Yeast: Love and Fear, Death and Beer

By John-Manuel Andriote
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Jamal Saidi/Flickr

You might say Saccharomyces cerevisiae yeast are the house-cats of the microbial world. Although they've been domesticated at least since the Pharaohs ruled Egypt -- the earliest records show that people by then already were using the "sugar-loving" yeast to leaven bread and brew beer -- this fungus's less civilized cousins can really mess you up.

Yeast are found everywhere in the environment. The one-celled organisms -- called "yeast" from the Old English gist/gyst and Indo-European root word yes, meaning boil, foam or bubble -- don't need sunlight, do need oxygen, and are naturally drawn to sugar-rich hosts for the carbon they thrive on.

"There are people who will contend that civilization began so that humans could make beer."

Fruit and berry skins are among their favorite habitats, but the spaces between your toes, your skin, gut, genitals -- and even crude oil, which is 84 percent carbon -- suit them just fine, too. Basically if there is carbon to be had, one yeast or another will have adapted to having it.

Although some species of fungi have a single-cell yeast "phase," they aren't what we ordinarily think of as "yeast." Of the 1,500 identified species of yeast that live around, in, and on us, three in particular stand out. Foremost is S. cerevisiae. Besides its ancient and ever greater role in food, beverages, and nutritional supplements, modern biotechnology has harnessed the metabolic process of S. cerevisiae -- we know it as fermentation -to manufacture lifesaving medicines, fuel our vehicles, and even clean up oil spills.

Harmless to healthy people and present in/on all of us, Candida albicans becomes a one-celled monster when it finds a weak immune system. It's notorious for afflicting three-quarters of all women at some time in their lives with the itching, irritation, burning sensation, and soreness associated with so-generically-called yeast infections. Candidiasis, the technical name for those infections, also shows up in the form of diaper rash on a baby, jock itch, or white milky-looking thrush on the tongue.

The far more sinister Cryptococcus neoformans this year will kill hundreds of thousands of people, as it does each year. Preying on those with suppressed immunity, it's found in soil all over the world -- especially where lots of birds, particularly pigeons, leave their droppings. We all inhale C. neoformans' microscopic, airborne fungal spores, mostly with no problems. But people whose immune systems are compromised -- because they have untreated HIV infection, take immunosuppressive drugs, receive an organ transplant, or are pregnant, for example -- are at risk for developing the pneumonia-type illness cryptococcosis or, if the infection spreads to the brain, the life-threatening cryptococcal meningitis.

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Thinking past these unpleasantries, consider that 50 billion pints and 67 billion cans of beer are consumed in the United States each year, according to the Beer Institute. "He was a wise man who invented beer," said Plato.

In fact, said Jim Koch, founder and owner of the Boston Beer Company, brewers of Sam Adams, "There's some debate about which came first, beer or bread. It appears most likely it was beer."

Koch called yeast -- specifically the S. cerivisiae used in both beer and bread -- a "miracle organism." He explained, "There are people who will contend that civilization began so that humans could make beer. They figured out how to grow grain, but needed to figure out how to turn the grain into a source of nutrition and safe hydration."

The alcohol produced by yeast's fermentation -- breaking down carbon into carbon dioxide and ethanol (alcohol) -- is among the most powerful sterilizing agents available. This is why, Koch said, even the Pilgrims didn't pack the Mayflower with barrels of water that could carry all kinds of harmful organisms -- typhus, cholera, and hepatitis among them.

"Instead, they provisioned it with beer," he said, "almost a gallon a day for every man, woman, and child."

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It wasn't that the pleasure-phobic Puritans were closet lushes. "The reason was beer was a safe form of hydration," said Koch. The alcohol produced by yeast's fermentation kills every potentially harmful organism in the beer. "When God made the universe," said Koch, "he or she made nothing harmful to human beings that can grow in beer."

Gods have been invoked, thanked, and cursed since the Greeks credited Dionysus with creating wine and winemaking. But it was the Frenchman Louis Pasteur who revealed new knowledge that even the gods had never imparted. In 1857 Pasteur created the field of microbiology when he proved that alcoholic fermentation is conducted by living yeast rather than by either a chemical reaction or by magic. Viniculturists ever since have sought to capitalize on the new understanding about yeast that microbiology opened up for them.

One winemaker, noted for using "wild" yeast to make what many consider his magical zinfandels, is Joel Peterson. The owner of Sonoma, California-based Ravenswood Winery told me he prefers the indigenous yeast found on the grapes he uses because they have been used for millennia in the kind of traditional winemaking he practices. "I get more interesting characters out of the wild yeast fermentation than I do out of a monoclonal yeast fermentation," he said.

