Unit 12. Alcohol

Script 34. Allergy to wine.

The oenophile's lament

An explanation for a most unfortunate condition.

One of life's sadder statistics is that about 8% of people get sneezy and stuffy-headed after drinking wine. This mild allergic reaction is often blamed on preservative chemicals called sulphites, but they are responsible for only an eighth of cases. The reason for the rest is obscure. Giuseppe Palmisano of the University of Southern Denmark, however, thinks he knows the answer.

As he and his colleagues report in the Journal of Proteome Research, the culprits are glycoproteins - compounds composed, as their name suggests, of sugar and protein. That is not a complete surprise. Glycoproteins are implicated in several other allergies. But Dr Palmisano thinks he has identified the ones specific to wine.

To do so he started with a cheeky little chardonnay, treated it with ice-cold trichloroacetic acid and ethanol to precipitate any glycoproteins, then digested those glycoproteins into smaller molecules called peptides that can be analysed by mass spectroscopy. He screened the results against a database of known allergenic proteins. Three stood out. One is similar to allergenic proteins found in latex and pears. Another looks like a second latex protein and an olive protein, both known allergens. The third resembles one of the most rampant allergens of them all, a ragweed protein that causes hay fever.

Whether winemakers will be able to act on this knowledge is moot. But it might be possible to tweak the production process to reduce the presence of the allergens. In any case, you can now blame that stuffy feeling that comes after drinking on glycoproteins, not alcohol. Honest. (From The Economist, November 27, 2010)

Script 35. Brewing.

Heady discoveries

The yeast that gave rise to lager is tracked down to South America.

In the 15th century a schism opened in the world of beer. Brewers in Bavaria alighted on a new version of that age-old drink - one that liked to be fermented in the cold and could thus be brewed in winter. The lager revolution had begun.

The difference between lagers and more traditional ales lies in the yeast. Ales are made with baker's yeast, Saccharomyces cerevisiae. Lagers use a hybrid, half cerevisiae and half something else. The interloper, though, has never been found - until now.

After a worldwide search, a team of geneticists has pinned it down to South America. Chris Todd Hittinger of the University of Wisconsin-Madison and Diego Libkind of the Argentine National Council for Scientific and Technical Research, found their quarry over 11,000 km (7,000 miles) from Bavaria, in the cool alpine forests of Patagonia. As they explain in a paper in the Proceedings of the National Academy of Sciences, the newly described species, named Saccharomyces eubayanus, lives in galls that infect beech trees there. These sugary galls often ferment on the forest floor, and locals have been known to make an alcoholic beverage from them. Genetic sequencing confirmed that the yeast in the galls is 99.5% identical with the non-ale half of the lager-yeast genome.

That solves one mystery but creates another. Human transport is the only way the fungus could have travelled from Patagonia to Europe, but exploration of the New World did not begin until the end of the 15th century, and Patagonia was not reached until the 16th. Yet there are records of cold-fermented beer being made in Munich as early as 1420.

Dr Hittinger suspects lagering in its basic form - lengthy and cool fermentation - did precede the arrival of eubayanus, but that these early lagers were poor. Then, in one batch, eubayanus drifted in and could thrive at the low temperatures which cerevisiae disliked. Brewers favoured that batch, and the yeast spread. Indeed, the historical record provides a hint that something was afoot around this time. In 1553 Bavaria outlawed summer-made beer because wintertime brews had outstripped them in quality.

Eventually, the two yeast strains hybridised to form Saccharomyces pastorianus, the yeast used by lager brewers today. Those brewers will cheer the discovery of eubayanus, as it opens a trove of genes that did not make the transition to pastorianus but which might help the process of cold brewing. One South American beer company is already discussing using pure eubayanus, as well as lab-created hybrids, in a test brew. Whether that will improve the lager's flavour is another matter. As Dr Hittinger points out, natural selection has done a pretty tasty job already. (From The Economist, August 27, 2011)

Script 36. Combating addiction

Can a vaccine stop drug abuse?

It may be possible to vaccinate people against addictive drugs.

The idea of vaccinating drug addicts against their affliction is an intriguing one. In principle, it should not be too hard. The immune system works, in part, by making antibodies that are specific to particular sorts of hostile molecule. Such antibodies recognise and attach themselves to these molecules, rendering them harmless. Vaccines work by presenting the immune system with novel targets, so that it can learn to react to them if it comes across them again.

The problem is that the molecules antibodies recognise and react to are the big ones, such as proteins, that are characteristic of bacteria, viruses and other infectious agents. Small molecules, such as drugs, go unnoticed. But not for much longer, if Kim Janda of the Scripps Research Institute in San Diego has his way. In a paper just published in the Joumal of the American Chemical Society, Dr Janda and his colleagues suggest how a vaccine against methamphetamine, a popular street drug, might be made. If their method works, it would open the possibility of vaccinating people against other drugs, too.

