Winemaking: Science or Magic?

Red wine necklace --
 (from madewithmolecules.com)

Last night I attended a networking event advertised through the San Diego Biotech Network and sponsored by PGC200.org (link).  The topic of discussion?  The Biotechnology of Enology (Oenology for you Brits).   Some days, when experiments are particularly uncooperative, I wonder what it would be like to own a winery.  Seems like a good fit since I like wine, I like science, and I like growing things.  However, I have always been intrigued by how different wines can taste even though they are made from the same grape.  There is also huge variability in different vintages from the same winery.  And unlike beer, if you let wine sit in a bottle for a few years, it can become extraordinary.   How does this happen?  I mean, how hard can it be?  Pick some grapes, stomp them with your feet, pour the shit in a vat and wait a couple years.  Seriously.  The grapes come from the same plant each year so their genetic makeup is the same.  The winemaker knows how to prepare the grapes, add the yeast, control the temperature, uses the same bins, etc.  Budweiser can make the same beer year after year… why can’t the winemakers?

Reading the abstract for the talk (biochemical pathways, genetics, chemical reactions, blah, blah, blah) I figured science must have the answers to this.  Then I saw the bit about wine tastings and immediately signed myself up.  I’ve been to a ton of scientific conferences and let me tell you, almost any mind-numbing talk can be improved with a glass or two of wine.   The speaker was Kerith Overstreet, co-founder and CSO of Bruliam Wines (link)(Bruliam sounds like something off the periodic table, but is actually a portmanteau of her children’s names).   Her talk was nothing short of fantastic.  Life-altering, in fact.   She was an MD (pathology) before switching careers to winemaking and had a sense of humor as dry as a good cabernet.  We gathered in a beautifully modern conference room and during the reception, we admired the views of the surrounding mini-mountains.  She started us off with the 2009 Hayley Pinot Noir.  It was light and pleasant (she described it as feminine).  Lucy, my partner in crime on this trip, described it as kind of bitchy.  Not sure what that means but she knows a hell of lot more about wine than I, so I just nodded knowingly.  Maybe it had too much whine.  (Thank you, thank you.  I’m here all week.) Next up was the 2009 Doctor’s Vineyard Pinot Noir.  This was from the Monterey area (Santa Lucia Highlands) and we both agreed it was really nice.  Bruliam Wines has only been operational for three years and even I can tell that these wines kick ass.  After a couple glasses of wine and some great food, we were all ready for a nap – I mean, the talk.

(The scientifically squeamish may want to sit down now.  Or skip ahead a few paragraphs.)

Kerith started us off gently, talking about how the root stocks were different from the vines and that the two are actually selected independently, like picking out a top and a bottom.  Then she went into fermentation like a bat out of biochemical hell.  Early on, it’s all about the glucose pathway.  The added yeast converts sugars to ethanol and the genetic composition of the yeast determines the speed and efficiency of the process.    Alcohol is toxic to yeast, so there is a beautiful biochemical feedback loop at this stage.  As the yeast becomes stressed, pathways are activated (and are up-regulated by the dropping sugar concentrations) that release fatty acids, sterols, and other chemoprotectants (let’s call this ‘the good stuff’).  During the fermentation process, oxygen is bad – unless you are trying to make vinegar -- however, there is always a little bit in there and so some of ‘the good stuff’ gets oxidized to make “magical stuff” (ie, tannins).  These are my scientific terms, not Kerith’s.  You know when a girl gives you that “come hither” look?  That’s the female equivalent of a tannin.

Pretty simple so far, right?  Just control the reaction and you get your wine.  Not quite.  After the yeast is done, you then have to add bacteria for the second fermentation.   This step stabilizes the wine by converting nasty biochemical byproducts to more storage-friendly chemicals.  In the case of red wine, this is also where the magic occurs.  As the sugar level is crashing and the yeast are starting to die, you sprinkle bacteria ‘like fairy dust’ into the fermenting goo.  Choice of strain is again critically important (homofermenters, heterofermenters, malolactic strains, zzzzz) but whatever you add activates different biochemical pathways which, in turn, gives you different levels of “good stuff” and “magical stuff”.  Timing and balance is everything.   You can’t let the yeast or the bacteria over-process the biochemical byproducts or you wind up with wine that is “all alcohol and no sex”.   I’m calling these chemicals “magic” because honestly, people don’t know what most of these chemicals are or why they are important.  But they are mission-critical for body, flavor, mouthfeel, and aging, particularly in red wine.  These magic tannins are the key to turning a good bottle of cab into a mind-blowing experience.  How does that work?

