Denaturation equals loss of protein function doesn’t it? Not !

In the old days when protein pretty much meant enzyme, heating them caused loss of their catalytic activity (e.g. denatured them). A more familiar example is what happens when you boil an egg — the albumin in the egg white turns into a solid (delicious) mass.

Now that we know a bit more about protein structure, it was clear what was going on when an enzyme was denatured. Consider a typical serine protease with its catalytic triad of 3 amino acids (aspartic acid, histidine, serene) which have to be correctly juxtaposed in 3 dimensional space for the enzyme to work. However, in a typical enzyme, aspartic acid is 45 amino acids away from histidine on the linear protein chain. Serine is even farther away 92 amino acids and in the other direction to boot. Heating the protein causes the chains to contain more kinetic energy, the protein chain (polypeptide backbone if you’re fancy) flops around, and the 3 amino acids separate from each other, and in the case of albumin, they never find their way back.

So denaturation came to be associated with the idea of an unstructured protein (meaning really a protein with multiple structures changing into each other all the time). For more details on this see http://luysii.wordpress.com/2010/08/04/why-should-a-protein-have-just-one-shape-or-any-shape-for-that-matter/ and http://luysii.wordpress.com/2010/10/24/the-essential-strangeness-of-the-proteins-that-make-us-up/. I find it nothing short of miraculous that the proteins making us up have just a few 3 dimensional shapes (conformations of the protein backbone), e.g. that any protein is structured at all. The two links will tell you why I think this way.

However some bacteria have a protein which functions in this disordered state. It’s called HdeA and it is found between the two layers of the cell membrane in Gram negative bacteria such as E. Coli and Shigella. The region between the two layers of the membrane is called the periplasm. The outer membrane is quite leaky, so when an animal ingests the bacterium, it is exposed to the acid conditions in the stomach (which can be as concentrated as 1 MOLAR HCl (e.g. pH = 1). This causes most normal proteins to ‘denature’ — e.g. lose their 3 dimensional shape and become unstructured.

Enter HdeA, which has a nice shape and forms a dimer at physiologic pH (e.g. around 7). When exposed to acid, the dimer splits apart and the protein becomes ‘unstructured’ — but certainly not denatured in the old sense, because it is the unstructured form of HdeA which is functional. It serves as a molecular chaperone, using its floppy protein backbone, to bind and protect other proteins which have become unstructured due to the acid pH. Amusing no? Anything not expressly forbidden, must occur (Gell-Mann on particle physics on the way to discovering the 8fold way)

Here are a few references and some gory details for the aficionado.

[ Proc. Natl. Acad. Sci. vol. 106 pp. 5557 - 5562 '09 ] HdeA is a bacterial chaperone protein found in the periplasm which is activated by pH’s under 3 (which the ingested bacteria find themselves in as soon as they hit the stomach, because the outer membrane of gram negatives is permeable to molecules smaller than 600 Daltons). It is one of the smallest chaperones known (mass 9.7 kiloDaltons). HdeA undergoes an acid-induced dimer to monomer transition. It functions as a disordered monomer without the need for ATP. Activation exposes the hydrophobic dimer interface which is critical for substrate binding). The partially unfolded character of active HdeA allows the chaperone to adopt different conformations as required for recognition and high affinity binding of different substrate proteins. So the disordered state is crucial to function and one can’t equate disordered with denatured.

[ Proc. Natl. Acad. Sci. vol. 107 pp. 1071 - 1076 '10 ] Most molecular chaperones are either ATP dependent or rely heavily on their ATP dependent chaperone counterparts (??) to promote protein folding. There is no ATP in the bacterial periplasm which is permeable to the outside. However, there is a chaperone there in E. Coli and Shigella called HdeA. It binds to substrates at low pH (preventing aggregation). When pH is neutralized, the proteins are released. Unfolding and dissociation of HdeA into monomers caused by low pH, actually activates is chaperone function by inducing the exposure of structurally plastic, high affinity binding sites for unfolding proteins on HedA, allowing it to prevent protein aggregation. Partially unfolded HdeA monomers are quite flexible, allowing it to bind to a variety of substrates, some of which are much larger than the 9.7 kiloDalton HdeA itself. Inactivation of HdeA is triggered by pH neutralization, which induces its refolding and dimerization.