The idea of a methamphetamine vaccine is not new. The problem is getting the immune system to pay attention to a molecule that is such a small target. The way that has been tried in the past is to build the vaccine from several components.

First, there is a large carrier protein that forms a platform for the target. Then there is the target itself, a set of smaller molecules called haptens that are attached to the carrier. These may either be the drug in question or some analogue of it that, for one reason or another, is reckoned to have a better chance of training the immune system. Finally, there is a chemical cocktail called an adjuvant that helps get the immune system to pay attention to the carrier protein and the haptens.

Dr Janda noticed that past experiments on methamphetamine vaccines had all revolved around tweaking either the carrier protein or the adjuvant, rather than tinkering with the haptens. He thought he might be able to change that, on the basis of work he had carried out previously, trying to design a vaccine against nicotine. In particular, nicotine is a highly flexible molecule. That makes it hard for the immune system to recognise. To overcome this, his team on the nicotine project had to work out how to fix their haptens to the carrier protein in a way that rendered them less capable of twisting and turning, and thus made them easier for the immune system to identify.

In the new study, Dr Janda and his colleagues report that they have performed a similar trick with methamphetamine haptens. They used computer models to visualise the haptens in three dimensions and thus work out how the molecules could be rearranged such that they could not spring, twist or turn when being examined by the immune system. In light of this information they designed six new methamphetamine-like haptens. Once built, they attached the new hapten molecules to carrier proteins, mixed them with adjuvant, injected the results into mice and waited. After several weeks they tested the mice to see if the animals' blood contained antibodies to methamphetamine.

Of the six new haptens, three successfully provoked the mice to make such antibodies. As a bonus, one of those three also stimulated the production of antibodies against another widely used drug, amphetamine. That is still a long way from providing a working vaccine, but it is an important step forward. And if human immune systems react in the same way to the new vaccines as murine ones do, the day when a drug addict might be offered vaccination rather than opprobrium will have come a little closer. (From The Economist, May 21, 2011)

Script 37. Oral health

Wine gums

One of the components of red wine protects against tooth decay.

Without regular brushing and flossing, teeth accumulate bacterial films that secrete acid and cause cavities. But sometimes even these good habits are insufficient to shift such films, and a chemical called chlorhexidine has to be deployed as well, in the form of a mouthwash. Chlorhexidine, however, stains teeth and affects people’s sense of taste, so an alternative would be welcome. And Victoria Moreno-Arribas of the Institute of Food Science Research in Madrid believes she may have one: a derivative of red wine.

Dr Moreno-Arribas knew from previous work that red wine has antimicrobial properties, but she could find few studies which looked at whether it attacks dental biofilms specifically. To rectify that, she and her colleagues grew five troublesome oral bacteria, Actinomyces oris, Fusobacterium nucleatum, Streptococcus mutans, Streptococcus oralis and Veillonella dispar, on discs of hydroxyapatite, the main component of dental enamel. They fed the bugs by dipping the discs into solutions of sugar mixed with saliva collected from volunteers, who spent several hours spitting into jars. The results have just been published in the Journal of Agricultural and Food Chemistry.

As expected, the bacteria grew to form films on the discs, just as they do on teeth. After a week of such growth the researchers exposed each disc to one of five treatments every day for a further seven days. Some were swished around in red wine (a pinot noir, vintage 2010) for two minutes. Some were swished in a de-alcoholised version of this wine. Some were swished in chlorhexidine, some in a 12% solution of ethanol (ie, of the same alcoholic strength as the wine) and some in plain water. This combination of experiments let Dr Moreno-Arribas determine whether wine has antibiofilm properties beyond those bestowed by its alcohol content, and also how well it compares with chlorhexidine.

Sadly for oenophiles, chlorhexidine still came out on top. But wine did well against two of the five species, F. nucleatum and S. oralis. Intriguingly, in the case of S. oralis the de-alcoholised version was even more effective than the full-strength stuff.

To find out which chemicals within the wine were having the desired effect, Dr Moreno-Arribas and her team added wine extracts such as flavanols and yeast polysaccharides to the mix and repeated their experiments. The magic turned out to be provided by a group of chemicals called flavan-3-ols.

Regrettably, this work does not suggest that a nightly glass of wine is a sensible substitute for a thorough dental brushing before you go to bed. But it might, if pursued, allow an alternative to chlorhexidine mouthwash to be developed—perhaps one that does not have such a horrible effect on taste buds (From The Economist, May 31, 2014)