferior quality, the enzymatic change in our ancestors most likely occurred in a context of nutritional stress when preferred food was less abundant.”
As his study suggests, gorillas and chimpanzees may still eat fermented fruit, and he hopes to study them to see if, when, and why they do it in the wild. He will also seek other ethanol-metabolizing enzymes.
