Wednesday, 1 July 2015

Money in circulation









Supplementary material

The quest for eternal youth, or at least for a slowed-down decay, has always been a strong motivation for explorers and researchers, be they Ponce de León, calorie-restriction aficionados or a fictional Dr. Obispo. Be the solution anti-wrinkle creams, dietary supplements, spinach and turmeric smoothies or jogging, we're pretty much ready to try it all to prolong our stay on this mortal coil.

In the lab, we try to decipher the riddle of aging; how is it that some species age more slowly than others? How is it that some individuals age faster? How can we control cellular senescence to better our lot as individuals? This is all fascinating in and of itself, and may have practical applications too. (Hey, I ain't proud... I'd like to live longer as much as anybody else!)

Recent work using the technique of parabiosis has led to quite startling observations in the field of aging. Parabiosis is a technique by which the circulatory system of two animals are linked, so that the blood of one mixes with that of the other. (Naturally, the animals in question had better not be immunologically incompatible)!

More specifically, the experiments I refer to played with the age of the parabiotes, linking an old mouse with a young one (as well as two young ones and two old ones together as controls). This connection of old and young mice is called heterochronic parabiosis. The idea was, succinctly put, to see whether there was something in the blood of old mice that caused their tissues to age (think "accumulation of garbage") and whether there was something in the blood of young mice that kept them young (think "youth serum"). In the first case, it was expected that the unknown noxious factors present in the blood of the old mouse would cause its younger counterpart to show increased signs of aging. In the other case, it was possible that aged tissues would show signs of rejuvenation because of whatever came from the blood of young mice.

The results were noteworthy, to put it mildly: there was indeed something in the young blood that could cause the rejuvenation of several systems and tissues in the old mouse, without the young one apparently suffering for it. (This latter point seems to be slightly less true with increasing age for the "old" parabiote). The circulatory system of the old guy seemed to regenerate itself more efficiently, its cognition was increased, it showed lower stem cell depletion, its age-related cardiac hypertrophy was diminished... nothing but good news!

Further analysis of the phenomenon identified a particular protein that seems to play an important role in this Foutain of Youth effect: the signalling protein GDF11. This circulatory factor sees its level drop with increasing age, a drop that parallels progressive cardiac hypertrophy. Restoring GDF11 levels reverses the hypertrophy. GDF11 will also induce vascular remodelling that leads to increased neurogenesis.

Two papers on GDF11 and its amazing effects were seen as the 2014 breakthrough of the year in the biomedical field by the journal Science:

Sinha et al. (2014) Restoring Systemic GDF11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle. Science 344, 649-652

Katsimpardi et al. (2014) Vascular and Neurogenic Rejuvenation of the Aging Mouse Brain by Young Systemic Factors. Science 344, 630-634

Spookingly, the discovery that it is possible to make old individuals younger by using the blood of younger ones is the same concept that was the basis for the science-fiction novel Bug Jack Barron, written by the amazingly creative Norman Spinrad in 1969. In that story, old rich people could be made to live forever thanks to an extract made from unspecified glands in the body of young children (who, for dramatic purposes, were killed in the process).

Hopefully it won't come to that! Using the blood of the young to keep the old alive is basically what vampirism is all about! I'll settle for some recombinant GDF11, thank you.



Friday, 19 June 2015

Scaling up










Supplementary material

Floods in Mesopotamia

One of the earliest civilizations to use the written language and to leave stories that later generations could read developed in the plain between the rivers Tigris and Euphrates. I view it as both incredibly romantic and a little sad that some of these stories, which came down to us in the form of clay tablets covered with cuneiform signs, are lacking a few sections because the clay broke over a few lines. In some cases, we can patch the holes in tha narrative thanks to other tablets telling the same tale, but in several instances those parts of the story are lost forever. In an era of moveable type or infinitely reproducible electronic texts, the concept of a line being lost forever is quite outlandish and emphasizes how precious each and every artefact from antiquity actually is.

The fabulous and fertile region between the Tigris and the Euphrates was named Mesopotamia by the Greeks, which means appropriately enough "between rivers". Naturally, as many rivers do, the Tigris and the Euphrates sometimes caused floods. So did the Mississippi, one would imagine, but back then people in the Americas had no written language that we know of.