Because it takes longer -- and therefore costs more -- to let the wild yeast ferment at their natural pace, Peterson said most big commercial wineries "give an overwhelming dose of Saccharomyces" so it dominates the others, ferments faster, and is more likely to yield a predictably consistent flavor.

It wasn't coincidental that Peterson chose the less-traveled path with the less-predictable native yeast: His background as a microbiologist prepared him well. In his earlier line of work, Peterson worked closely with yeast -- though of the pathogenic sort. As a medical researcher, he studied chronic mucocutaneous candidiasis, an immune disorder in which a lack of resistance to Candida causes recurrent or persistent infections of the skin, mucous membranes, and nails, usually with Candida albicans.

Peterson said it's important to understand that each type of yeast thrives or dies according to its particular diet and environment. "The layman says 'yeast,' and that's all they get," he said. "I hope you'll make it really clear that these yeasts are very separate from one another. So Saccharomyces would never behave like Candida. It has a host and food it likes. If you put Candida albicans in grape slurry, it would die."

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In the vagina, however, Candida not only live, but can really go wild if the mix of yeast and bacteria is off-kilter.

This happens when a woman is, for example, taking antibiotics, which decrease the amount of lactobacillus bacteria in her vagina, or her estrogen level is increased during pregnancy or from taking high-dose estrogen birth control pills or hormone therapy. It can also happen when diabetes isn't controlled or the immune system is impaired by HIV or another factor. Although it's not usually transmitted sexually, it can be.

"Yeasts are colonized in about 80 percent of women."

Jill Maura Rabin, MD, professor of obstetrics and gynecology and head of urogynecology at Hofstra North Shore-LIJ School of Medicine, in Hempstead, New York, explained that the vagina's normal pH is 3.8 to 4.2. "If you keep a normal vaginal acid, it's almost impossible to grow yeast or flora in the vagina," she said.

Nevertheless, "yeasts are colonized in about 80 percent of women," said Rabin, adding,"The importance of vaginal flora in terms of general health is as a mirror of what is going on the body."

Rabin said it's wise to weigh the risks and benefits of treating a yeast infection yourself versus seeing a doctor. "By yourself, the benefit is it saves money and time," she said. "But the risk of treating yourself is you may spend money on something you didn't need, masking what's there and making it more difficult to treat."

For women who have already "been there, done that," Rabin said it's fine to treat yourself if you are confident of what you're dealing with. She elaborated in a telephone interview, "For people who know themselves well and have classic symptoms, have had [yeast infections] in the past and have no other comorbidities, I don't believe there is a risk in going to the drugstore and treating it."

On the other hand, Rabin recommends seeing a doctor if you aren't prone to yeast infections or it's not clearing up with over-the-counter treatment.

To keep Candida in check, Rabin recommends regularly taking probiotics, ideally in yogurt. "I prefer people to get their supplements in food," she said. She also suggested Luvena, a vaginal "prebiotic" that stimulates the growth of healthy lactobacillus bacteria; vaginal acid jelly that can be used three times a week right after menstruation when the pH is up; or boric acid suppositories, particularly for pregnant women.

For women prone to repeat infections -- overweight women with high-carbohydrate diets tend to have repeats -- Rabin said wearing cotton underwear is a must. "Cotton is more absorptive, but also the fibers have air space where nylon doesn't," she explained. For women who have chronic yeast infections, Rabin offers simple advice for at least partly addressing the problem: "Go commando," she said.

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You could wear a cotton mask over your face, but will still very likely inhale somewhere, at some time, the spores of Cryptococcus neoformans. Unless your immune system is severely compromised, however, you aren't likely ever to know this particular pathogen has taken up residence in your body.

Before antiretroviral therapy (ART) became available in the mid-1990s, five to ten percent of people with the advanced stage of untreated HIV infection known as AIDS were at great risk for developing the cough, fever, and shortness of breath associated with cryptococcosis in the lungs. Without the immune strength to restrain C. neoformans and its equally insidious relative Cryptococcus gattii, the fungus wreaks even greater havoc if it infects the central nervous system. Fever, headache, and a change in mental status are among the dreaded signs that cryptococcus is causing the inflammation of the brain and meninges known as cryptococcal meningitis.

Cryptococcosis is diagnosed by a microscopic exam, tissue or body fluid culture, or a rapid test performed on blood and/or cerebrospinal fluid. Treatment of an asymptomatic, mild, or moderate case involves at least six months of prescription antifungal medication, typically fluconazole or itraconazole.

An estimated 625,000 people will die from cryptococcal meningitis this year.