Next up, two background posts and then a longer post on the most interesting paper I’ve read in the past 5 years.

How to spread the new H7N9 flu

People are naturally nervous about the new strain of influenza virus (H7N9) which, as of 5 April had killed 6 people. Eerily the new flu emerged in Asia almost exactly 1 decade after the SARS epidemic. The causative agent of SARS is a Coronavirus, a completely different virus from influenza. To add to the confusion, in the past 9 months a new strain of Coronavirus has emerged in the Middle East, with a high initial case fatality rate (11/16).

My wife and I were in Hong Kong for the past few weeks for a happy family event, and the horror of the SARS epidemic was widely reported on TV and newspaper (interviews with survivors etc. etc.). I’d estimate that, on any given street in Hong Kong, Beijing, Kyoto, Osaka between 1 – 5% of people are wearing masks covering their nose and mouth. This was not a reaction to the news of the new flu (which came out only 6 days ago), but an attempt by those ill with any febrile illness to avoid spreading it.

First, a bit of reassurance. The most severe cases of any epidemic are always the ones by which it announces its presence. So the high case fatality rate (6/16) reported so far almost certainly won’t hold up. Later on, after the causative organism has been identified, and the immune response to it worked out (involving proteins attacking the bug — e.g. the antibodies), we always find that there were hordes of people who had only a mild illness or who weren’t sick at all (except for AIDS, but even there the most severe cases came to light first). However you don’t need a high fatality rate for an epidemic to be lethal — the 1918 flu had a case fatality rate of 10 – 20% yet it killed between 50 and 100 million people.

You couldn’t come up with a better way to spread a respiratory virus that what happened at JFK airport at two midnights ago (it’s the morning of the 6th here in the USA). Two large flights arrived at about the same time — the Cathay Pacific flight we took from Hong Kong had around 200 people. The other flight seemed equally large. Everyone had to go through immigration, showing passports etc. So upwards of several hundred people came off the planes and into a corridor perhaps 15 – 20 feet wide 10 feet high and several hundred feet long. There was one immigration official for US citizens and perhaps 2 more for the non citizens. So there we were, for well over an hour packed cheek by jowl in this space as people were processed through.

If you can think of a better way to spread an infectious virus between a group of unrelated people who will disperse all over New York City, and probably all over America, I’d like to hear it.

Off to China in the Morning

Not much blogging in the past few months, not that there hasn’t been fascinating stuff to write about. Fortunately happy family events have kept me away.

The 40s seem to be the new 20s, as 3 family members are getting married in the next few months at ages 42, 45 and 46. We’re off to a Chinese Wedding Banquet for our oldest and his wife, followed by a wedding of our niece, followed by a wedding of our youngest son — all in the next 3 months. So stay well and keep thinking.

I am sweating the health of any progeny to emerge. For why, see the following post http://luysii.wordpress.com/2012/08/30/how-fast-is-your-biological-clock-ticking-ii-latest-results/

Q. E. D

The following are from two posts in August 2011, two months after Chavez first let the world know he was being treated for cancer.