Such floods could be important enough to be considered catastrophic; enough to cause important political changes to society and mark the imagination. To wit, a list of Sumerian kings written in the late third century BCE describes how central power passed from one city to the next due to conquests, one city after the other ("...then Larak fell and the kingship was taken to Sippar" and so on) until a great flood had the same effect, causing the kingship to move to the city of Kish. That was clearly a big deal; I mean, the text takes pain to mention "the great flood".

Archaeological digs in the region reveal evidence for several such floods, as determined by the presence of at least four thick layers of clay at different depths.

What do you do when you're living near an important body of water that suddenly bursts its banks and starts covering your land? Personally, I'd jump on a boat with as much of my stuff as I can. And that's what several characters from ancient stories did!



Atrahasis

The Epic of Atrahasis is known thanks to the work of scribes who left us a few versions, one written in Assyrian and two in Babylonian. One of the latter two goes back to the reign of king Ammi-saduqa of Babylon (1647-1626 BCE). It's arguably one of the earliest stories we're still telling.

In this story, some time after the creation of mankind, the great and divine Enlil (god of the wind among other things) started finding us way too annoying. "The noise of mankind has become too much; I am losing sleep over their racket", said he, with all the irrascibility of someone who's constantly woken up when trying to get a good night's sleep.

The answer to Enlil's conundrum was not a pair of divine earplugs, but a mankind-destroying plague. Luckily for us the god of fresh waters, Enlil, advised the mortal (but extremely long-lived) Atrahasis to get his people to pray to Namtara, the plague god, who was apparently sensible to such sudden attention. Thus was our complete doom averted.

Twelve centuries later, our numbers had grown again and we hadn't become more quiet; this time, Enlil sent us a killing drought. Enki advised Atrahasis to start praying to Adad, god of the thunderstorm, who ended up sending rain after a long and dry spell. Good thing that this Atrahasis fellow was around in those days!

After another twelve centuries had passed humanity was still as noisy as ever, and a sleep-deprived Enlil, cranky as can be, decreed that enough was enough and that no god was going to help mankind this time. Anu and Adad would guard heaven, Enki would guard the waters, he himself would guard the earth and nobody was allowed to let any food reach mankind's hungry mouths. So there! There is no bread? Let them eat cake... PSYCH! The cake is a lie!

But the mankind-friendly Enki apparently cheated, and after many years of famine where people would eat their own children, he allowed plenty of fish to swim in the two great rivers and put an end to our unpleasant ordeal.

"You what"? shouted Enlil in Sumerian. Very upset with Enki breaking ranks with the other gods, Enlil ordered him to destroy mankind with a great flood (Enlil being, as we mentioned, boss of the waters). Grudgingly, Enki had to go through with this genocidal plan; he did warn Atrahasis about it, though. Or... not quite. Since Enki had sworn not to interfere with Enlil's plans, the clever god (who should have been god of lawyers, really!) spoke not to Atrahasis, but to Atrahasis's house's walls! Thus was the letter of the oath respected.

Atrahasis was told to tear his house down and build a roofed boat. Aboard he took his family, plenty of food (he slaughtered sheep and cattle for the occasion); he also brought his farm animals and all the beasts he could find on the steppe. Then it rained for seven days, and at the end everybody else was dead. But then the joke was on the gods, for without farmers there was nobody left to offer them sacrifices! And so when they realized that Atrahasis and his family were still around, they allowed them to prosper. With a few big caveats, though! To limit the noise mankind makes, we were granted things like shorter lives, difficult childbirth and infant mortality.

Sources:

Archaeological evidence for the great mesopotamian floods; the story of Atrahasis; the epic of Atrahasis and the flood. Many thanks to those who took pain to put up those sites.



Utnapisthim

The story of Atrahasis is told again in condensed form in the epic of Gilgamesh, king of Uruk, chronicled as early as 1200 BCE in Babylon. In the course of his travels, the adventurer king encounters Utnapishtim, the survivor of the great flood, whom the gods have later deified.

