Survival Arts

WILT: taking cancer seriously enough to really cure it

Eight weeks ago, I hosted Dr. Aubrey de Grey for his second talk at Google in Mountain View, California, a follow-up to his earlier Google talk in the SENS series, "WILT: taking cancer seriously enough to really cure it":

ABSTRACT

The intrinsic genetic instability of cancer cells makes age-related cancers harder to ... all » postpone or treat than any other aspect of aging. Any therapy that a cancer can resist by activating or inactivating specific genes is unlikely to succeed long-term, because pre-existing cancer cells with the necessary gene expression pattern will withstand the therapy and proliferate. WILT (Whole-body Interdiction of Lengthening of Telomeres) seeks to pre-empt this problem by deleting from as many of our cells as possible the genes needed for telomere elongation. Cancers lacking these genes can never reach a life-threatening stage by altering gene expression, only by acquiring new genes, which is far more unlikely. Continuously-renewing tissues can be maintained by periodic reseeding with telomere elongation-incompetent stem cells that have had their telomeres lengthened in vitro with exogenous telomerase. I will describe why WILT may become a uniquely comprehensive anti-cancer modality, and the practicalities of performing it and avoiding side-effects.

Everything You Wanted To Know About Stem Cells... But Were Afraid To Ask

Some weeks back, my (now) friend Dr. Daniel Kraft, a physician scientist at Stanford, came to Google at my invitation to give a talk, "Everything You Wanted To Know About Stem Cells... But Were Afraid To Ask":

ABSTRACT

Stem cell technology and the debate surrounding it has generated a great deal of excitement ... all » and controversy in recent years. The field is surrounded by misconceptions, hype and yet very significant potential. In this talk we'll cover: defining what are stem cells really and where do they come from... the differences between embryonic stem cells and 'adult stem cells' (i.e. derived from our own bone marrow, fat, umbilical cord blood, placentas and even our kids teeth) and emerging technologies to utilize these cells in powerful and novel ways. We'll cover current clinical uses of stem cells, ongoing clinical trials in regenerative medicine (i.e. using marrow derived cells to treat heart attacks, vascular disease, stroke and even diabetes), upcoming trials utilizing embryonic stem cells, and some of the likely near term and future applications as well as challenges remaining in order for this field to reach its full potential.

Aubrey de Grey: "Prospects for extending healthy life - a lot"

Aubrey de Grey gave a Tech Talk at Google's Mountain View campus this week, and I was privileged to attend. I've seen him give a longer, earlier version of this presentation before - at Stanford in June 2005 - and was impressed more than ever. Enjoy:

ABSTRACT

It may seem premature to be discussing approaches to the effective elimination of human ... all » aging as a cause of death at a time when essentially no progress has yet been made in even postponing it. However, two aspects of human aging combine to undermine this assessment. The first is that aging is happening to us throughout our lives but only results in appreciable functional decline after four or more decades of life: this shows that we can postpone the functional decline caused by aging arbitrarily well without knowing how to prevent aging completely, but instead by increasingly thorough molecular and cellular repair. The second is that the typical rate of refinement of dramatic technological breakthroughs is rather reliable (so long as public enthusiasm for them is abundant) and is fast enough to change such technologies (be they in medicine, transport, or computing) almost beyond recognition within a natural human lifespan. In this talk I will explain, first, why (presuming adequate funding for the initial preclinical work) therapies that can add 30 healthy years to the remaining lifespan of healthy 55-year-olds may arrive within the next few decades, and, second, why those who benefit from those therapies will very probably continue to benefit from progressively improved therapies indefinitely and thus avoid debilitation or death from age-related causes at any age.

Telomolecular Nanotechnologies

What a day! Just as I'm getting ready to attend Aubrey de Grey's talk at Google, I find out that a martial arts training buddy of mine, Dr. Pete Lohstroh, recently left his research position at UC Davis to take a senior scientist position at Telomolecular Nanotechnologies, specializing in the application of nanocircles to telomere extension therapy (one of several approaches they're taking). Congratulations Pete!

Nanoparticles Delivery of 'Suicide DNA' Kills Prostate Tumors

Nanoparticles Delivery of 'Suicide DNA' Kills Prostate Tumors

"...using nanoparticles developed by members of the Alliance for Nanotechnology in Cancer, a team of investigators at the Lankenau Institute for Medical Research, in Philadelphia, has developed a DNA-based therapeutic agent that has the potential to treat both enlarged prostates and localized prostate tumors. When tested in mice, this new agent specifically targeted prostate tissue, producing no toxic effects in surrounding tissues..."

Quote of the Day (from a private mailing list I run, with permission)

Frank Bieser writes:
> Perry E. Metzger wrote:
>> Without enough people working on the problem, we won't finish in
>> time. Right now, I'd say smart people are the biggest missing resource.
>
> And why might that be? Where did all the smart people go?

They didn't "go" anywhere. They've never been in the field.

How many smart people were working on orbital rocketry in 1920? A half
dozen, perhaps. Lots of people claimed the whole idea was bunk, too,
including the New York Times. Later on, lots of people joined up.

Today, not many people are working on Drexler's vision. That doesn't
mean it isn't worthwhile -- it just means that the field is young and
lots of people are still skeptical about it. I suspect that the number
of people actively working on it numbers less than 20, and possibly
less than 10.

There is enough work for thousands of people to push on this for many
years to come. At some point, we'll get IA or AI and the pace will be
able to pick up, but that point still seems pretty distant. Meanwhile,
direct molecular manipulation and molecular manufacturing pose a very
hard set of problems -- possibly the hardest engineering problem yet
faced by mankind -- and we need more minds to make progress. On the
flip side, MNT will also bring the biggest revolution in civilization
yet experienced, dwarfing everything that came before, so I see it as
a worthwhile problem to attack.

Still, we lack enough smart people working on it. As any good VC can
tell you, money is something of a commodity, but smart people are
rare. More smart people are needed.

Perry

Me at my most Poindextrous...

I'm going through a year's worth of iPhoto archives and found this, taken in organic chemistry lab by my friend Jenny... me in Maximum Nerd mode:

Dendrimers to improve chemotherapeutic delivery

An interesting blog article about the use of dendrimers in targetted drug delivery systems, sent me by Tom Burroughes in London.

University of Michigan scientists have created the nanotechnology equivalent of a Trojan horse to smuggle a powerful chemotherapeutic drug inside tumor cells – increasing the drug's cancer-killing activity and reducing its toxic side effects.

Previous studies in cell cultures have suggested that attaching anticancer drugs to nanoparticles for targeted delivery to tumor cells could increase the therapeutic response. Now, U-M scientists have shown that this nanotechnology-based treatment is effective in living animals.

pKa of the N-H proton on LDA

I needed to look this up for study so, given how difficult it was to find this value, I'm mentioning it for future Googlers:

According to "Chemistry of Amines," in section 4, "Important Reagent Bases", the pKa of the N-H proton on the conjugate acid of lithium diisopropylamide (LDA) is 35.7.

"Rapid Gene Synthesizer Will Enable Custom Microbe Construction"

Thanks to Perry for bringing this to my attention: "Rapid Gene Synthesizer Will Enable Custom Microbe Construction."