My opinion of docs who diagnose over the phone, or who render opinions on people they’ve never seen is not high, although we all indulge in this from time to time. The worst example is that of the

1,189 PSYCHIATRISTS SAY GOLDWATER IS PSYCHOLOGICALLY UNFIT TO BE PRESIDENT! That determinedly flamboyant headline dressed the cover of Fact magazine one month before the presidential election of 1964. The entire issue was an examination of the “unconscious of a conservative,” based largely on answers to a questionnaire sent to the 12,356 psychiatrists listed by the American Medical Association. Of the 2,417 who replied, 657 said Barry Goldwater was fit for the presidency, 571 declined to take a position, and 1,189 called him unfit—the latter in no uncertain terms. Some of their opinions: “emotionally unstable,” “immature,” “cowardly,” “grossly psychotic,” “paranoid,” “mass murderer,” “amoral and immoral,” “chronic schizophrenic” and “dangerous lunatic.” One psychiatrist even felt that a proposed Goldwater visit to Hitler’s Berchtesgaden “is enough to convince me of his strong identification with the authoritarianism of Hitler, if not identification with Hitler himself.”

The unprofessional—not to say unbalanced—nature of such remarks brought immediate condemnation from the A.M.A. and the American Psychiatric Association. It said more about the state of American Psychiatry at the time than it did about Goldwater.For more details see: http://www.time.com/time/magazine/article/0,9171,838361,00.html#ixzz1WemleKVu

But here I am, about to indulge in the same thing concerning a very public figure. Why? Because what I’m about to say has received absolutely no attention in the press that I can find. First, look at these 3 pictures of Hugo Chavez.

http://www.guardian.co.uk/commentisfree/2011/jul/24/hugo-chavez-cancer-popular 24 July

http://www.guardian.co.uk/world/2011/aug/01/hugo-chavez-hair-cut-venezuela 1 August

http://www.guardian.co.uk/world/hugo-chavez 31 August

What’s the point? The rather remarkable change in his facial appearance over this short period of time. In just 6 weeks or so he has developed the classic face of someone receiving very high doses of corticosteroids (Cushingoid facies). The loss of hair due to his chemotherapy is irrelevant — it happens to most and is reversible when the chemo stops.

It also implies either that his docs are grossly overtreating him or that he is a very sick man. Doses of corticosteroids high enough to produce such massive facial change should never be used lightly. Back in the day, this was all I had for the flareups of multiple sclerosis, and it was never easy on patients.

We do not know what sort of cancer he has, if it has spread, and if so, how far. If his cancer was curable don’t you think it would have been trumpeted in one of his nearly daily press releases?

More worrisome for Chavez, is the fact that high doses of corticosteroids, invariably produce side effects. One you are seeing — the change in facial appearance. Two others are the invariable worsening of diabetes (should he have it) and the much increased possibility of stomach ulcers and bleeding. Both are fairly easily managed, particularly ulcers — none of my MS patients ever got ulcers because I began treating them as if they already had one (e.g. milk and maalox) when I started the corticosteroids. This was long before we know about Helicobacter and ulcers

High doses of corticosteroids usually produce a sense of euphoria. Cognitive processes aren’t as good, and they are one of the few known causes of reversible cerebral atrophy.

Far more worrisome for Venezuela and the rest of us, is the psychosis occasionally seen with high doses of corticosteroids. He is a man of enormous power, and hopefully no one has given him nuclear weapons.

So like my Cuban friend’s mother who prays for Castro’s health because her mother (who played cards with him when they were both young) is determined to outlive him, we must hope for a peaceful conclusion to Hugo’s illness.

From another post in August 2011

Also if he had a curable form of cancer, don’t you think he’d have told us exactly what it is? More likely, he’s putting on a front so his regime doesn’t collapse. Years and years ago I was a member of the Council on Foreign Relations in a western town. Various speakers were brought in — General Maxwell Taylor, etc. etc. The most interesting was the current Egyptian ambassador (or an attache). He said that the governments in the mideast were all ‘one bullet governments’ — which was all it would take to change their direction radically –all were run by one man at the top — this before the assassination of Anwar Sadat.

At least we see Chavez. Recall the last hospitalization of Yasser Arafat in France. We were told that everything was going well. What we were not told until very late, was that all this information was from the family and not from the people taking care of him. The investigative press was nowhere to be found.

