February 17, 2012 | 4
This article is the third (see the first and second articles here) in a miniseries of six articles (yes, I added one) that will be posted over six days about civilization, fungus, and alcohol. The first four articles are already determined, but just how this series finishes up will be chosen by the comments and ideas of readers.
One Gin for me, One for the Cholera–A life can be unpredictable. It can begin one place and end another, or begin one place and end up in the same place but with a very different point of view. Janet Guthrie was working as a scientist in her hometown of Inverness, keeping an eye on water quality. It was a good job. She was happy, but maybe a little restless. Restlessness has killed people. Restlessness will send you off to war. Restlessness sent Janet Guthrie to graduate school. She decided to get a masters degree from the Department of Microbiology at the University of Aberdeen, while continuing to work during the day. She would have to continue to work full time, but would make time. Then things changed. She started reading about health around the world but also in her place, where she walked around every day, the place she knew, Inverness, Scotland. Inverness is a peaceable city, at least now, a city known for its spirits. It was not always. Beneath the stonework and busy streets lurk ghosts.
[Image 1: Inverness, Scotland in the early 1900s. Ghosts not apparent in photo, though present.]
In the early 1800s, Ivnerness suffered an outbreak of cholera. Cholera is a terrible and brutish disease caused by a bacteria species, Vibrio cholerae, which ensconces itself in the gut where it causes ferocious diarrhea and vomiting (which help it to find other hosts) and, often, death. It can now be easily treated, but in many places it is still not. Last year three to five million people contracted cholera and more than a hundred thousand of those individuals died. Historically cholera would have been even more common for the simple reason that it is transmitted from one person to another when people drink water or eat food contaminated with feces and for most of our civilized history, such was, and in many places remains, our tendency.
Cholera appears to have evolved in India and then spread around the world, traveling from one contaminated source of water to the next. In August of 1832, people began to get very sick in Inverness, Scotland. They did not know the story of cholera. They just knew they were sick. They convulsed with unstoppable diarrhea and vomiting. The disease went house to house. Its spread lasted roughly eleven weeks and when it was over more than a hundred and seventy people had died. The town hall and meeting rooms had to be turned into makeshift hospitals. As Guthrie read through the stories of the deaths, she was struck by the randomness of what had happened. For example, on May 11th, 1832 it was reported that at “Fort George, a soldier died of cholera & a female has recovered from it.” Why him, why not her? Surely there was some reason1a.
Guthrie found herself attached to the stories of the people who had been affected. She began to wonder whether there was something different about those who survived. The deaths seemed so random. Then she found the second piece of the puzzle, the one that made her want to see all of the others. She found a poster from the time of the cholera outbreak, urging people to avoid uncooked fruits and vegetables AND to drink fermented and spirituous liquors, at least in moderation. The sign was simple. It did not come with an explanation of why this was might be a good idea. At the time, no one yet understood what cholera was, much less how it contracted. But Guthrie was interested in the poster. She found herself wondering, often, whether that advice was actually useful. Could drinking alcohol actually save your life?
Guthrie became consumed with this question. As an article in her local newspaper, the Inverness Courier, put it, she was spending much of her time “experimenting with red wine, gin, carrots, apples and plums.” Her thesis would explore whether clean vegetables or strong drinks could save someone from cholera, even when the world around them seemed to be falling apart. Guthrie planned to compare the survival of Vibrio cholerae in gin and red wine (as well as apples and plums). Her approach would test whether cholera in a drink would be killed and perhaps, and this is my speculation, also provide some indication of what might happen to cholera in your mouth or gut once the alcohol was consumed. If flies could kill their parasites with booze, maybe humans could too.
[Image 2: A rare view of a solitary cholera pathogen, Vibrio cholerae. In real life, it seldom arrives alone.]
There are at least two ways drinking might save you from cholera. Drinking alcohol might actually kill pathogens in the human gut or bloodstream, much the way alcohol in the bloodstream of fruit flies kills their parasites. Guthrie did not test this possibility, though I will return to it. The other scenario is one in which if all the liquid you consume is in boiled soups or spirits, you might not be exposed to cholera in the first place. While fermentation itself is likely to kill most pathogens, many alcoholic drinks, including the gin made in Inverness in the 1800s have water added to them after they are produced. Similarly, many ships of explorers carried beer diluted with water (such that essentially all they drank was beer water). In the case of Inverness, the water would have come from the contaminated river. Would the alcohol be enough to kill it?
