Tuesday, 29 April 2014

The argument from beauty

Supplementary material

The argument from beauty actually exists. Personally I find it a bit illogical because of two main things: (a) beauty is mostly in the eye of the beholder,and I seriously doubt that there is any aesthetic experience (including the very popular sunset) that triggers a universally positive response; (b) Nature is far from perfect. Oh, sure, it functions, and it functions quite well indeed; but unlike a well-made watch (tip of the hat to William Paley) nature is clearly a hodgepodge of different systems that show little sign of having been made to work together, but that managed either not to interfere too much with each other or to exploit each other to gain some kind of advantage. But let's talk of perfection to kids with leukaemia, to people with Alzheimer's disease, to people whose genes made them handicapped, or blind, or deaf, or just plain clumsy; let's talk of perfection to mothers who lost five kids in a tsunami or a mudslide; let's talk of perfection to the lost fauna of the Permian or to the hapless caterpillars that are used by wasps as living incubators (and living pantries) to the wasp's larvae... If I had a watch that ill-made, I'd return it to the watchmaker and ask for a refund. Unless, as is the case with nature, there is no other option but to endure it, even with all its imperfections. I can forgive Mother Nature for sloppy work, because no one argues that she is an actual, omnipotent and wise creator. Not so for religious alternatives.

The anthropic principle is another argument that some use to claim that the universe was essentially "made for humans". After all, they argue, we are here to observe the universe and so this is the proof that it is fine-tuned for the possibility of our existence... because even if a few universal parameters were changed, the universe as we know it could not exist and we wouldn't be here to talk about it. Which strikes me as a bad case of mental masturbation: an activity providing momentary pleasure but that is ultimately sterile. It's very much like using Zeno's paradox to analyze real-life athletics. Doctor Pangloss would probably have subscribed to it, though: "It is clear, said he, that things cannot be otherwise than they are, for since everything is made to serve an end, everything necessarily serves the best end. Observe: noses were made to support spectacles, hence we have spectacles. Legs, as anyone can plainly see, were made to be breeched, and so we have breeches. . . . Consequently, those who say everything is well are uttering mere stupidities; they should say everything is for the best." (Voltaire, Candide).

Were we to change a few universal constants, our universe couldn't exist. Fine. If pi were to equal three (as in 1 Kings 7:23) instead of 3,1415926 and change, the ratio between a circle's diameter and its circumference would be different, something which would not be compatible with in our universe's geometry. But so what? A universe with different constants would, by definition, be a very different universe. We would probably not be there, but who's to say that a different universe couldn't exist instead? One with different laws, different types of energy and matter, perhaps different types of intelligence? The anthropic principle makes sense only if we centre things around our little selves, as we are wont to do. Let's look at things in a more humble way, and we might find that the universe isn't as it is so we can be there to observe it, but rather that we are here to observe it because the universe is as it is. We are the accident.

Friday, 25 April 2014

Meanwhile, the Nigerian prince...

Supplementary material

The 419 or Nigerian prince scam is one of the best known on the internet, and it apparently started before e-mails even existed. It comes nowadays in many iterations, but the gist of it is this: someone in a country far away needs your help to escape from unfair political persecution and is ready to share a vast fortune with you in exchange for a little help. All you have to do is send enough money to cover the person's air fare, as well as your bank account number so that the money can be transferred. (Sometimes true love is offered instead of the fortune, because the electronic correspondent has fallen madly in love with you after an exchange of three e-mails. You still have to send the air fare, though).

This is no mere prank, either: the people sending these e-mails are really out to get your money. Engaging in a discussion with them usually leads to a dead-end when you start asking questions, but people wishing to see how far the pirates are willing to go can get as far as be invited for a meeting in, say, the Netherlands. And they should bring money. It's pretty scary, actually!

Naturally, now that this scam is infamous the world over, a real Nigerian prince who genuinely needs help has better not trust to e-mail to ask for assistance!

Wednesday, 23 April 2014

A long and proud tradition!

Supplementary material

Jheronymus van Aken, better known today as Hieronymus Bosch was a Dutch painter from the late XVth-early XVIth century. He is famous for many striking paintings of hellish visions full of fabulous medieval beasts, nightmarish creatures, the grotesque fate of sinners in the afterworld and the like. These somber subjects are treated with a wonderful sense of creativity, an omnipresent sense of humour and more than a few hidden references! A serious analysis of Bosch's painting often reveals references to alchemical concepts or religious, social and political allegory.