Catechin - one of the magic molecules

One wine characteristic I know well is the dry, leathery feel of a cabernet.  It makes your mouth feel weird and some really young cabs are like drinking liquid desert.  The a-ha moment in Kerith’s talk came at the end when she was talking about aging.  When a cab is young, there are a lot of tannins in there and the taste can be very harsh.  That sensation in your mouth is because tannins bind very strongly with proteins in spit, so they cling to the sides of your mouth.  One of the magic tannins is from the flavin-3-ol subgroup  of flavinoids (not to be confused with the famous rapper) and is commonly known as catechin.  Catechin is a small chemical (see picture) but when it gets oxidized, it can form a dimer.  Dimers can be oxidized to form trimers, and so on.  As the chemical polymerizes, it has a harder time binding to the proteins in spit.  So as the wine ages, it seems “softer” or more mellow.  Other phenols and flavinoids can also be oxidized and combine to form very exotic chemicals that cause changes in the character of the flavor (more chocolate, less berry, hint of woodsmoke, etc).  I can’t even begin to comprehend how many different combinations of chemicals you could create inside that bottle.  You might be wondering how this happens -- I said that oxidation was bad (vinegar) and oxygen levels are low during fermentation.  Where does this tiny bit of oxygen come from?  The cork.  The OTR (oxygen transmission rate) of the cork results in micro—oxygenation of the wine.  These magic tannins are basically buffering the wine from a slow oxygen leak, protecting it from the bad types of oxidation that lead to enological disaster and creating tasty flavinoids in the process.  The more tannins in the wine, the longer it can be stored and potentially the better it gets.  Wine is truly an amazing witches’ brew! 

  So, is winemaking driven by science or magic?  If it’s science, is sure isn’t governed by classical mechanics.  There is little to no predictive power and the system is far too complex to control.  Even comparing it to quantum mechanics is a stretch.  Every batch that is set up will come out different because at the end, the distribution of tannins (type and concentration) cannot be predicted.  It will taste generally like a cabernet, but the specific taste will be different from batch to batch and sometimes even bottle to bottle.   Since there are multiple biochemical pathways involved, each with interdependent feedback loops, and the final output is so exquisitely dependent on the initial conditions, I wonder if the process is actually chaotic.  What if winemaking was described by something like a Lorenz attractor?  These non-linear dynamical systems are characterized by being globally deterministic (it tastes like a cab) but locally unpredictable (I taste bell peppers!).  The weather is a good example as is the stock market.  This means that good winemaking will likely come from empirical observations, intuition, and a little luck.  I do wonder if someday scientists will understand which tannins correspond to what taste or sensation.  One could then make synthetic wines using a simplistic fermentation process followed by the addition of supplemental tannins to create the right body.  But somehow, I don’t think that scientists will ever be able to, um, convincingly fake it.

The final bottle of the night was a 2009 Rockpile Rocky Ridge Zinfandel – “a zin for cab lovers”.  The description said it was “the perfect yin-yang of dark berries and savory spices” with “spectacular structure, layered complexity, and balance”.  Blah, blah… whatever.  This stuff was orgasmic. I really didn’t care what the hell was in there.   If that’s what a really good Zinfandel tastes like, I might be a believer.  So I poured myself another glass, let it open up a bit, and chalked one up for magic.

Zombie science!

In addition to my day job as a scientist, I am also an aspiring writer of Young Adult fiction.  I like the concept of the teenage biohacker, because there is so much fertile ground to work with.  Science fair projects that go horribly wrong or the biology teacher who has an odd obsession with road kill.  In my first novel, a group of teens create primitive life in their basement lab.  The protagonist’s mom is a scientist studying extremophilic bacteria, and he learns from her that it is pretty easy to make long chains of amino acids (ie, proteins) using a temperature cycler.  When he tries to do this himself, disaster strikes and they force the system to evolve into an organized, self-replicating structure with life-like characteristics.  A prominent scientist learns about their discovery and steals it for his secret research on zombies. 

Sound crazy?  Check out the new book by Dr. Steven Schlozman called The Zombie Autopsies.  CNN interviewed the Harvard/Mass Gen psychiatrist about the book (see link) and I think it should be essential reading for any high school AP Biology class.  He uses a very scientific framework to discuss the pathogenesis of the disease, the mathematical models that predict how fast it could spread, and, of course, offensive and defensive strategies for our survival.  (Spoiler alert: The odds are pretty good for the zombies.) 