My first DNA electrophoresis

I am really, really enjoying my biology class, a concentrated term of cell & molecular biology. Students in this program spend about four times as much time in lab, learning industrially useful techniques, as do students in comparable programs in the University of California system. In the last three weeks, I've had hands-on time doing protein electrophoresis, conjugation (bacterial DNA transfer), and DNA electrophoresis. Here's an image of our team's first DNA gel:

The DNA is from purified coliphage Lambda virus, 48,502 Kb (kilobases) in length. Lane 1 is pure, uncut DNA. Lane 2 is DNA restricted (cut) by Eco RI enzyme, Lane 3 restricted by Hind III, and Lane 4 by both (the restriction sites are different, resulting in more, smaller DNA fragments.)

Lanes 5 through 7 are subsamples taken from 2 through 4, subjected slowly and thoroughly to the action of the enzyme DNA ligase, resulting in outrageously long, randomly recombinant strands.

The gel is purified agarose treated with ethidium bromide. The image above is a high-contrast Polaroid of the gel UV-transilluminated to fluoresce in the visible spectrum (reddish orange, here shown in black and white).

This stuff is outrageously fun.

Quote of the Day

In science, 'fact' can only mean 'confirmed to such a degree that it would be perverse to withhold provisional assent.' I suppose that apples might start to rise tomorrow, but the possibility does not merit equal time in physics classrooms.

Stephen Jay Gould

Keep the fricken' lacrymators under the hood!

I seemed to have been the only person this morning other than my instructor to have paid attention to the warning on the bottle of crotyl chloride, "Danger: lacrymating agent!"

It was also amazing to see the number of people dispensing silver nitrate without gloves... low toxicity risk, but high chance of Rorschach tattoos on one's hands (hint: silver nitrate is photosensitive.)

"Immunotherapy Halts Alzheimer's in Mice"

Perry Metzger reports in "Immunotherapy Halts Alzheimer's in Mice" that:

...the injection of antibodies targeting the beta amyloid plaques into the brains of mice with a close analog of Alzheimer's disease managed to trigger a response in which the immune system cleared the plaques. Neurofibrillary tangles associated with the disease cleared spontaneously shortly after the amyloid plaques vanished.

Francis Crick has died

Perry Metzger reports that Francis Crick has died. He will be missed.

"Diminished Capacity": Perry Metzger has a blog now

My old friend Perry Metzger gave in today and finally started a blog. Now to convince him to add a comment mechanism...

"New Technique for Imaging May Improve Study of Proteins"

Courtesy of Perry Metzger today: "New Technique for Imaging May Improve Study of Proteins" and its related story direct from IBM, "IBM Scientists Make Breakthrough in Nanoscale Imaging."

IBM scientists have achieved a breakthrough in nanoscale magnetic resonance imaging (MRI) by directly detecting the faint magnetic signal from a single electron buried inside a solid sample.

Quote of the Day

A biophysicist talks physics to the biologists and biology to the physicists, but when he meets another biophysicist, they just discuss women.

Unknown

Name Reactions, by Jie Jack Li

A big thanks to James and Steph for their gift of the Springer title Name Reactions by Jie Jack Li, a compact atlas of 331 reactions in organic chemistry, from "Abnormal Claisen rearrangement" to "Zenin benzine rearrangement." This should be truly useful from the fall term onwards; thanks guys!

Bizarre Science

Recommended by Monica White: the blog "Bizarre Science."

Quote of the Day

Now, I am no climate scientist, but I harbor a suspicion that maybe, just maybe, one factor impacting on the Earth's climate just might be - now, I'm just throwing this out - the sun. I find discussion of the sun's impact on global weather to be oddly absent from the reams of paper speculating on how minute variations in various gases here on earth may affect climate, rather like speculating on how adjusting the air pressure in your tires a few ounces might affect fuel efficiency without ever considering the, well, fuel you are putting in the tank.

Robert Clayton Dean

BATF forcing rocket amateurs out of the field

This is nasty and upsetting news from Steve Pegram: "Rocket Hobbyists Dropping Hobby" due to hamfisted, jackbooted regulation by the goons of the BATF. Just when we're seeing the spirit of innovation in rocketry and space travel rekindled, the government is working to snuff that spirit. This crap needs to be fought... which seems to be happening by default, since many rocket hobbyists have chosen to ignore F-Troop anyway.

Quote of the Day

Organic chemistry is the chemistry of carbon compounds. Biochemistry is the study of carbon compounds that crawl.

Mike Adams

Quote of the Day

When the war finally came to an end, I was at a loss as to what to do... I took stock of my qualifications. A not-very-good degree, redeemed somewhat by my achievements at the Admiralty. A knowledge of certain restricted parts of magnetism and hydrodynamics, neither of them subjects for which I felt the least bit of enthusiasm. No published papers at all... Only gradually did I realize that this lack of qualification could be an advantage. By the time most scientists have reached age thirty they are trapped by their own expertise. They have invested so much effort in one particular field that it is often extremely difficult, at that time in their careers, to make a radical change. I, on the other hand, knew nothing, except for a basic training in somewhat old-fashioned physics and mathematics and an ability to turn my hand to new things... Since I essentially knew nothing, I had an almost completely free choice...

Francis Crick
What Mad Pursuit, Basic Books, New York, 1988, pp 15-16.

Hinomoto Molecular Modelling Kits

In chemistry lecture, and studying outside class, I often use a molecular modelling kit made by Darling Models to help me visualize the stereochemistry of various molecules. I like my kit, but it's rather bulky, so I don't always have it immediately at hand. A few days ago, one of my classmates showed me the kit she carried, which is very much more compact and does most of what we need to know (in respect of linear and branched hydrocarbons and some of their halogenated derivatives): a Student Organic Chemistry C-set from Hinomoto Plastics. The Hinomoto kit fits in a small pocket pouch, and is very solidly constructed. Some of the components look amusingly like dice from the game Dungeons & Dragons, by the way.

Ralph Merkle's "Nanotechnology and Medicine"

Here's an interesting short article by Ralph Merkle written when he was working for Zyvex (before he moved on to Georgia Tech): "Nanotechnology and Medicine".

Quote of the Day

[A bit of context: this quote refers to an amusing incident where a religious cultist in a forum I frequent blew up when he was called out on an issue of "quantum mysticism" he couldn't support. - Russell]

I think [a particular theist twit] actually did good job of defining by example an important concept in quantum mechanics: the uncertainty principle.

He obviously has some beliefs, and we could either know the position or the energy of his beliefs, but not both.

He chose to show us the energy.

Dan McCoy

Iron. You wanted to know about iron?

I found a pretty cool resource on iron, one of my favorite funky transition metals.

Some more respirocyte information

Another source of concise information on the respirocyte concept.

Lecture: "The Artificial Synapse Chip: Towards an Electronic Prosthetic Retina"

My thanks to my longtime friend (I avoid the term "old friend" for such a young woman) Kennita Watson for alerting me to this lecture at Stanford on 23 June 2004: "The Artificial Synapse Chip: Towards an Electronic Prosthetic Retina" by Harvey A. Fishman, M.D., Ph.D, Stanford University School of Medicine, the Director of Ophthalmic Tissue Engineering and Chief Ophthalmology Resident in the department of Ophthalmology.