The painting that gets our friend Bob all misty-eyed, up there, is called "the cure for folly"; it is currently in the museo del Prado in Madrid. It should be representing a doctor cutting out from his patient's head the stone that causes stupidity, but as is often the case in Bosch's work things aren't as simple as all that. First, I don't think anyone ever tried to make someone less stupid by removing rocks from their heads, although the device used in this image is appropriate for a late 1400's trepanation. We are therefore dealing in allegory: a learned person, or someone pretending to be learned, offers to improve a client's intelligence by some quick operation that does not involve any effort on their part. That the practitioner is a charlatan is made clear by his wearing a funnel for a hat: while the funnel is an appropriate tool in a scientist's laboratory, this is clearly not its intended use; like modern peddlers in "alternative" medecine, "alternative" science and "alternative" ways of knowledge, this person is wearing the trappings of a genuine scientists but doing it all wrong. He probably uses big scientific-sounding words too, in a haphazard and clueless way. Notice that what is extracted from the patient's head isn't even the purported stone of folly: it is actually a golden flower, which might represent whatever smarts the poor guy had to begin with. By trusting his fate to the skills of a charlatan, he has just given it all away.

Funnel hats were worn by other characters in Bosch's paintings, usually by doomed sinners, little demons or fraudsters. Funnel hats are today usually shown as appropriate headwear for crazy people, but it's difficult to say if that's as a result of their use in Bosch's work or as a popular tendency to put anything conical on the head of fools: dunce caps come to mind. (It may be stretching things a bit but a bishop also wears a conical hat called a mitre, and in the French language the chess piece we know as a bishop is called a "fou"... here a court jester, but the word also means "madman").

Bob's tin foil hat is not a funnel per se, despite its general shape (which also looks like a Hershey kiss). According to some conspiracy theorists, such an aluminum skullcap protects one from the government's mind-controlling microwave emitters, from aliens' telepathic probes, from mind-altering electromagnetic radiations and god knows what else. The origin of the concept is likely to be a 1927 science-fiction story ("the tissue-culture king") written by British biologist Julian Huxley, brother of Aldous Huxley (of Brave new world fame) and grandson to famous evolutionary biologist Thomas Henry Huxley, also known as Darwin's bulldog for his fierce defence of the theory of evolution during its first years.

The tin foil hat also gave us the funniest scene in M. Night Shyamalan's movie Signs.

Wednesday, 16 April 2014

Bullshit-flavoured yogurt

Supplementary material

There are keywords that the marketing industry just loves. These are words that inspire confidence or give a positive impression of the product they're associated with. "Fresh" is a term we encounter very often in conjunction with any foodstuff that doesn't come out of a can, even if it's a fruit that was picked weeks ago or a bag of chips that was forgotten in a corner after the zombie apocalypse. It just sounds good. (Like "crispy". "Crispy" always sounds good. There are even donuts named "Krispy Kreme", for crying out loud, because apparently even cream sounds better if it's crispy. And I must admit that "mushy-mushy cream" doesn't cut it). That's all fine, really; it's normal to say nice things about stuff you want to sell.

As soon as publicists come near anything having to do with health, though, our bullshit detector starts tingling. Understanding that we mere mortals tend to see the world in black and white, the marketing industry identifies words with a negative connotation (cholesterol! Booh! Hiss!) and others with a positive connotation (omega-3! Yay! Huzzah!) and starts using them whenever possible, even in situations where it makes little or no sense. It is not uncommon, for example, to see the virtues of orange juice exalted by making it clear, on the label, that it is "cholesterol-free". Which is true, by the way, but also an extremely odd thing to state since the only way to find cholesterol in an orange would be to add it artificially, something even the most evil of transnational conglomerates has not yet managed to do in a profitable way. Cholesterol-free bacon would mean something, but cholesterol-free celery, cholesterol-free rice or cholesterol-free water are just celery, rice and water. (I once saw candy advertised as being "fat-free", believe it or not, even though it was almost pure sugar and colouring. Oh, yes, that's definitely a healthy snack , right there! It's fat-free)!