This is unlikely to change. The powerful will always be able to warp the medical system to their desires. Think Michael Jackson, or even president Woodrow Wilson (incapacitated by a variety of strokes in his last years in office).

Now on to the present.
We are told by Chavez or someone permitted to speak for him, that he has a 2 centimeter lesion, either at the site of the old surgery or near it. Assume, for better or worse, that this is true. What does it mean? Well, one of three things:

1. Stop calling this a lesion. Only tumors act like this. No one gives chemotherapy enough to make your hair fall out for ‘lesions’ that aren’t tumors.

2. They couldn’t get the whole tumor out (meaning it’s incurable), and despite the high doses of steroids he’s on (recent pictures of him show his face even more Cushingoid than the 3 cited above) the tumor has grown further and needs to be removed (for any of several reasons, none of which is good).

3. At the time of the initial surgery, they thought they had removed the tumor, and the present 2 centimeter lesion has grown from something they didn’t see, because it was too small. Assume that what they missed was 1 milliMeter in diameter. Anything larger wouldn’t have been missed (assuming the people operating on him were competent — but ask Fidel about that — he’s still recovering years later from whatever they did). Since the lesion now 2 centimeters, this means that its volume in milliMeters is 4188 cubic milliMeters (4/3 pi r cubed, with r = 10). This is roughly 12 doublings of the tumor, or around 1 doubling every 17 days. The chances of a benign tumor growing this fast are remote (although my late mother had exactly that in her pelvis and lived another 40 years).

Are molecular oncologists looking under the lamppost?

There’s an old joke about a drunk who lost his keys coming home from the bar one night. Daybreak found him still crawling around searching under a lamppost. A passerby asked him why he didn’t look elsewhere. Drunk’s answer: “That’s where the light is”

The molecular biology you need to understand the following can be found in the 5 posts in the “Molecular Biology Survival Guide”. Here’s the link http://luysii.wordpress.com/category/molecular-biology-survival-guide/

The parts of the genome we understand the best are the parts that code for protein. The Cancer Genome Atlas spent a lot of money (1.5 Billion $) looking at genes coding for protein. They started with the most highly curated (translation: hopefully valid) set of genes. There have been tons of papers coming out of the project. Unfortunately, all we know is that every cancer studied so far has lots of mutations in the protein coding genes (the average breast or colon tumor has 90+ such mutations). Many of the mutations found were in previously known cancer causing genes (oncogenes). It would be great if, say, the same few genes were mutated in a given type of cancer. Unfortunately this isn’t the case. There is very little overlap in the mutations between two tumors of the same type. Of course this bears out the well recognized clinical fact not all tumors from organ X (say breast) act the same, even when they are sub classified by the way they look under the microscope (histological type).

This brings us to [ Science vol. 339 pp. 957 - 959 - 961 '13 ]. Once you venture away from the parts of of the genome coding for the amino acids of a protein, the next best understood parts, are those immediately in front (5′ to) the gene itself. The closest element is called the promoter, and is usually within 100 base pairs of the site at which transcription of DNA into RNA begins. Then farther out (sometimes thousands of base pairs out) come the enhancers, which help transcription factors do their work.

TERT is a protein which helps to keep the ends of chromosomes (telomeres) intact. This work looked at the promoter rather than the protein itself, and found two mutations. Together they were found in an astounding 50/70 melanomas, and 24/150 of a variety of cancer cell lines. I think this is much, much higher than any particular oncogene was found mutated in the Cancer Genome Atlas. The net effect of the two mutations was to make binding of a type of transcription factor (ETS) easier, resulting in more TERT being made.

So it’s time to start looking at the 98% of the genome NOT coding for protein. The problem with looking here, is that we really don’t know what it’s doing. The days when it was called junk are mercifully behind us. The second problem, is that we’re going to find changes from the ‘standard’ genome (which really doesn’t exist — the average infant contains 30 mutations not present in either parent) and we have no clue as to how to interpret them.