Age-related macular degeneration (AMD) is the most common form of severe and irreversible blindness in the U.S. Our research program consists of a highly interdisciplinary effort between physicians, engineers, and scientists to develop a neural interface that will connect the output from a digital camera to individual retinal cells in patients with AMD, thus bypassing injured cells.

By the way, this sounds like a skillset for the type of research physician I find really interesting:

Dr. Fishman's area of expertise is translational research that uses a multidisciplinary approach to develop novel therapies for blinding diseases in the eye – in particular, Age-Related Macular Degeneration. His research bridges the gaps between tissue engineering, surface science, nanofabrication, chemistry, neuroscience and retinal transplantation biology in Ophthalmology. His background in new technologies and medical science is diverse including bioMEMS, chip-based microfluidics and confocal and time-lapse microscopy, neuroscience/nerve cell regeneration and macular diseases in Ophthalmology. He has made contributions in the fields of microfluidics, laser-induced fluorescence detection, separation science, and biosensors.

Quote of the Day

I imagine respirocytes as minuscule objects consisting of roughly 18 billion atoms arranged in small balls about a thousandth of a millimeter in diameter. Each respirocyte is a tiny pressurized gas tank equipped with small pumps. Respirocytes are nanobots that move with the blood. In the body's periphery, they release oxygen and absorb carbon dioxide. In the lungs, they do the opposite, recharging themselves with oxygen. The exchange of gases is regulated by minute sensors. Though the respirocytes are modeled on red blood corpuscles, they transport oxygen two hundred times more efficiently than the natural item. A small syringe-full of respirocytes could carry as much oxygen as your entire bloodstream.

Robert A. Freitas Jr
28 July 2000

Having a wonderful time, wish you were here

I crashed late last night, and woke early this morning, and am ready to do it all again today: the Foresight SAG continues.

Structural molecular orbital diagrams: some tools and a method

The advice below can easily be applied to many different academic endeavors, including use in non-science classes. Here's a recipe. First, buy these pens:

• The Bic brite liner, of course. Avoid excessive markup with this. Really. Some of you may need to be told this, so here goes: what good is text that is mostly highlighted?
  
• The classic Bic "4-color pen": you can't survive without this!
  
• At least one Sharpie pen (keep one in your labcoat pocket) for marking test tubes and centrifuge vessels. I know, these have nothing to do with the method below, but a good lab geek always has one in her pocket anyway.
  
• A set of colored pencils. I use the erasable Sanford Col-Erase, but non-erasable Crayola colored pencils are cheaper and color adequately too.
  

The classic Bic 4-color pen should be in any student's pocket anyway. Annotating your own notes is so much easier when you use different colors. Here's an application to chemistry: you can draw much more easily understandable molecular orbital "balloon diagrams" (using the 90% probability surface standard or other representation of choice) if you assign colors to orbitals and stick with those colors.

The "balloon diagram method" I use:

Before placing any of these pens to paper, first visualize where on that paper you'll place your molecule's constituent atoms, bearing in mind that you'll usually be converting a flattened Lewis dot diagram to a projection of some angle of a 3-dimensional structure. I strongly recommend therefore that you do the full Lewis diagram first, taking into account resonance, where applicable.

Draw the central atoms first, e.g. the backbone carbons in most organic structures, then place the peripheral atoms next, populating with hydrogens as the very last step (since they're invariably peripheral).

Using the medium-point 4-color pen, draw circles in your color of choice for those species (almost always only hydrogen) whose atomic orbitals do not hybridize. In other words, the 1s orbital around the hydrogens.

Assuming you're not working with d-block elements - that is, you're dealing only with s-block and d-block elements but not funky transition metals - move to the central atoms and, referring to your Lewis dot diagram, ask yourself about the hybridization of the atom's atomic orbitals, e.g. sp, sp2, sp3. Draw the outlines of the orbitals using a different lobe color for each hybridization type.

Using a closely matching color for each orbital type (to match your pen color outlines), lightly shade your orbitals with a the side edge of a colored pencil. Your structural orbital diagram should be very clear by this time. If you've done this step right, you should have axial bonding overlaps between neighboring 1s (unhybridized) and sp, sp2, or sp3 orbital lobes.

At this point, again consult your Lewis dot diagram and identify any pi bonds. There's more than one way of representing the electron cloud manually. Don't try to reproduce the printed textbook "pi sandwich" style of orbital: you don't have the tools at hand. Instead, I recommend picking yet another color and schematically representing, by overlay, the pi bond by drawing a line from the tip of one unhybridized p-orbital to its atomic neighbor, making sure to indicate the signs of the wavefunction of each p-orbital lobe (hint: bonding orbitals match in signs; pick an arbitrary sign and make sure it's matched with its neighbor). Do the same for the opposing lobes. Label all pi bonds as such.

Your instructor may have a different standard for handwritten orbitals. Consult first.

Draw short, black lines across (perpendicular to) the sigma bonds, labelling sigma bonds as such. Revisit all the atoms and, again using another color, write the hybridization type near the atom. Here's an important step many students forget: indicate resonance in whatever manner your instructor will accept, again in another color, in a manner that clearly indicates electron delocalization. Label the line (what I use) as "resonance".

Hope someone finds this useful... this started as a rant on colored pens and mutated into a set of recommendations on drawing molecular structural orbital diagrams.

Linus Pauling Research Notebooks

This is pretty cool: scans of Linus Pauling's Research Notebooks taken from 1922 to 1994 (he lived 1901-1994).

As with many scientists, Linus Pauling utilized bound notebooks to keep track of the details of his research as it unfolded. A testament to the remarkable length and diversity of Dr. Pauling's career, the Pauling Papers holdings include forty-six research notebooks spanning the years of 1922 to 1994 and covering any number of the scientific fields in which Dr. Pauling involved himself. In this regard, the notebooks contain many of Pauling's laboratory calculations and experimental data, as well as scientific conclusions, ideas for further research and numerous autobiographical musings.

A couple of excellent chemistry textbooks

On Friday during his office hours, my chem prof was deeply surprised to find that I didn't yet own a copy of Zumdahl's "Chemistry", which is not our school's official text... so he gave me one of his, a new copy, the Instructor's Annotated Edition (5th)! He had an extra, so it became mine... a good, good man, and deeply flattering.

A couple of people in a chemistry forum I frequent had recommended Linus Pauling's "General Chemistry". I saw a copy in my local Border's - the 1989 Dover reprint of the 3rd edition (the last, 1971) - and flipped through it. I was impressed, so I took note of its ISBN. The shelf price was $20, but I found a pristine copy on Amazon Marketplace for half that price and ordered it. Can't wait to get it.

A caveat, by the way - and this is no hit on the book, given its age - if you're going to study coordination compounds of metals, you'll need to supplement your reading with Zumdahl, or another modern source. Although Pauling mentions the work of Alfred Werner in a sidebar of a couple of pages on the matter, he (quite understandably) doesn't mention crystal field theory & d-shell splitting (of course he wouldn't). Very highly recommended.