I entertain this fantasy in which there is a secret hideout somewhere, probably buried deep under a dormant volcano, where little elves go through the scientific literature in search of a compound that could be turned into the next rising star of the marketing industry. Say, like omega-3 fatty acids. Most people are aware that a healthy diet goes hand in hand with a healthy life, but there is little profit to be made by telling people to maintain a balanced diet, eat some fish, not shy away from fruits and veggies and refrain from eating too much. It's just too simple. No, we must get hoi polloi to buy supplements! Don't tell them that a balanced diet is all they need, for that way lies the pauper house... if something in their diet is shown to be good (usually by showing that when it's not there, one gets sick) then get people to consume (and therefore buy) lots and lots of it! If they don't actually purchase five tons of dietary fibre each month, perhaps they'll at least associate "fibre" with "good" and will decide to buy this brand of pasta over that brand because it contains more fibre. With omega-3 fatty acids, studies show that a diet poor in this type of lipid correlates with a higher risk of cardiovascular disease. Clearly, that makes it a miracle product, akin to the blood in the Holy Grail or the potions of Panacea! Not only is a supplement of omega-3 fatty acids good for your heart, but it will also prevent you from getting cancer, will give your kids a higher I.Q., will prevent teen pregnancies, will prevent bad breath, will add three inches to your Johnson, will counter global warming, will enhance harmony between civilizations and may even delay the heat death of the universe. Yessir, ma'am! A great product, now on sale for a limited time!

One of the favourite fields of the nutriceutival industry is that of the immune system. Any good product, technique or fad worth its salt must, somehow, contribute to your immune health. I suspect that even a ciclosporin salesman could not afford to say their product represses the immune system; they'd have to say something like "reduces the chances of rejecting a graft". Which means the same thing, naturally, but in a more positive light. For customers, since we all know our immune system is what keeps the common cold at bay, "immune system" = "good".

The thing is that "stimulates the immune system", while sounding like a pretty positive thing, doesn't mean much when said put of context. It's as with the city's police: do we really want an overactive police force? Too many jaywalking tickets are not better than too few. The same goes for the immune system, which is, like a car, much more complex than one thinks under the hood.

The cells and the proteins involved in immune regulation have the ultimate goal (or function, say, since they don't have a goal per se) to maintain a balance between the cells belonging to our body and the rest of the universe that comes in contact with it. We do not want to allow other cells (bacteria, fungi, tiny animals) to reside within our bodies whenever they please, because apart from the yuck factor they are likely to cause the rest of our body to function at less than peak efficiency. Heck, they may even kill us if we let them. On the other hand, we cannot live in a bubble; we need to interact with the rest of the world without overreacting to its presence (which is basically what happens during an allergic reaction, which can lead to a lethal anaphylactic shock). Plus, we do need to tolerate the presence of all the micro-organisms that live on the surface of our body and on the surface of our gut; they help us keep other, more problematic, micro-organisms at bay and they help us do things like digest some material. Oh, and they make us fart. The world would be a sadder place without farts.

At the root of the immune system is the possibility of distinguishing between what is you (the self) and what is not you (the non-self). That is done via certain molecular marks mostly found at the surface of cells; these marks are called antigens. (These can shed and be found floating around, too; in fact, any structure that can be recognized by the immune system is an antigen). A certain type of immune cells called T lymphocytes, whose job it is to recognize antigens, learn early in our development to distinguish between the antigens of the self and those that do not. That way, during our entire life, they'll be able to float around our body and judge whether this or that antigen belongs here or whether it does not, thus triggering a response. This maturation is done in an organ that we lose in our teens, the thymus. (The thymus from veal is known as sweetbread, which is kind of odd. Why is sweetbread made of meat while sweetmeat is not?)

When bacteria manage to pierce the outer protective layers of our body and get into our system, their surface antigens will mark them as foreign bodies and we have several ways to dispose of them. Likewise, when a cell is invaded by a bacterium or by a virus, il will express at its surface foreign antigens that will mark it as an infected cell, and it, too, will be disposed of (because the immune system is a great believer in the scorched earth strategy). Helping in the process is a type of circulating proteins, called antibodies, that bind to antigens to signal their presence to other agents (like immune cells that will come to investigate, or like complement factors that will punch a whole in a cell membrane carrying a foreign antigen). So that we do not go overboard, our body also knows when to calm down its immune response.

As would be expected, like any system, this one has glitches. The immune response can be too weak, as is the case when we're immunosuppressed, and then pathogens can get the better of us; it can be unbalanced, as with an allergic reaction, where we react too strongly to something that's not that dangerous, or we can even see our immune system turn against our own antigens -a situation called autoimmunity. That last case is what comes to mind when some product claims to "boost" my immune response. Although I know that what's meant is basically "whatever's nice in your immune system, this yogurt/yeast extract/herbal tea will make nicer and ensure that you and the universe will live in harmony forever and ever and ever", what my brain imagines is that since I am not immunorepressed, a "boost" will mean a higher sensitivity to antigen; allergic reactions; rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes and multiple sclerosis. Which are, I'm sure you'll agree, far less marketable terms than "fresh taste".