Everett Koop M. D. RIP

Not many outside medicine know just what he did before becoming surgeon general and famous. He essentially invented the subspecialty of pediatric surgery. Sure, surgeons had been operating on kids from time immemorial, but that’s all Koop did. One of his triumphs was esophageal atresia, meaning that in a newborn part of the esophagus was either absent or too small to pass even fluids, meaning death. The size of the organ in the newborn is a pencil or smaller, and Koop figured out a way to replace or hook up (anastomose) the parts of normal size.

As a med student in Philly, I was lucky enough to make rounds with him at CHOP (Children’s Hospital Of Philadelphia) in the 60′s. He was a typical Pennsylvania Dutchman, very solid, no nonsense, serious, not pompous, rather reserved.

Probably the most accomplished Surgeon General we’ve ever had. I was particularly appalled when Senator Ted Kennedy mau-mau’ed him. Koop was devout and against abortion, and the attacks on his character by the hero of Chappaquiddick were disgusting to those of us who knew him.

Even though Reagan didn’t want him to do it, he was very outspoken about AIDs, and didn’t try to sweep it under the rug as a punishment from God etc. etc. This prominent and early focus probably saved millions of lives, as ignoring it, would have just helped it spread even faster and farther. This is basically the physician’s focus — to deal with the world as it is, not as we wish it to be, and do what we can even for those whose behavior brought misfortune on them. Koop was just being a doc.

To Kennedy’s credit, he later apologized to Koop.

The weird way human memory works — Hopfield was right

Sometimes middle of the night thoughts are strange.  At 3AM today, I was trying to remember the name of the guy who wrote “Infinite Jest” and “The Broom of the System”.  The only thing that kept popping into my head was Richard Gordon Loomis, the name of my very excellent piano tuner, but a man with no known literary inclinations. I had no idea why this happened until I came up with the real name of the author this morning, 5 hours later — David Foster Wallace.

They don’t sound the same (except for the last syllable), but they have exactly the same rhythmic cadence of syllables when spoken.  Also he’s the only person I know who uses his middle name (the reason being that, amazingly enough, there is another piano tuner in the area named Richard Loomis).

This fits with John Hopfield’s theory of memory (he’s one of the inventors of the neural net) — having to do with chaos and attractors ( Neural networks and physical systems with emergent collective computational abilities. Proc. NatL Acad. Sci. USA Vol. 79, pp. 2554-2558, April 1982).   Just get anything near what you are trying to remember, and slowly (5 hours in this case), it converges to what you are trying to remember (an attractor in memory space).  It does show just how even peripheral parts of a concept (the cadence of what you are trying to remember when you speak it) are part of the concept itself.   Clearly, concepts are multidimensional.

Retinal physiology and the demise of the pure percept

Rooming with 2 philosophy majors warps the mind even if it was 50 years ago.  Conundrums raised back then still hang around.  It was the heyday of Bertrand Russell before he became a crank.  One idea being bandied about back then was the ‘pure percept’ — a sensation produced by the periphery  before the brain got to mucking about with it.   My memory about the concept was a bit foggy so who better to ask than two philosophers I knew.

The first was my nephew, a Rhodes in philosophy, now an attorney with a Yale degree.  I got this back when I asked –

I would be delighted to be able to tell you that my two bachelors’ degrees in philosophy — from the leading faculties on either side of the Atlantic — leave me more than prepared to answer your question. Unfortunately, it would appear I wasn’t that diligent. I focused on moral and political philosophy, and although the idea of a “pure precept” rings a bell, I can’t claim to have a concrete grasp on what that phrase means, much less a commanding one.

 Just shows what a Yale degree does to the mind.