I don't like having to say "I told you so"

...especially when it involves bad things happening perilously close to me.

There's a phenomenon well known in its universality among martial artists, pilots, and laboratory investigators (and many others, though these are categories to which I can personally claim memberhip): beginners can be dangerous!

For fledgling pilots, safety comes first in collision avoidance and minimal aptitude in takeoff and landing (especially landing). Student pilots at this point truly have to be watched carefully.

For martial artists, dealing with beginners means being aware that the beginner is often not aware of how easy it is to hurt your training partner, and hence how important it is to learn how to train properly so that you don't get hurt "when it's your turn to lose" in practice. Genuinely dangerous!

Today, I had a reminder of how easily late-first-year chemistry students can be genuinely dangerous too. I'm a stickler for thorough preparation for lab investigation, which includes adequately understanding any reaction schema involved in the labwork. Today's labwork involved the generation of noticable volumes of chlorine and nitrogen dioxide gasses, the latter of which was to be generated by heating of reagents including concentrated nitric acid under a fume hood.

Well, today a couple of giggly Chinese girls (otherwise sharp but who are treating chemistry as a checklist item, a waypoint on the way to medical school) who didn't fully understand the reaction schema, were heating the nitric acid solutions at their bench! Before any of us had time to react, they'd already generated a visible cloud of white, toxic smoke. The hell of it was, they simply stood rooted where they were standing, looking embarassed. They were not embarassed that they stood a risk of death or injury, but that they'd been caught not having prepped their lab notebooks with the proper procedure! A couple of other students managed to shake them from their (not yet literal) mortification and pull them away from the danger, while my instructor and I started hitting the buttons on the emergency fume hood evacuation systems, hoping we could clear the cloud quickly and safely by drawing it across the room into the hood system (and upwards from there into the Great Dilution of the atmosphere... note that our lab building is gratifyingly free of pigeon poop for a very good reason.)

Later, I did what the instructor later noted was probably more effective and shocking coming from a fellow student rather than from him: I dressed down the girls in front of everyone else, telling them they must come into the lab prepared next time, rather than faking their way through an experiment. Funny thing was, just a few minutes before the incident I'd commented to my instructor that many of my classmates didn't seem to have any grasp of the difference between real laboratory science and ritual magic.

Oh, and several minutes later I witnessed another girl come up to the instructor asking if the open centrifuge tubes she was holding - which were continuously generating chlorine gas as a side reaction - were hazardous! Argh!

At least our labwork on Thursday of last week went without incident. You see, there was a reaction on that day which required careful control of pH in one of the test solutions containing thiocyanate ions (SCN-). We needed to maintain a particular weakly acidic environment in order to favor a certain desired product. You see, a more acidic pH would have tilted the reaction strongly to the production of HCN, hydrogen cyanide gas...

It's these little moments that help move things along

It's 4 weeks into my fourth quarter of general chemistry, and I'm deep into a weeks-long laboratory assignment involving identification of unknown cations in mystery solutions... a forensics exercise involving minute amounts of reagent, fiddly and frustrating, but necessary. It'a also a transition to the full-blown organic chemistry sequence, which I'm eagerly anticipating.

In the midst of my frustration, my chemistry professor, whose labtime desk sits next to my workbench, handed me my previous quarter's graded final exam, the taking of which marked the completion of the most difficult course in the general chemistry sequence.

I made a perfect score on that exam.

I feel really, really good right now. Really good. I've been given permission to copy that exam before I return it to my professor... and it's going right into the folder of recommendations and other papers I can show to schools and employers in the near future. Woohoo!

Foresight Senior Associates Gathering 14-16 May 2004, Palo Alto CA

I'll be attending all 3 days of the 14-16 May 2004 Foresight Senior Associates Gathering in Palo Alto, California. I very highly recommend this event to anyone interested in molecular nanotechnology. If you're not intimately familiar with nanotechnology, but want to learn, I enthusiastically recommend the 8-hour "Fundamentals of Nanotechnology" tutorial session on Friday: I'll be attending myself to dust off and deepen my own understanding.

K. Eric Drexler's personal nanotechnology website up

Mark Miller informs me via Orkut that K. Eric Drexler now has a personal nanotechnology website, e-drexler.com.

On the inadequacy of some historical chemical terminology

I was helping one of my chemistry classmates study after class this morning. Our topic of conversation was electrochemistry. My classmate's confusion was over the terminology used in voltaic cells, e.g. oxidation, reduction, cathode, anode, cation, anion, etc. It occurred to me in the course of discussion that her confusion was due to the use of the term "reduction", which simply means "a reduction in oxidation state by electron donation"; it's a useful numerical indication of that state, not of the physical configuration of the element being "reduced". I'd long ago internalized the actual meaning, so it had slipped me that to a very bright but non-native speaker of English, "reduction" would seem to indicate a physical reduction of some dimension of the affected chemical species!

I had one of those "aha" moments and drew her a diagram of what actually happens with an example species being reduced, in this case a bare proton (a hydrogen ion, H+): H+ has an oxidation state of +1, which can be reduced by an electron donor to 0. The atomic diameter of the ion is as small as a species can get, effectively equal to the proton's diameter; the addition of an electron ("reduction") drastically increases, in a relative sense, the effective atomic diameter of the neutral hydrogen (disregarding the issue of likelihood of a monatomic non-ionic hydrogen), which is "a bigger dimension", not "a reduced dimension".

Chemistry - and most of science - is full of such interesting and sometimes annoying little ambiguities which are the legacy of discovery and provisional definition. Don't even get me started on all the different symbols used to denote "energy"...

Quote of the Day

The mind likes a strange idea as little as the body likes a strange protein and resists it with similar energy. It would not perhaps be too fanciful to say that a new idea is the most quickly acting antigen known to science. If we watch ourselves honestly we shall often find that we have begun to argue against a new idea even before it has been completely stated.

Wilfred Batten Lewis Trotter, English surgeon (1872-1939)

Never cram, always take your exams well-rested

One down, two to go: just finished my chemistry final exam half an hour ago, now time to relax and prepare myself with rest and food before my discrete mathematics exam tonight. I don't believe in cramming: I prefer to clear my mind before an exam, using the store of knowledge I've built up over the school term... that way, I know what I know when I take the test. Cramming doesn't really work, neurologically, though some people never seem to understand that observation.

It was almost funny the number of classmates who nearly physically jumped me on campus during the last half-hour before the exam, asking me questions they should have been asking the teacher weeks ago, e.g. "What does entropy have to do with Gibbs free energy?" or "What is a 'colligative property'?" or "What's the 'steric factor' in the rate constant?"

The best I could do is assure the questioners that they'd do fine, and to stop worrying: they'd be better prepared by meditating to clear their heads than to try to understand material they should have already mastered. I didn't have the heart to say, "Dude, you're so screwed!"

Remember that scene from "Real Genius"?