Guthrie wanted to know. She took flasks in which she had added cholera to water. She then added Dry London Gin diluted to different concentrations and, separately, a range of different concentrations of ethanol. The question was whether the gin or ethanol would kill the pathogen and whether there was a minimum concentration necessary to do the trick. Guthrie stirred her drinks and waited.
Actually, she stirred her drinks, waited, and then repeated the experiment, again and again. After several months of late hours, after work, everything was completed and she could look at her results. Cholera is a tough beast. It is conceivable it would survive the alcohol and, if it did, it would mean those individuals who followed the health department’s urgings might actually have been at more risk.
As she did her research, stepping back a little every so often for perspective, Guthrie found she was not the only one to consider the influence of alcohol on pathogens. Others had stumbled on similar obsessions, though her focus was gin and theirs was nearly always wine. Some of those studies were completed when she began her work. Others were just getting underway. The wine studies tested whether a good glass of red could affect the presence of pathogens in drinks. They tested whether it affected those same pathogens in mouths. In one case, the studies even tested whether or not wine could kill pathogens in a simulated gut. Another tested whether those who drink wine tend to have fewer of some pathogens, such as the bacterium that causes ulcers, Helicobacter pylori. Guthrie read about these studies (whose results I will also shortly reveal), but she wanted to know about her quarry, gin.
Guthrie’s results were simple, a single diagram which barely needed explanation. When water was added to cholera, the cholera lived on, unaffected. When alcohol with a high concentration was added, the cholera died quickly. The alcohol killed cholera, much as it kills wasps the wasps that prey upon the innards of flies. The results for the cholera (and humans) are less detailed than those for the flies (It is nearly always true we know more about the health of flies than of humans.). Yet, the results were clear. All of the concentrations of alcohol she tested killed cholera. The higher the concentration of alcohol, the more quickly the cholera died. Notably, the time it required for gin to kill pathogens was anywhere one to twenty six hours depending on its concentration, not immediately. If someone drinks your gin and, in doing so, leaves for you a pathogen of some sort or another, your gin could still be contagious. In other words, if you see someone in the active throws of cholera, you can give him your gin, just don’t ask for it back.
Keeping the Ship Healthy–Guthrie’s study was a starting point, but, particularly in the context of the large number of other studies published in the last years and months, it begins to tell a story of cholera and alcohol and perhaps part of the story of alcohol and disease more generally. Alcohol (and presumably, although Guthrie did not test it, fermentation) can kill cholera. Guthrie showed this effect can occur in water and would likely have occurred in the drinks of patrons in the early 1800s in Inverness. It seems possible individuals who drank alcohol during the cholera outbreak may have been less likely to die of cholera. Elsewhere, a study of wine and cholera in France in the 1900s found those individuals who consumed wine tended to be more likely to be spared, maybe, Guthrie believes, the same happened in Inverness. Nor is that the end of the story. Other studies have also shown that tequila that is 10% alcohol can kill salmonella, shigella and E. coli (all implicated in Montezuma’s revenge as well as other maladies). Ten percent ethanol, on the other hand, was less effect against the same pathogens and, separately, against cholera, suggesting alcohol either needs to be combined with the specific (magical) compounds in wine or tequila that result from fermentation or in high concentrations. The picture is still incomplete, but emerging. Through the babble of dozens of new studies, one sees concrete hints of what might be.
What happens when this alcohol, which can kill microbes in flasks and petri dishes enters the body? Personally, my guess would have been that once alcohol enters the body, its effects on microbes are done. It is diluted and otherwise sloshed about in the stomach and then has the large surface area of the gut over which its potentially small effects might be spread. Fortunately, I wasn’t the one asked if it was worth studying the effects of alcohol inside the body. In the last five years, studies have now shown, in fits starts and breakthroughs big impacts of alcohol on bacteria in our bodies.