Bah, let's be honest... there's no actual danger, here. The overinflated claims of these products are just empty words, like a fisherman's tale about the one that got away. But they do show that the industry never shies away from making outrageous scientific-sounding claims to get your attention, get your trust... and eventually get your money. Which is where it's at, in the final analysis.

Tuesday, 15 April 2014

Noah the undertaker

Supplementary material

For a hypothesis to be scientific and not simply a just-so story, it must meet certain criteria. Among these is falsifiability, or the possibility to be proven wrong. If an untestable hypothesis cannot be proven wrong, that doesn't make it right: it makes it useless. So the next time uncle Arthur tells you that you cannot prove that Leprechauns don't exist and that they're the reason thousands of unidentified people disappear each year, don't fret about it: the burden of the proof is on him, not on you.

Of course, in the case of a hypothesis that could be proven wrong but isn't, the lack of negative evidence (especially as the hypothesis or theory is tested again and again) makes one more and more confident that it is right.

A famous quote about the falsifiability of the theory of evolution is attributed to the famous biologist J.B.S. Haldane. Asked about what could convince him that the theory was wrong, Haldane answered "rabbits in the Precambrian". As we've mentioned before, the succeeding geological eras of our planet left layers of sedimentary rocks piled one over the other under our feet; these layers allow us to get a glimpse of what life looked like as we go farther and farther back in time (or deeper and deeper in the ground, which amounts to the same thing). An obvious testable prediction is that according to that theory, one should not encounter the remains of a life form in a layer that predates its apparition. During the Precambrian (anything older than 541 000 000 years BCE), we were still millions of years from the appearance of the first primitive fish, let alone amphibians, let alone reptiles, let alone mammal-like reptiles, let alone mammals, let alone rabbits. Were we to find fossilized rabbits among the remains of the Ediacara biota, it would fit with the theory like a square peg in a round hole. So there are ways to prove this theory wrong, and the fact that we can't is a pretty strong endorsement for its validity.

Needless to say, there aren't any rabbits in the Precambrian strata. That leaves creationists with a bit of a problem: how did fossils get organized in a way that somehow agrees with the theory of evolution? Hypotheses vary. Some claim that an evil imp organized fossils that way to confuse people. Some argue that as Noah's Flood struck, slower-moving animals like dinosaurs were drowned first and were the first to be buried under sediments. This is actually not an untestable hypothesis, unlike the first one, but it doesn't hold water (pun unintended). For one, the deeper strata do not contain the remains of dinosaurs, which appeared hundreds of millions of years after the Precambrian: they contain the remains of marine animals (no dinosaurs, no rabbits). Second, a large number of dinosaurs were not particularly slow-moving, judging from what biomechanics tell us about their skeletons. Third, according to this hypothesis, all slow-moving animals should be found in a deeper stratum than fast-moving ones; and yet, sloths are found just where the theory of evolution expects them: with other mammals, fast and slow, not with dinosaurs.

Friday, 11 April 2014

Red devil

Supplementary material

The fiendish-looking mollusc on the right is a Humboldt squid (Dosidicus gigas), also known as the red devil. It is a mean predator; swift, intelligent, curious, aggressive at times, and known on occasion to try yanking the mask and gear off scuba divers. A fascinating animal, no doubt, but not one I'd like to tangle with underwater.

Although its 5-foot length makes it a big bruiser, the Humboldt squid is not a giant squid (Architeuthis dux) nor a colossal squid (Mesonychoteuthis hamiltoni), both much larger, much heavier, and much less frequently seen.

Like most cephalopods, squids can project a cloud of ink from their anus to help them cover their escape from a predator. Therefore when a squid farts in an elevator, it can't pretend it didn't do it. He might as well have signed the deed.

The cuttlefish on the left also produces its own ink, which is sometimes used to colour pasta or rice in Spanish, Basque and Italian cuisine. The cuttlefish is however probably better known for its cuttlebone, which is no bone at all (since the animal is a mollusc). The cuttlebone is actually an internal calcium carbonate structure that, filled with gas, helps control the animal's buoyancy. Cuttlebones are omnipresent in bird cages, where they give the birds something to try their beak on and gives them plenty of calcium.

As for the contract that our ill-advised young cuttlefish is about to sign, it is of course a reference to the old German legend of Doctor Faust, a man who made a deal with the devil to gain knowledge, youth and plenty of sensual pleasure. The story's take-home message is that one should not favour earthly happiness over celestial rewards, since the latter are so superior in all ways (insofar as they exist at all, which has yet to be demonstrated in any way. Of course, meeting the devil face to face might have an effect on one's theological views).