I took this shot two hours ago. These are the digital and tape audio recorders of a number of students in our chemistry lecture section:

Look familiar? Anyone else remember that running sight gag from the 1985 Val Kilmer flick "Real Genius"? As one writer describes the scene (yay Google, saved a bit of typing on my part):

Do you remember the scene in the movie "Real Genius" that showed students at the beginning of a university semester sitting in a large lecture room listening to the professor? As the semester wore on, one-by-one each student left a tape recorder on their seat. The scene ended with the professor's recorder pontificating to a room full of other recorders.

I found a screenshot of that scene, which looks amazingly like our chem lecture hall, down to the same phenolic resin desktop:

Whoa. Life converges on art. Fortunately, ours is a very dynamic professor... most of the students are simply trying to capture his superb lectures for replay later. As a matter of fact, on most days the professor records his own lectures with studio-quality equipment for posting on his personal website. If only more of the good ones did that, we'd have more "Feynman Lectures on Physics" preserved for posterity.

As long as the pH meter is available...

Today in lab, a couple of people broke the "no food or drinks in lab" rule. My prof - whose lab desk is next to my lab bench - and I reacted not by stating the obvious, but by saying, "Hey! Let's measure the pH of those drinks!" Why not? We all had $600 Accumet pH meters in front of us. So, we measured the pH of the following solutions:

• Gatorade X-Factor: pH 3.089
• Arizona Iced Tea brand Green Tea w/ Ginseng & Honey: pH 3.424

That's pretty interesting, since at first approximation, I'd expected any Gatorade solution to be isotonic, at a physiologic pH of ~7.42 or so. Not so, but given that the ingredients label lists citric acid and its conjugate base sodium citrate (a buffer solution), no big surprise: it's almost exactly the pH of a 0.100 M solution of acetic acid (a weak acid, with a Ka of 1.737 x 10^-5). The Arizona Iced Tea also has citric acid in its ingredient list, but no conjugate base listed (though it undoubtedly exists in solution).

Unexpected beauty on the laboratory bench

A couple of days ago I was working in the chem lab under time pressure, preparing a number of buffer solutions for a kinetics exercise prior to a tedious and time-consuming spectroscopy run. I'd very carefully delivered fixed amounts of various reagents when, at the last phase of preparation, I added minute amounts (0.3 mL each) of bromocresol green indicator (AKA 3,3',5,5'-Tetrabromo-m-cresolsulfonphthalein), this happened:

I had to stop at this moment and pull out that little digital camera I keep in my cargo pockets when I'm clothed. These little moments of unexpected beauty (to my eyes, at least) should be appreciated, and sometimes shared with friends. Here's what they looked like after mixing but before analysis:

This reminds me a bit of before and after shots of a line of carefully prepared cocktails in a Vegas casino bar.

So many sleepwalkers

This is one of those "don't get me started" moments, but I'm compelled to comment with fascinated horror at the number of fellow students who will follow the letter of a laboratory procedure but not understand in the least what is happening on the bench in front of them. I can't believe the number of students who don't understand that if they're assaying for a peak absorbance, and you don't find it in the range suggested by the lab manual, you keep measuring until and after peak until you find that crucial number. I think the term "laboratory investigation" should be stressed over "laboratory procedure." The former is science; the latter is sleepwalking.

"The system is in dynamic slinkylibrium"

I've discovered that a standard metal Slinky is not only a great tutoring tool for explaining concepts of physics such as both transverse and longitudinal wave motion, harmonics, and spring constants, but also for concepts of chemistry, namely chemical equilibrium. For those of you familiar with LeChatelier's Principle and reaction coordinate diagrams, do this: hold the ends of a metal Slinky in your hands at the same level. The activation energy for some fundamental step is represented by the high PE peak of the curve at the top. Reactants are in your left hand, products in your right. With you hands even, the enthalpy of reaction (delta H) is 0, and the Slinky oscillates around top dead center, representing an equally product-or-reactant favored reaction step. Drop your right hand, increasing negative enthalpy of reaction, and the Slinky drops quickly into the product side. Drop the left hand instead, increasing positive enthalpy of reaction, and the reaction moves toward reactants. Very cool: it's fun to watch the light of understanding in the eyes of your audience.

Speaking of Atkins again: Trader Joe's chocolate

Speaking of the Atkins diet thing again, I've found a decent-tasting chocolate bar at Trader Joe's, home of Two Buck Chuck wine. It's U.S. $1.49 for a 100gram bar of:

• Dark Chocolate - "Net Impact Carbs: 0.13g"
  
• Milk Chocolate - "Net Impact Carbs: 0.50g"
  
• White Chocolate - "Net Impact Carbs: 0.00g"
  

Maltitol has been omitted as its conversion requires little or no insulin and does not cause an appreciable increase in serum glucose levels.

It's made under contract from F.G.H. Consulting U.S.A. in Boca Raton, Florida, which interestingly was fined in May 2003 for a controversy involving false labelling. I'm assuming that Trader Joe's knows of this issue and has dealt carefully with this contractor. You can call them directly at 561-706-6178 and find out yourself. The direct manufacturer is indicated as "CHOCOLATES TORRAS S.A." of Spain, so F.G.H. is likely the trading company.

The bars do taste acceptably delicious.

Quote of the Day

If any student comes to me and says he wants to be useful to mankind and go into research to alleviate human suffering, I advise him to go into charity instead. Research wants real egotists who seek their own pleasure and satisfaction, but find it in solving the puzzles of nature.

Albert Szent-Györgi
(1893-1986)

One more before bed: phenol

I couldn't resist this: phenol.

G'nite.

Yet more on sulfites: a model of sulfur dioxide

I'm playing with RasMol, a molecular visualization tool. I'm starting with small inorganic molecules right now; since I was talking sulfites today, here's sulfur dioxide (SO₂) for you, in the standard space-filling model:

I'll be playing with RalMol some more. Visualization of macromolecules should be interesting in this tool...

"Chemistry of Winemaking", 1973, on sulfites in wine

Yesterday, I published an article by John Sebastian on the amusing topic of homemade wines done on the cheap. John made some assertions about "sulfates" (actually "sulfites") which generated some informative response from James Rogers in refutation. As a chemistry student with a burgeoning personal library on the science and some of its applications, I happened to have a copy of the proceedings of the 12-13 April 1973 "symposium sponsored by the Division of Agricultural and Food Chemistry at the 165th Meeting of the American Chemical Society" held in Dallas, Texas: "Chemistry of Winemaking", A. Dinsmoor Webb, editor (published 1974 by the ACS, Advances in Chemistry Series #137).

I've scanned in several pages of this out-of-print book, pp280-285, from the Webb article "Home Winemaking", which mention sulfite production and supplementation. I've included the section entitled "The Course of Fermentation" below simply because my OCR program flawlessly reproduced it... why waste the material by not including it? I have reproduced "Table I" manually with the published values, and placed it inline, after the first reference to it in the original text.

Those with a chemistry background will also note that this was written 30 years ago, before IUPAC nomenclature standarization.