Drink Away Cancer?—Individuals who drink wine or beer regularly but modestly or that have done so throughout their lives are at a reduced risk of the ulcer and gastric-cancer causing bacteria Helicobacter pylori (The effect was much more pronounced for wine than beer, sorry to say). The most recent study of the effects of alcohol on H. pylori was not an experiment and yet, in as much as it accounted for as many variables as seems conceivable and considered nearly ten thousand subjects, is very suggestive. H. pylori has also been shown to be killed in the lab by wine, across several different studies. A glass a day may indeed keep an ulcer away2.
If you Have a Model’s Stomach—Another study, this one employing a model stomach found that when you gave the stomach wine, the wine was capable of killing cells of the pathogen Listeria innocua, a bacteria psecies in the same genus as the pathogen associated a form of food poisoning called Listeriosis, which kills two out of ten people it infects. In the model stomach, wine also slowed the growth of Listeria populations. And so if you have a model’s stomach, your wine might help to defend you against Listeria bacteria. No steps appear to have yet been taken to test this in actual stomachs or to compare the odds individuals who do and don’t drink wine contract Listeriosis. Next steps exist, and I suspect will be taken. Mysteries also exist. Like many studies of the benefits of wine in pathogen control, this one found wine to have an effect greater than that of ethanol of the same concentration, though just why remains a bit magical3.
Libation to the Chicken’s Ancestors—In our kitchens, we pour wine into glasses, but we also pour it on food, whether because it tastes good or as libation to the chicken, who could surely, at that point, use a sip. Marinating in wine, it turns out, has benefits though beyond libation and taste. Wine is able to kill species of Campylobacter quickly, in liquid, with none of the bacteria measurable after 15 minutes. The effect of wine on Campylobacter within the meat itself is less complete, but still enough to provide some benefit. Not that anyone is marinating steaks with grape juice, but the study found grape juice did not have the same effect. Something again seems to exist in the magic of fermented grapes. We will come back to that magic in tomorrow’s story4. On its own, this study says nothing about what is going on inside our bodies, but if wine affects the food on our plates, it may also affect it in our mouth and in our stomachs.
[Image 4. Pouring libation to the ancestors. Alcohol is not only consumed nearly everywhere today, it is often done so with a great deal of ritual, reverence perhaps for its power to give health and also to take it away.]
A drinker’s mouth—A growing literature now shows drinking wine or beer can influence the microbe species in your mouth. New studies show both wine and beer (as well as coffee) tend to lead to mouths with fewer species of microbes. This shift is clear. Less clear is whether a lower diversity is good or bad5. However, other studies find at least some of the bad news plague-forming bacteria in human mouths do become more rare when individuals drink wine.
Mice Should Not Drink—So far, few studies have actually experimentally considered the effects of wine on live animals. One clear exception is a study on mice in which it was discovered that mice who drink wine do not appear to stand a reduced risk of bacterial infections. They do, however, especially when they have had lots of wine, look really silly6.
The study of drinking in mice, jokes aside, indicates more studies in actual animals (instead of flasks and petri dishes) are necessary. Surely, one could find volunteers for an experimental study on the benefits of drinking, though I suppose it is the dose of cholera it is hard to convince people to take. Yet, it seems more and more clear, a little nightly drink may help keep you healthy when it comes to bacterial pathogens. Washing your hands also helps and, for the millions of people still at risk of cholera, clean drinking water is what is really needed. In the modern context, clean water beats alcohol as a cure for nearly every disease alcohol might remedy. For one, alcohol fails to save children, who are the most susceptible to many bacterial pathogens, including those that cause diarrhea and kill many millions each year. For another, while Alcohol can kill cholera, E. coli and more, heavy drinkers are unlikely to experience these benefit. If individuals drink very heavily, the acid content of the stomach is reduced and, separately, their immune systems become compromised. Together, the reduced acidity of the stomach and reduced potency of the immune system actually appear to increase the odds that heavy drinkers contract cholera. Heavy drinking also, of course, brings with it many other health problems. If you die of drink, you can’t be saved from cholera or anything else. But the big question is not how these drinks affect us today, but instead about how they shaped our early story and, in doing so, the rise or fall of nearly every subsequent society.