So I asked a classmate, now an emeritus prof. of philosophy and got this back

This pp nonsense was concocted because Empiricists [Es]–inc. Russell, in his more empiricistic moods–believed that the existence of pp was a necessary condition for empirical knowledge. /Why? –>
1. From Plato to Descartes, philosophers often held that genuine Knowledge [K] requires beliefs that are “indubitable” [=beyond any possible doubt]; that is, a belief counts as K only if it [or at least its ultimate source] is beyond doubt. If there were no such indubitable source for belief, skepticism would win: no genuine K, because no beliefs are beyond doubt. “Pure percepts” were supposed to provide the indubitable source for empirical K.
2. Empirical K must originate in sensory data [=percepts] that can’t be wrong, because they simply copy external reality w/o any cognitive “shopping” [as in Photoshop]. In order to avoid any possible ‘error’, percepts must be pure in that they involve no interpretation [= error-prone cognitive manipulation].
{Those Es who contend  that all K derives from our senses tend to ignore mathematical and other allegedly a priori K, which does not “copy” the sensible world.} In sum, pp are sensory data prior to [=unmediated by] any cognitive processing.

So it seems as though the concept is no longer taken seriously.  To drive a stake through its heart it’s time to talk about the retina.

It lies in the back of our eyes, and is organized rather counter-intuitively.  The photoreceptors (the pixels of the camera if you wish) are the last retinal elements to be hit by light, which must pass through the many other layers of the retina to get to them.

We have a lot of them — at least 100,000,000 of one type (rods).  The nerve cells sending impulses back to the brain, are called ganglion cells, and there are about 1,000,000 in each eye.  Between the them are bipolar cells and amacrine cells which organize the information falling on the photoreceptors.

All this happens in something only .2 milliMeters thick.

The organization of information results in retinal ganglion cells responding to different types of stimuli.  How do we know?  Impale the ganglion cell with an electrode while still in the retina, and try out various visual stimuli to see what it responds to.

Various authorities put the number of retinal ganglion cell types in the mouse at 11, 12, 14, 19 and 22.  Each responds to a given type of stimulus. Here are a few examples:

The X-type ganglion cell responds linearly to brightness

Y cells respond to movement in a particular direction,

Blue-ON transmits the mean spectral luminance (color distribution) along the spectrum from blue to green.

From an evolutionary point of view, it would be very useful to detect motion.  Some retinal ganglion cells being responding before they should. How do we know this?  It’s easy (but tedious) to map the area of visual space a ganglion cell responds to — this is called its receptive field.  The responses of some anticipate the incursion of a moving stimulus — clearly this must be the way they are hooked to photoreceptors via the intermediate cells.

Just think about the way photoreceptors at the back of the spherical eye are excited by something moving in a straight line in visual space.  It certainly isn’t a straight line on the retinal surfaced.  Somehow the elements of the retina are performing this calculation and predicting where something moving in a straight line will be next.  Why  couldn’t the brain bedoing this?  Because it can be seen in isolated retinas with no brain attached.

Now for something even more amazing.  Each type of ganglion cell (and I’ve just discussed a few) tiles the retina. This means that every patch of the retina has a ganglion cell responding to each type of visual stimulus.  So everything hitting every area of the retina is being analyzed 11, 12, 14, 19 or 22 different ways simultaneously.

So much for the pure percept: it works for a digital camera, but not the retina.  There is an immense amount of computation of the visual input going right there, before anything gets back to the brain.

If you wish to read more about this — an excellent review is available, but it’s quite technical and not for someone coming to neuroanatomy and neurophysiology for the first time.  [ Neuron vol. 76 pp. 266 - 280 '12 ]

Making an enzyme do a carbene reaction

The P450 cytochrome enzymes are the chemical workhorses of biosynthesis and xenobiotic detoxification.  As a neurologist I always had to worry about the way adding a new anticonvulsant to a an existing set would alter the body levels of all of them.  The new anticonvulsant would cause the P450 cytochrome enzyme metabolizing it to increase, and the new P450 might also chew up some of the others.  Phenobarbital was a particular problem this way.