- Russell

Excerpt follows:

Addition of Sulfur Dioxide

Certain fruits and some of the white varieties of vinifera have a tendency to brown during crushing and other early processing operations because of oxidation. This oxidation may be promoted by enzymes in the fruit, or it may be a direct reaction between phenolic material of the fruit and oxygen from air. Sulfur dioxide (SO₂) is a strong enough reducing agent that it is oxidized in preference to the phenolics of the fruit juice. Sulfur dioxide may also function by denaturing the oxidizing enzymes. Therefore, to prevent browning, add 25-200 ppm SO₂ to the fruit immediately after crushing. The quantity of SO₂ is governed by the ease of browning of the particular Juice being vinified. SO₂ in addition to preventing oxidative browning in juices, inhibits growth of bacteria and wild yeasts. Thus it provides a more nearly sterile field for the action of the desirable yeast starter added by the enologist. The quantity of SO₂ to be added to the juice is varied according to the condition of the fruit-clear, cool, sound fruit fresh from the vineyard requires very little while fruit that is in poor condition and warm needs more. The amounts of SO₂ to be added to a juice can be estimated from Table I.

SO₂ is a pungent and unpleasant smelling, dense gas at normal temperature and pressure. Under moderate pressure it condenses to a liquid which can be stored in steel cylinders. The large winery usually adds SO₂ to the crushed grapes by carefully metering a small stream of the liquid from a cylinder to the inlet line of the pump that transfers the must from the crusher to the fermenting tanks; this ensures that SO₂ is uniformly mixed into the mass of crushed fruit. For the small winery and the home winegrower, however, the relatively small amounts of SO₂ required are difficult to measure and transfer as liquid, so either water saturated with SO₂ or a SO₂-liberating salt is used.

Water saturated with SO₂ gas at room temperature contains 5-6 wt % SO₂ depending on the temperature. While the SO₂-saturated water solution is still very pungent and unpleasant smelling, it does not present the handling and measurement problems of pure liquid SO₂.

The sodium and potassium salts of SO₂ are simpler and more pleasant to use as they do not have the odor of the pure liquid or the 5% water solution. They are rapidly soluble in must [Editor's Note: this is the original wording] where they react with a small portion of the natural acid present to liberate SO₂. There are two sodium salts of SO₂ available, Na₂SO₃ (neutral sodium sulfite) and NaHSO₃ (sodium acid sulfite). The latter compound introduces less sodium into the wine and removes less acid from the wine for an equivalent amount of SO₂ liberated. Potassium acid sulfite and potassium pyrosulfite (potassium metabisulfite) are the two salts of potassium with SO₂ that are readily available, soluble in grape juice, and capable of yielding SO₂ upon reaction with the acid of the juice. Potassium salt is recommended when it is desired to keep the wine low in sodium ion content for diet reasons. The salts should be edible or food product grade, that is, free of heavy metals and other toxic impurities. They must be stored in tightly closed containers or they will react with the water vapor and carbon dioxide of the air to yield sodium or potassium carbonate and SO₂-thus losing their effectiveness as sources of SO₂ when added to the grape juice.

The required dose of SO₂ should be estimated conservatively and measured precisely because excessive amounts of SO₂ destroy the aroma and taste of the wine and can delay the onset of fermentation. Also SO₂ in excess interferes with the natural development of bouquet in red table wines and diminishes the intensity of the red color. One should always use only the minimum amount of SO₂ required to inhibit bacterial growth and counter oxidation-more definitely is not better.

Yeasts and Bacteria

One of the purposes of adding SO₂ is to inactivate bacteria and wild yeast so that the fermentation may be conducted with a chosen desirable strain of yeasts. Fortunately the wild yeast and the bacteria on grape berries (frequently confused in the older literature with the wax-like bloom which is naturally present on some berries) are susceptible to inactivation by relatively low doses of SO₂. A clear field is thus available to the large inoculum of SO₂-tolerant pure culture yeast added by the enologist.

It is true that wines were made for thousands of years before it was known that yeast was responsible for the fermentation. It is also true that in certain regions of the world wines are still made without SO₂ and pure yeast starters. These latter regions are generally those in which the yeast-containing sediments and press residues from the winery are returned to the vineyards and worked into the soil. Over many years it is likely that this procedure has resulted in the natural selection and stabilization of a mixed culture of yeasts which is carried from the vineyard to the winery and back and that the particular mixture contains enough of the desirable types to produce good wines in most years. It is also true that in years of cold summers and rainy harvest seasons many of the wineries normally relying on spontaneous fermentations use SO₂ and pure-culture starters. Today nearly all standard quality wine (vin ordinaire) and probably the majority of fine wines of the world are vinified using SO₂ and pure-culture yeast starters.

The bacteria which are found on sound grapes as they come from the vineyards are few in types and normally no problem in wine production as the acid, tannin, and alcohol of the wine stop their growth. The wild yeasts cannot be trusted to produce a good fermentation, however. In comparison with selected strains of SO₂-adapted yeasts, defects of wild yeasts are the inability to multiply rapidly in the relatively concentrated sugar solution of grape juice, a sensitivity to alcohol which prevents completion of the fermentation, a tendency to form excessive amounts of odoriferous esters or other non-alcohols, and the characteristic of remaining dispersed throughout the wine rather than aggregating and falling to the bottom of the container. The advantages to the home winegrower to be derived from the use of a selected yeast are obvious.

About 3 vol % of actively fermenting pure-culture yeast starter is required. A clean juice which has had a low dose of SO₂ will start and ferment satisfactorily with a lower inoculum, but the 3% level usually results in a quicker starting fermentation. For the home winegrower the simplest way to get the gallon or so of starter required is from a nearby winery. One has no choice of yeast strain and no guarantee of purity by this method, however. Winery supply agencies can usually furnish some strains of desirable wine yeasts such as Montrachet and Champagne in lyophyllized or freeze-dried form. These can be added directly to the SO₂-treated juice and probably represent the optimum solution to the starter problem for the home winemaker. If it is desired to use a yeast strain that is not readily available in either of the above-mentioned forms, a small pure culture of the desired strain will have to be obtained from a biological laboratory supply house or research laboratory maintaining a yeast collection. The small culture next must be multiplied until enough cells are present to inoculate the grape juice in the large fermenting tank. Sterile medium is required for the multiplication. Juice from a white grape variety of low flavor, such as Thompson Seedless, heated 30 min at 15 Ibs per square inch pressure (2 atmospheres) in a pressure canner, serves very well. The small culture is transferred from the original tube to about one pint of the cooled, aerated, sterilized juice contained in a sterilized quart jar or bottle. Avoid contamination from the hands or the surroundings. The sterile jar should be covered or plugged so that air can penetrate but dust and cells of undesirable organisms cannot-a plug of sterile absorbent cotton works well. The jar should be placed in a room or cupboard at 70°-80°F, and it should be shaken gently at intervals. Within a day or two, growth and fermentation should be evident. The juice will foam and bubble, particularly when the jar is shaken. When the culture is actively fermenting, it is transferred into 1-2 gallons of sterile juice containing 100 ppm SO₂ which after a day or two will be actively fermenting and constitutes enough starter for 25-50 gallons of Treated-treated juice. Successive fermentations can be inoculated from large batches that have fermented without difficulty although there is always the possibility of some contamination of the pure culture.