Did We Domesticate Wheat and Barley to Make Beer to Save Ourselves from Disease?—In the first article in this series, I discussed the hypothesis that wheat and barley and perhaps other crops were first domesticated to produce alcohol rather than for bread or other daily foods. One reason for the early desire for alcohol might have been to prevent disease. What we know about the history of disease suggests early settlements may have prospered (or failed) as a function of whether or not they could ward off disease. The new studies I’ve discussed here suggest alcohol may indeed help to prevent several of the sorts of diseases most likely to have threatened early settlements7.
If wine, beer, gin and other alcohols are good for pathogen prevention, their influence on the trajectory of history may have been great and varied, including but not exclusive to an effect on the origins of agriculture8. Maybe the ages of exploration would not have happened without beer, wine and other drinks. Water on ships tended to become contaminated with pathogens. Beer and wine, on the other hand, remained “pure.” Perhaps those cultures that succeeded in exploration did so through the aid of alcohol. Columbus’s ship was, by some measures, half beer. Even the pilgrims made their way west one drink to the next. They landed at Plymouth Rock not because of its beauty but instead because that is where they ran out of beer. Wine and beer can bring benefits. They may have saved our early societies and helped us to explore the world. Some night, they might save you from a pathogen, but, it is worth remembering, they might also kill you. Those aboard ships knew wine and beer kept them healthy, even if they did not know why. Henry the VII made sure his ships carried more beer than food and even then it was sometimes was not enough. During the Spanish Expedition, John Stile wrote to the king, ”And it please your Grace, the greatest lack of victuals here is of beer, for your subjects had [lyver] for to drink beer than wine or cider, for the hot wines dothe burn them and the cider dothe cast them in disease and sickness” The cider lacked alcohol. The beer had it, perhaps in enough quantities to kill at least some of what ailed those aboard. At least the sailors, and maybe our early agricultural ancestors, appear to have consumed alcohol, in part, to ward off disease. In other words, humans may be as clever as flies, at least when it comes to self-medicating with alcohol.
[Image 5: Henry VIII, whose ship the Mary Rose provides a good measure of just how much alcohol tended to be onboard ships, be they war ships or ships of exploration. It is estimated that on the King's ships, each ship was supplied with enough beer that each man could drink a gallon a day, which would have accounted for all of his liquid consumption.]
But what about the question of whether the origin of agriculture owes its debt to the demand for alcohol, not for bread or some other food? All of the evidence so far points to the possibility that alcohol, in those early villages may really have saved lives and so may really have been in demand for its benefits. But there is more to this story. Another possible explanation for the early link between alcohol and civilization exists, a possibility that gives less credit to those humans and more to the fungus. To explain, I need to turn to the termites and other insect societies who in their dark tunnels acted out a story very similar to our own story a hundred million years before.
Table of evolutionary contents: Here you can skip ahead or backward to the other chapters in the story of the other species in our daily lives, whether they bethe cow, the chicken, the hamster, bacteria (on Lady Gaga, on feet, in bathrooms,as influenced by antimicrobial wipes, as probiotics, in the appendix), pigeons and urban gardens, house sparrows (to be published next week, stay tuned), predators,diseases, dust mites, basement dwellers, lice, field mice, viruses, yeast, the fungus that produces penicillin, bedbugs, houseflies, or something more.
Or for the big picture of how Rob thinks these stories come together to make us who and who we are, check out The Wild Life of Our Bodies. Rob Dunn is a writer and evolutionary biologist in the Department of Biology at North Carolina State University. Find him on twitter at robrdunn. Find him in person somewhere in Europe with his family while they are all on sabbatical.
1-Caveat: It can also kill you.
1a-Guthrie, J.S. and D. O. Ho-Yen. 2011. Alcohol and cholera J R Soc Med. 104:98; doi:10.1258/jrsm.2011.110013 and Guthrie, J.S. H. McKenzie and D. O. Ho-Yen. 2007. Alcohol and its influence on the survival of Vibrio cholerae. British Journal of Biomedical Sciences. 64: 1-2.