As in the epic of Atrahasis, the gods meant to put an end to humanity's incessant noise. Utnapishtim, a favorite of the great god Ea, was told to tear down his house and build a boat with a roof; said boat was to be as wide as it was long (which is interesting, considering that Iraqis still build round coracles. But perhaps the boat was a cube instead).

Aboard that boat, Utnapishtim had brought his family and the seed of all living things. The thing was massive, naturally: 10 times 12 cubits on a side, which translates as 60 meters, give or take. (By way of comparison, the RMS Queen Elizabeth is 314 meters long, 71 meters high and 36 meters wide). Utnapishtim's ark had six decks divided in nine compartments, and tons of bitumen and oil were used to make it waterproof. He then took aboard all that he had, including all his family, all his gold, all his silver and all his field animals; he also brough the craftsmen who had built the boat, which was the least he could do considering they apparently constructed it all within a week, drunk. (Yes, drunk. It is precized that Utnapisthim took good care of his workers, and kept them supplied with so much ale and wine during the project that they partied like it was New Year's festival).

Then it rained for seven days and the earth was flooded. When the sun returned, Utnapishtim released a dove in the hope that it would find dry land, but the bird returned unsuccessful. Utnapishtim tried the same thing with a swallow, which also returned after finding no landing spot. Then a raven was sent, and the bird saw the waters retreating and didn't come back.

Utnapishtim offered then libations to the gods, but as expected Enlil was quite pissed off that humanity had survived. He was however talked down by Ea, one of the big-time Mesopotamian gods, who reproached him his extreme measures; there were, after all, less destructive ways to keep down the noise that humanity made (such as sending it lions, wolves, plagues and famines). Note that in this version of the tale, Enlil went straight for the flood instead of cranking up successive punitive measures as in Atrahasis' tale.

Source:

The epic of Gilgamesh.



Noah

The same story is told again in the book of Genesis. This time around, mankind is not so much noisy as naughty; Yahweh decides to do away with the lot of them, and also every other living thing while he's at it, by causing it to rain for forty days and causing a great flood. (All these divine plans seem to overlook the existence of fish, marine mammals, crustaceans and waterfowl... but that's not mentioned in any of the books).

Luckily there was at least one good guy left among us evil people back then: Noah, who was told to build a great ship of cypress wood covered with pitch. The boat wouldn't be a cube, this time, but would be roughly 150 meters long, 25 meters wide and 15 meters high. Aboard Noah would bring his wife, his sons and his sons's wives, as well as "of every living thing, of all flesh, a pair of every kind, male and female, to keep them alive with him". (This would unfortunately exclude the whiptail lizard Cnemidophorus neomexicanus, which is an all-female line reproducing by parthenogenesis. A criticism to which Noah probably replied "oh, for crying out loud"!)

This time around the rain lasted forty days, and the flood itself one hundred and fifty, which (word of advice to Enlil, here) is a much safer bet that a mere week if you intend to kill every living thing in the world.

Then Noah's ark came to rest on top of Mt. Ararat in Turkey, and he sent out a raven who couldn't find a dry spot. Noah next sent a dove, which brought back an olive leaf, showing not only that the planet wasn't completely flooded anymore but that olive trees had managed to grow back instantly.

Noah offered sacrifice to his god, then planted a vine, made wine and got drunk. One of his sons, discovering Noah in such an embarrassing state, was cursed for his trouble; he and all his issue too. I ask you, is that fair?





Thursday, 28 May 2015

Won't anyone think of the children?









Supplementary material

Statistics Canada, table 102-0540, chapter XX (year 2011)

Number of people killed by falling on or from steps or stairs: 396

Number of people killed by some other fall from the same level: 856

Number of people killed while riding a bicycle: 87

Now please, help me understand why our government and many well-meaning activists are going apeshit about bicycle helmets and not about stairs and sidewalks. Riding a bicycle is barely twice as dangerous as taking a bath (41 people drowned in their bath in Canada in 2011). In the name of safety, are we going to force people to wear a floating jacket when taking their bath?

It's like a moral crusade... some worthy cause (protecting people) that becomes way more important in the eyes of its proponents than it is in reality. And the numbers be damned, because we know we're right. Case in point, here is an anecdote about a child who fell down the stairs and broke her skull, only to drown in her bathtub the next day. Do you want that to happen to YOUR child?