So, what is his take for the root cause?  Interestingly, he uses infectious proteins called prions as a source.   A paper published in 1982 by Stanley Prusiner first described these infectious proteins, and at the time it violated many dogmas of molecular biology (he won the Nobel Prize in 1997 for this work).  Prions are the culprit behind Creutzfeldt-Jakob disease, fatal insomnia (how awful!), Gerstmann-Straussler-Scheinker (GSS) disease, bovine spongiform encephalopathy (the technical term for Mad Cow disease), and probably other diseases and conditions that have not been linked yet.  Infectious prions are simply misfolded proteins that get into the brain and result in amyloids (aka ginormous blobs) that destroy brain tissue.  But they aren’t just any ginormous blob, they actually have a pretty well-defined structure and are quite stable.  The current thinking is that the infectious prion serves as a template that allows normal prion proteins in the brain to structurally convert to the infectious form.  However, even today the exact mechanism remains controversial.   What is known, however, is that as the infection spreads the brain disintegrates.  In CJD, this results in the slow death of the patient but in Schlozman’s book, it results in a zombie.  He makes a compelling case that if a different prion variant were to evolve such that the brain gets chewed down to the core, the patient would remain alive but would no longer be capable of cognitive thought.  All that would be left is basic brain function, an unquenchable hunger, and a dysfunctional fight-or-flight response (a “drunk crocodile” was Schlozman’s description). 

So does this mean that future college biology majors will be using Schlozman’s book for courses in Zombie Biology?  Maybe.  Although prions make for a compelling zombie disease, there are also other pathogens that have been suggested to turn your awkward, hormone-crazed, teenage neighbor into a clumsy, teenage zombie.  (Trust me, there’s a difference.)  In many zombie apocalypse movies, a virus causes people to wig-out and, just like rabies, is transmitted to hapless store clerks (and other minor characters) through a bite or a scratch.  This is also a very real possibility, since there are many brain-damaging viruses in circulation.  A few mutations in one of these guys and the brain buffet is open for business.  There are some scientists who also speculate that prion diseases are initially triggered by viruses. 

Then there is Toxoplasma gondii.  T. gondii is a parasitic protozoa whose primary host is the cat but requires a rat host as part of the full lifecycle.  Rats have a natural aversion to cats and are hard-wired to avoid areas with evidence of feline activity.  So how in the world does T. gondii manage to thrive?  Yup. Zombies.  When rats are infected with T. gondii, the infection affects brain function.  Instead of aversion, there is strong scientific evidence that rats become attracted to cats and lose their sense of risk aversion (for example, see Berdoy et al, “Fatal attraction in rats infected with Toxoplasma gondii.” Proc. Biol. Sci, Vol 267 pp1591-4, 2000).  If they could write, these zombie rats would carry little signs that say “Eat me… nom, nom, nom”.  Human infection by T. gondii usually has mild, flu-like symptoms but in some cases, it can produce symptoms very similar to schizophrenia (for a recent review, see Henriquez, et al., 2009 “Neuropsychiatric disease and Toxoplasma gondii infection.” Neuroimmunomodulation, Vol 16, pp122-133).  Crazy, unihibited humans?  Only a small step from zombies... or college freshmen.

Anyhow, this is a great example of some really cool, but offbeat, science. Yeah, this is on the fringe and is half-entertainment and half-science, but in reality, zombies are not only plausible, but something we may actually have to contend with someday.  A  prion-like protein that my protagonist discovered may be one of the catalysts.  Will he and his friends find a way to stop the zombie apocalypse?  Will his girlfriend become the first victim… or the first zombie!?  Let’s just hope she doesn’t own a cat.

In the beginning...

Welcome, welcome.  Please step forward and don’t be shy.  I’m sure you are all thinking to yourself What in the world is Dwyer doing in the lab now??  But I assure you, you are completely safe.  The purpose of The Dark Lab is not to have you make zombie rats or some other exotic creature, although you may encounter the stranger, darker side of science.  I like efforts that do not stick close to the shore of the NIH/NSF grant funding lake  but, rather, research that swims out to the deeper, darker parts.  Research that takes risks.  People don’t get beheaded for this stuff anymore (ahhh, the days…) but it is still rare to see work that really pushes the limits, chokes the Dogma, or shifts paradigms out of their comfortable little beds.  Why should anyone else care about this stuff?  Because there has never been a better time to be involved.  A new Golden Era of science has come where one doesn’t need a PhD and a fancy lab to make major contributions.  Hackerspaces have popped up across the country, giving interested people access to basic DNA technologies.  High school students are working on the protein folding problem, discovering galaxies, and mining data from the human genome project for new ways to attack cancer and other deadly diseases.  Access to information on the internet has never been easier, computational power has never been stronger, and there is a growing interest from scientists to use volunteers from the lay community to help them with their work.  The opportunities are limitless!    I have worked in the pharmaceutical industry for many years and I know first-hand that a good idea can come from anywhere!  So, if something you read about here seems pretty cool… get involved!  Just watch the floor as you leave the lab… one of my zombie rats has chewed through the steel cage again.