2-A big caveat exists here. The reason the researchers were investigating a link between H. pylori and alcohol is because gastric cancers seem to be among the few cancers that are less likely as a function. Many cancers seem to increase in their incidence. And so, a glass a day might make gastric cancer less likely, but in essence what one is doing is trading one form of cancer for another, at least probabilistically. For the original study, see…Gao L, Weck MN, Stegmaier C, Rothenbacher D, Brenner H. 2010. Alcohol Consumption, Serum Gamma-Glutamyltransferase, and Helicobacter Pylori Infection in a Population-Based Study Among 9733 Older Adults. Ann Epidemiol 2010; 20(2): 122-128
3-You were dying to know. Here is the description of the model stomach. It sounds less sexy when you hear the details… “… a stomach model was developed having as base chemical factors the pH value, the volume of the gastric juice and the time of permanence of the food in the stomach. Commercially available sterile homogeneous chicken baby meals (Blédina) were used as food matrix. The gastric juice was simulated by adjusting the pH to 2 with HCl (1 M). The proportion of 400 mL of acid solution to 300 g of solid meal was used (Malagelada, 1977). One-thirty milliliters of simulated gastric juice was added to 100g of food. The eVect of the gastric protease pepsin was evaluated. A digestion time of 2 h was assumed.” The description is not easily digested, I know. From the study… Fernández et al., 2007. The antimicrobial effect of wine on Listeria innocua in a model stomach system. Food Control, 18: 1477–1483
4-I had several chicken jokes inserted here earlier, but my friends and family counseled against them. Isohanni P, Alter T, Saris P. Lyhs U. 2010. Wines as possible meat marinade ingredients possess antimicrobial potential against Campylobacter. Poultry Science. 89: 2704-2710.
5-C. Signoretto, F. Bianchi, G. Burlacchini, F. Sivieri, D. Spratt, and P. Canepari, “Drinking habits are associated with changes in the dental plaque microbial community,” Journal of Clinical Microbiology, vol. 48, no. 2, pp. 347–356, 2010.
6-It should not be surprising the effects of drinking alcohol, be it beer, wine, gin or something else, differ among animals, as a function of which pathogen is studied and do to many other factors. What one must remember is the magical part of the story of alcohol and pathogens is that the world is microbial. To quote another one of my recent blog posts where I made this point…
”This is a good moment to point out what is obvious to microbiologists but not to the advertising agencies who tell us to kill the germs, namely that it is not possible to kill “the germs.” The world is dense with other species. Every inch of every thing around you right now is covered in living cells, cells that make do with what you leave them. Your only choice in terms of how you affect these other species, this universal, shimmering, majority, is a choice of which of them to favor and which to disfavor. Microbes happen (link to story).”
As a consequence, each sip of wine is affecting not a single pathogen but instead hundreds of species, most of them hangers on with no effect or even beneficial microbes.. Our ability to predict the precise consequences of those changes is part good luck and part voodoo. We can show that wine has an effect or that beer does, but showing how those effects ramify in our bodies, from one species to the next is a long way away. For the mouse study, see…Sugita-Konishi, Y.; Hara-Kudo, Y.; Iwamoto, T.; Kondo, K. Wine has activity against entero-pathogenic bacteria in vitro but not in vivo. Biosci., Biotechnol., Biochem. 2001, 65, 954−957.
7-Perhaps it is for this same reason that drinking wine in many cultures tends to be said to “aid digestion,” in as much as it might prevent pathogen associated diarrhea. Such an idea is old. The Greeks used to drink diluted wine as the main beverage because it was good for the health, long before it was understood pathogens were bad for the health.
8-Here a quote from a great paper by Weiss, M. E. B. Eberly and D. A. Person is worth reprinting in full, as evidence of the long cultural association between drinking wine and disease prevention and, also, the strangeness of the world… “In 1721 [four condemned criminals were recruited to bury the dead during a terrible plague in Marseilles. The gravediggers proved to be immune to the disease. Their secret was a concoction they drank consisting of macerated garlic in wine, which immediately became famous as vinaigre des quatre voleurs (four thieves' vinegar).] It is still available in France today. This anecdote has been used to emphasise the health benefits of garlic, although the wine probably protected them as much as the garlic did.” From 1995. Wine as a digestive aid: comparative antimicrobial effects of bismuth salicylate and red and white wine. BMJ 311: 23-30.
Image credits: (from old UK photos, http://www.oldukphotos.com/inverness-shire-inverness.htm), Tom Kirn, Ron Taylor, Louisa Howard – Dartmouth Electron Microscope Facility,Berger Collection: id #69 (Denver, Colorado), Julie Strand.