Yeasts, along with the algae, lichens, and other fungi, are known as thallophytes, a term which means they are undifferentiated plants or ones which do not have separate roots, stems, and leaves. Wine yeasts, along with most brewer's, distiller's, and baker's yeasts, are classed in the genus Saccharomyces or sugar fungus. The classification of yeasts is based on microscopic observation of their shape and forms, the way they divide during growth, and the way they respond when subjected to different test solutions of sugars or other chemicals. As scientists develop newer tools, such as the electron microscope, and as they study and classify more and more types of yeasts, it is desirable to develop further and to modify the older classification systems. Most of the wine yeasts are today put into the species cerevisiae with several strains being recognized by enologists. Many of these were formerly known as strains of S. cerevisiae var. ellipsoideus. It is quite likely that further study of the many species, varieties, and strains of wine yeasts will result in further refinements of the classifications.

Conversion of Sugar to Alcohol

Winemaking is basically concerned with the fermentation of the sugar in fruit Juice solutions by yeasts. Some understanding of the chemistry involved in the conversion of sugar to alcohol and carbon dioxide is significant not only because it engenders an appreciation of the beauty of natural processes but because it also lets us understand and control certain factors affecting the quality of the wine.

The suspension of yeast cells will be added to the must a few hours after adding sulfur dioxide-a time long enough to permit most of the SO₂ to react with juice constituents or to volatilize. The low level of SO₂ and the aeration during the mixing in of the yeast starter permit the cells to start their action in an oxygenated environment, a condition which favors their conversion of some of the sugar to carbon dioxide and water with a high yield of energy for building many new yeast cells. The yeast population increases rapidly from the inoculation level of about one million cells per milliliter to about one hundred to two hundred million cells per milliliter, one to two days after inoculation. Then, nearly all of the oxygen will have been taken from the juice by the yeast cells, cell multiplication will slow dramatically, and conversion of sugar to carbon dioxide and ethanol becomes the main chemical reaction.

Fruit juices, depending on the type of fruit, contain one or more of the three sugars, sucrose, glucose, and fructose, in relatively high concentrations. Other sugars are present in trace to small amounts. Most yeasts have an invertase enzyme on the outer layer of their cell walls which rapidly converts the sucrose to glucose and fructose. These simpler sugars are carried rapidly through the cell wall by active transport. This is not understood fully, but it is known that glucose and fructose get into the cell interior faster than they should by simple diffusion.

Inside the yeast cell the hexoses are converted principally to ethanol, carbon dioxide, and adenosinetriphosphate (ATP) with the liberation of waste heat. The ATP is an energy source in cell metabolism; the ethanol and carbon dioxide diffuse across the cell wall to the exterior where the ethanol dissolves in the juice and the carbon dioxide bubbles to the surface. Excess heat must be removed to prevent the self-pasteurization of the wine, as most yeasts cease fermentation at 40°-45°C. Minor amounts of numerous other compounds are formed as by-products.

In addition to the carbon and nitrogen which are necessary to yeast for building enzymes, a few elements such as phosphorus, potassium, magnesium, manganese, and possibly traces of others, and a few vitamins are required for growth and fermentation. Normally, grape or other fruit juice will contain all substances necessary for yeast growth and fermentation. In preparing certain special flavored wines where the main component of the mixture for fermentation may be pure sucrose, it is necessary to add a yeast food-usually a mixture of ammonium acid phosphate with some autolyzed yeast-as a source of materials required for growth and fermentation.

The Course of Fermentation

The fermentation can be followed, in a rough way, by the bubbling in the fermentation tank since carbon dioxide is a product of the reaction. However, this doesn't indicate the extent or degree of completion of fermentation. Under some conditions, fermentation will stop before all the sugar is transformed, leaving the new wine subject to bacterial spoilage; therefore it is desirable to have a simple way to follow the loss of sugar. Water solutions of sugars are more dense than pure water while water solutions of alcohol are less dense than pure water. Density determinations performed daily thus provide one measure of fermentation.

Normally a stem or hydrometer is used to determine density. Hydrometers may be scaled in many different units. In the United States, grape juice and wine densities are usually measured in Brix or Balling degrees which are density units reflecting the weight per cent of sucrose in sucrose-water solutions.

As densities vary with temperature, and as hydrometers are calibrated to be accurate at different temperatures, the fermenting solution should be warmed or cooled to near the calibration temperature for the particular hydrometer used; for precise determinations, the actual temperature should be measured and the measured density should be corrected.

In theory the fermentation could be followed equally satisfactorily by measuring the alcohol content of the solution. In fact, however, alcohol determinations are much slower and more complicated than density determinations, so they are seldom, if ever, used. It is possible for the fermentation to stop-successive density determinations showing the same value-while there is some sugar left in the solution, although this is not normal behavior for fermentations. It is good practice to analyze for low levels of sugars in all wines when they have apparently completed their fermentations.

Sober Up and Die, or Mom's Prison Wine, by John Sebastian

The following long article was submitted to me a few days ago by John Sebastian, a member of the Smith2004 discussion list. He had originally written it up as a response to someone joking about homebrew, a discussion which was itself spun off a thread about the benefits of resveratrol, a constituent of some red wines.

Here follows the version John mailed me for publication here, which I have editted only for grammar and spelling, not content. Enjoy at your own risk! By the way, it seems that there's not much in the way of actual cost savings in this technique, given the reported cost of the grape juice concentrate alone. "Two-Buck Chuck" is a perfectly adequate "10 dollar wine with a 2 dollar price tag", for those who have access to a Trader Joe's, but John's technique should still appeal to the Basement Chemist in some of us.

- Russell, editor

Sober Up and Die
or
Mom's Prison Wine
or
How to Make a Simple Cheap Wine that is Untaxed (Well, Mostly)

By John Sebastian

Yeah, yeah, I know: "loving spoonfuls" and all that. What makes it worse is that I'm often told that I'm a dead ringer for Jerry Garcia. No, I'm not that "the John Sebastian", I am this "the John Sebastian".

Well, it was the damn driver's license, it was also the cost, and - oh yeah - it was also the sulfates and other crap. Come to think of it, it was also just plain stubborn independence. It was also my wedding.

Huh?

Okay I'll make myself clear, or I'll try.

You see, I live in Tennessee, so every time I purchased beer or wine I had to show my ID. For a while I got away with showing my PADI Divers Card, but eventually all they would take was the old ball-and-chain driver's license. Call me sensitive, but at age forty-seven, I sort of figured it's my business whether I purchase beer and wine.

Eventually after tiring of trying to give civics lessons to the clerks at the grocery stores, I started brewing beer - Sebastian's All Malt - but that is another story. This story is about how to make a dirt cheap wine that is as tasty as anything you could want, indeed, a wine that you don't have to humble yourself by producing the state's slave ID to purchase, and a wine that is largely untaxed... thus even tastier.

Then there is all the added crap in commercial wines: mostly sulfates, and who knows whatever other crap some idiot somewhere decided has to go into commercial wines; I think it's to make it travel better or somesuch. In short, storebought wine gives me a headache, leaves a bad aftertaste, and upsets my stomach... well I said I'm sensitive. So I'd just about stopped buying wine from the store.