Over 14,500 P450 genes have been found in various organisms. FYI the 450 in P450 comes from the absorption at 4500 Angstroms of the Fe++ in the heme group when complexed to carbon monoxide.  This is called the Soret band.  The P450 cytochromes are a superfamily comprising 36 known gene families, each consisting of 2 -20 discrete cytochromes.

The P450 cytochromes take 2 electrons from a reduced cofactor (NADPH) which itself gets the electrons from another molecule.  The cytochrome then binds an oxygen molecule splitting it so an oxygen atom is bound to the Fe++  (the other oxygen goes to water).  The oxygen is then used by the various enzymes to insert into C-H bonds with an incredible specificity (this produced by the conformation of the protein around the heme-iron-oxygen).

In Science vol. 339 pp. 283 – 284, 307 – 310 ’13 a group at Caltech which has been using direct evolution (randomly mutate a protein and select for the reaction you want) used a P450 cytochrome to accept diazo esters as reagents.  This formed a carbene linked to the Fe.  They found that it would add to olefins.  Further engineering (random selection actually) produced variants of the P450 to produce diastereoselective and enantioselective cyclopropanation of styrene.

It would be nice to see the crystal structures of the engineered enzymes carrying out the reactions, to see how they constrain the styrene to react so specifically.

So here we have chemists acting like the blind watchmaker of Dawkins.  It would be nice if theory was good enough to predict and design the P450 variants produced here a prioi, but it isn’t.  The editorialist calls it biomimicry in reverse.

A solution to America’s obesity problem

Who knew it would be that simple?   Not only that, but the same country has figured out a way to give anyone who wants one, an absolutely free college education.  Interested?  Read on.

These thoughts occurred after listening college classmate, lecture to a bunch of us alums about a trip he took to a foreign country a few months ago, along with 15 or so of our classmates and their wives.  He’d been in the foreign service and had even served as an ambassador to a nearby state.

All is not sweetness and light however.   Housing is scarce, and newlyweds have two choices about where to live — with the groom’s parents or the bride’s.

Vintage car fans love the country, and one of his slides showed a Chevy from my youth in the 50s.

Ecologists love the fact that the country has a very low carbon footprint.  Even though 20% of the population is involved in agriculture, mechanization hasn’t taken over, and draft animals abound.  The fields shown looked quite lush.  They get plenty of rain.

One of the slides was of a food distribution center.  Mayor Bloomberg would be pleased.  No junk food.  Well, actually very little food and the shelves looked rather barren.  This is where people go to get their free food.  A slide was shown of one of the ration books currently in use.

Well the food is rationed.  How else are you going to stop people from eating like pigs?  The talk was fascinating and went on for an hour with numerous slides.  Perhaps 100 or so denizens of the country appeared in them.  None were fat.  Hosanna ! !

My classmate rattled off the current rations, but it went by to fast for me to reproduce.  Hopefully he’ll fill me in.

What with the free college and all, there has to be someone paying for it.  There is — the graduates.  They all get 20 dollars a month salary, and the taxi driver of the vintage Chevy was a chemical engineer.  85% of the populace works for the government.  My classmate found this arrangement heartening, as it made just about everyone an entrepreneur (to survive).

People worried about discrimination against the elderly will appreciate the fact that pay (say 20 a month vs. 15 vs. 10) is strictly on the basis of seniority.  No silly merit pay for them.  This has the expected effect on output.

Those upset about the disparities in income and wealth here will find true equality nirvana over there.

Medical care is universally available and free.  Quality is difficult to ascertain.

This paradise is only 90 miles from Florida.  It’s called Cuba.

 

We do have one comparable institution in this country where

l. all are equal

2. food is free

3. housing is free

4. medical care is universally available and free

5. no Republican has ever stolen an election

It’s called prison.