The Centers for Disease Control and Prevention estimate there are one million new cases of cryptococcal meningitis worldwide each year. With a mortality rate of 50 to 70 percent, an estimated 625,000 people will die from the disease -- most of them in sub-Saharan Africa, where it is one of the leading causes of death in HIV-positive people. In the U.S. today, there are only two to seven cases per 1,000 people, for a mortality rate of about 12 percent. Even if it doesn't kill you, the CDC says C. neoformans meningitis may lead to permanent neurologic damage.

"Fortunately more and more HIV-positive people are getting on treatment," said Kenneth H. Mayer, MD, medical research director at the Fenway Institute in Boston and professor of medicine at Harvard Medical School. Noting there are other populations still at risk -- including people on chemotherapy -- Mayer said that "rates of cryptococcosis in the U.S. have plummeted among people with HIV." He added, "If people with HIV start treatment and are adherent to their meds, their risks are exceedingly low."

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Yeast has dramatically reduced the risk of contracting HIV -- as well as other deadly pathogens. Once again, Saccharomyces cerevisiae is providing for humanity's health and well-being -- not only in our bakeries, breweries, and wineries, but in our laboratories as well.

Thanks to modern biotechnology, Factor 8 -- the blood-clotting protein lacking in hemophiliacs -- is produced in genetically altered S. cerivisiae. Before the early 1990s advent of recombinant synthesized factor products, Factor 8 was made from donated human plasma. In the 1980s, tens of thousands of hemophiliacs who depended on "factor" to live were infected with HIV, and died from AIDS, as a result of contaminated Factor 8 products.

Besides its other admirable and useful qualities, you might call S. cerivisiae the host with the most. It's also called the most important organism in modern biotechnology.

It was in the lab of Gerald R. Fink, a biology professor at MIT's Whitehead Institute for Biomedical Research, that a process was discovered in 1977 which allows researchers to introduce a foreign piece of DNA into yeast cells and have it expressed in subsequent generations of the yeast.

Fink described in an interview how his discoveries have led scientists not only to manufacture Factor 8 in S. cerivisiae, but also Hepatitis B vaccine, Gardisil (for HPV), and numerous other human and animal biopharmaceutical products. Because yeast, like human cells, are eukaryotic -- possessing both a nucleus, membrane-bound organelles, and mitochondria -- biotechnological techniques have made yeast the hosts of choice for human genes.

"A lot of what people are having injected into them," said Fink, "are vaccines that are human protein made in yeast by putting the gene from humans into yeast."

Half the insulin used to manage the metabolic imbalances of the world's 366 million diabetics is produced in Saccharomyces. The rest is produced in a bacteria, Escherichia coli -- better known as E. coli, the culprit behind regular outbreaks of infection from contaminated food and water that lead to vomiting and diarrhea, and can lead to kidney failure.

Fink said that in biotech applications S. cerivisiae, ordinary bread yeast, is preferable to E. coli not only because it reproduces prolifically, but because it's safe. Even after using it to produce the viral antigens used in vaccines, "you can feed it to animals," he said. Because literally thousands of pounds of yeast can be produced from a small batch, Fink added, "You can get a pretty penny for Saccharomyces" by selling the excess that isn't needed.

"This becomes a bigger issue when you are dealing with biofuels," he explained, "because, in the end, as in any industrial process, you have a problem in that you've produced so much, what do you do with the stuff?" E. coli is used to manufacture many other biotherapeutics. But after you've got what you want from it, there's the problem of having a tremendous amount of a harmful organism. This is why, said Fink, "there are processes people use E. coli for, but if you have the choice, you do it in yeast."

As scientific knowledge increases, and yeast continues to expand in usefulness and value to a variety of industries, it's clear the potential of these microorganisms is far from exhausted.

Of course not everyone is enthusiastic about all of what biotechnology has made possible, as evidenced by the ever-growing movement against so-called GMOs (genetically modified organisms) in agriculture and food.

But while debates rage over whether or not GMOs in our foods have negative consequences, a bit of perspective seems called for. Dr. Fink said that National Research Council studies haven't showed evidence of untoward effects. Pointing to the tremendous benefits of the pharmaceutical products manufactured in genetically modified yeast, he added, "Why is it not okay to eat things, but it's okay to inject them in your veins?"

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In time even bigger questions may present themselves: Has Saccharomyces, the "house cat," been domesticated to the point we can anticipate its every action and reaction, even after we've manipulated the very blueprint of its life? Is it possible the anti-GMOers will one day shout, "We told you so!" when the human genome becomes mutated in some unforeseen harmful ways because of the "cat" that got out of the bag?

For the time being, such questions are probably best debated over a frosty brew or glass of fine wine. While we're quaffing our thirst, how about raising a toast to our old friend Saccharomyces cerivisiae.

This article available online at:

http://www.theatlantic.com/health/archive/2013/05/yeast-love-and-fear-death-and-beer/275786/