And the cost! Jeeze and bullwilliker! Tax upon tax upon tax. It's worse in the Deep South. Why, I knew a fellow once who drank so much beer that he was able to retire on the price difference by moving from Alabama to Indiana. It's basically the same here in Tennessee, where every bluenosed preacher with the ear of a legislator is also just as likely to be your neighborhood bootlegger. Not only does the state drive you to drink, but the rat-assed bastards thrive off your glorious inebriation. Disgusting.

Then there was my wedding. Well, just what does my wedding have to do with anything? It has to do with my mom. You'll remember I'd been brewing beer for quite some time. On the event of my wedding to the gracious, lovely, young, vibrant, and intelligent Aubrey, it was my determination to provide Sebastian All Malt for the hundred and fifty or so guests... no mean feat.

So, I'm on the phone with my mom doing some of the necessities for the blessed nuptials. I mention making the beer, and mom - not to be outdone - decides to provide her homemade wine.

Well, both the wine and the beer were really big hits, so I asked mom how she made her wine. That which follows below is basically her recipe without the sugar. It's not all that different from how prisoners in jail make wine, hence "Mom's Prison Wine".

But why "Sober up and Die"? Because red wine is good for you. Really good. It's magic: it has resveratrol [Editor's note: this is only true for certain red wines made from particular grapes grown under specific conditions.]. But that is really another story.

OK John! Enough. How do you make Mom's Prison Wine?

I was hoping someone would ask...

Obtain four cans of frozen concentrate for each gallon of finished wine. Make sure it's marked "100% grape concentrate"; don't buy the fructose syrup with fake grape-like stuff in it. I use generic concentrate. My cost for the concentrate to make about five gallons of finished wine is around U.S. $25.

This can be made in a one gallon glass or in food grade plastic jugs. I make mine in a five gallon glass carboy, but any food grade container that can be sealed will work fine. One 5 gallon unused plastic paint bucket and a lid that can be sealed - available at home despot or lowes - will also work.

My mom - from whom I got this recipe (thus Mom's Prison Wine) - uses empty communion wine bottles (gallon sized) - from the local Catholic Church. Quite comic, as she serves from the same bottles.

First, thoroughly clean the vessel. A little bleach in water will do, but it must then be completely rinsed in tap water to remove the bleach. [Editor's Note: if you're going to follow this suggestion of John's, be sure your bleach is unscented, i.e. contains only a dilute solution of sodium hypochlorite with no additives.] You can buy a gentle oxidizer at a wine making shop, as it's quite a bit easier to use than bleach: one simply rinses the empty vessel with it. To sum this all up: just clean and sanitize everything that will touch the wine and do so in a manner that is not toxic or otherwise affects taste.

Clean and disinfect anything that the wine will come in contact with: lids, tubing, water locks, etc. Wash your hands. Did I mention to clean and disinfect?

Add the frozen concentrate to your vessel (if you use a narrow-mouth container it helps to let the concentrate melt a bit). Fill with water to the appropriate gallonage, leaving a little room for froth, since the yeast will also need a little O2 (atmospheric oxygen) to get started.

Add a package of yeast. A good wine yeast costs $2 or so at a local wine maker's shop. I only use the best yeast, which stays alive up to a very high alcohol content. I know I am being extravagant here. The yeast is one of my costlier items. My mom uses braking yeast, but hey, it works.

Now you need some way for CO2 to exit your vessel, while excluding air, so we will use a water lock.

If you use the paint bucket for a vessel, simply drill a hole in the lid and stick some aquarium hose in the hole. Seal the gap with goo (e.g. epoxy, wax, Shoe Goo: anything non-toxic that will seal and hold the hose in the hole). The other end of the hose will go into a jar filled with water, fixed so gas will bubble out but air will not enter. A little tape may be needed to hold the hose in place. This simple water lock must be set above the vessel containing the future wine.

Of course, you can also buy a water lock called a "bubbler" that sits directly in the lid hole. A bubbler lets the CO2 out or your wine... but since the object of this exercise is to make a fine and inexpensive wine, the aquarium hose in the glass of water works just fine.

If you are instead using a jug or a carboy, use a cork with a hole drilled through it and vent off the gas through the tube in the cork.

As with the other technique, the object is to let the CO2 out of the bottle and to keep O2 in the air from getting back in and causing your yeast to make vinegar instead of alcohol.

Now, a lot of folks at this point would add gobs of sugar, but I have found this totally unnecessary... unless you like syrup. Diabetes runs in my family and I don't need to risk it. Believe me, my very, um, scientific testing - mostly done on weekends - shows without a doubt that there is quite enough sugar in the grapes to provide the yeast with everything they need.

Now seal up the entire mess.

At this point, when everything is sealed up and the water lock is in place, set the carboy down in the basement so that if any froth runs out the water lock, it's easy to clean up (WARNING: this stuff stains like crazy). The yeast has to work at moderate temperatures (too hot and you bias the yeast toward vinegar, too cold and the yeast works too slowly) for at least two weeks. You can let it go until it almost stops bubbling, down to the rate of about one bubble a minute. How long this takes depends on temperature, sugar content, pH, nutrients, and whether and how well you sing to your yeast and so on.

If your lock does froth up during this two weeks, simply remove it, clean it, and recharge with water, then set it back on the brew.

Now you siphon the wine off into sterilized containers - I use empty 2-liter pop bottles - trying to leave as much of the sediment behind as possible. You can use any food grade container that will seal against air. Remember, oxygen is the enemy; a little air in the bottle is necessary, but not much.

At this point your wine is quite alive and will be drinkable in another two weeks. The longer you wait the dryer a wine this will produce. Why, I've had some wines as old as three months!

Another warning: this process produces a gaseous wine. Use some sort of screw cap (back to the two liter cola bottles) so that you can slowly release the pent-up pressure. I open mine over a stainless steal bowl and take the first glass from the overflow.

You will have sediment in the bottom of your wine bottles, so when you serve, do so gently and try not to pour the dregs into a glass of wine. The dregs taste awful: that`s why they are called the dregs. In fact, if your wine lasts longer than mine, you'll need to pour it off into new containers or the dregs will eventually give a bitter taste to your wine in, say, three months.

I believe you will fine the finished product to be just about as good as any wine you can reasonably buy on the market. I quite prefer my wine: it has no sulfates or any other added agents. There is a difference you can both taste and feel the next morning.

You may have noticed how utterly simple this process is, and yes, it's quite true that wine making can be as complicated as you want it to be. One can adjust pH and nutrients, measure specific gravity, and on and on and on.

But you know, I've made at least a hundred gallons without all that expense and bother. It's really quite hard to keep grape juice around and not have it turn into wine. So, clean and sterilize your equipment, keep air out of the mix, and enjoy your untaxed wine [Editor's note: this is, to my understanding, all perfectly legal, as long as you don't publicly attempt to sell the product].

Let me know if anyone gives this a shot. I don't think I forgot anything, but please just ask here if you have a question.

And remember: sober up and die! This stuff is good for you, as long as you keep your blood sugar under control.

John Sebastian