The Faust legend has been adapted many times in literature, music, theater and the cinema. We really must mention Christopher Marlowe's late XVI century The Tragicall History of the Life and Death of Doctor Faustus, Goethe's early XIX century Faust: eine tragödie and Gounod's opera Faust, which gave Bianca Castafiore (the only recurring female character in the Adventures of Tintin series) the famous Jewel song.

Thursday, 10 April 2014

Real-life drama

I've seen this done, unfortunately. When I can, I advise the person not to be too hasty. The stress at the end of a long exam makes us take ill-advised decisions sometimes...

Wednesday, 9 April 2014

Ophthalmic distress

Supplementary material

Argus Panoptes is a giant from Greek mythology. His one hundred eyes made him a formidable guardian, especially as half of his eyes could stay awake while the other half slept. Accordingly, when a jealous Hera needed someone to stand watch over Io (a young nymph with whom a wayward Zeus had fallen in love and that he had changed into a heifer to protect her from his wife's anger, before having to surrender her as if she were an ordinary cow so as not to reveal the subterfuge*), she naturally turned to Argus.

Unfortunately, when Zeus decided to free his bovine paramour, he enlisted the aid of the god Hermes... and against a god, even a giant can not prevail.

Argus still gained a kind of immortality, as Hera rewarded his loyal services by making it so his eyes would now adorn the peacock's tail, where to this day they elicit our awe and amazement.

We have seen Argus before: here, here, and here.

* Shitty plan, I know.

Tuesday, 8 April 2014


Supplementary material

A creation of the British writer Arthur Henry Sarsfield Ward (better known as Sax Rohmer), Dr. Fu Manchu is one of the truly classic characters from popular literature, alongside Mowgli, Tarzan, Sherlock Holmes, Dracula and the Frankenstein monster. A scientific genius bent on world domination (aren't we all?), Dr. Fu Manchu has four doctorates; he has frequented the universities of Heidelberg, Edinburgh and the Sorbonne. That means he's bound to have published a lot of papers. An expert in poisons and murderous creatures of all kinds, I can imagine how he would deal with recalcitrant reviewers.

Monday, 7 April 2014


Supplementary material

As is the case for all vertebrates, the ancestors of today's mammals were jawed fishes (or Gnathostomata). Among these, some would one day use four of their fins like primitive legs to allow locomotion, and they would lead to the development of the tetrapods, or four-limbed animals. The gorgeous fossil Tiktaalik is an example of a fish with four rudimentary limbs; it is a perfect example of a transitory form between fishes and land animals. Tiktaalik's name come from Inuktitut since it was discovered in Nunavut; it means "burbot", a large freshwater fish that looks like cod. Please note that not all extant tetrapods actually have four limbs; some, like snakes, lost them along the way (but are descended from four-limbed animals).

Tetrapods include amphibians, reptiles and birds, as well as mammals; the amphibians were the first among them to walk the earth. A primitive trait among amphibians is that they still lay their eggs in water to keep them from dehydrating; this allows naturalists to group fishes and amphibians in one informal group called anamniotes. This distinguishes them from the later reptiles, birds and mammals who are collectively referred to as amniotes, animals that see their embryos develop in an amnios, a protective pouch found either in a solid egg that can be laid on land or in a uterus.

Early amphibians could get around on land, unlike their fish forebears, and some among them developed characteristics that would set them apart and allow the eventual appearance of reptiles. The amphibian Proterogyrinus is an example of such a proto-reptilian amphibian.

As reptiles diversified, they and their descendants accumulated differences that set them apart one from the other; they can be grouped according to the presence and/or position of certain skull cavities called fenestrae. We personally belong to the group called synapsids, defined by the presence of a temporal fenestra behind the eye, on the side of the skull. All mammals are synapsids, and the synapsid reptiles are now extinct so there's no way to get it wrong! The other reptiles still living today (and the birds!) are sauropsids, which can be further distinguished as anapsids (without a fenestra, and to which belong the turtles and tortoises) and as diapsids (all other extant reptiles as well as birds, with two fenestrae on the side of their skull, separated by the postorbital and squamosal bones. Dinosaurs were diapsids).

Perhaps you've once seen a reconstituted dimetrodon. This spectacular animal is often mistaken for a dinosaur because it is a very ancient reptile (it goes back to the Permian) but it is actually a synapsid, and therefore more closely related to mammals than it is to actual dinosaurs. Before mammals proper appeared, there were lots of such synapsids known as mammal-like reptiles.

The mammals that would evolve from mammal-like reptiles had new distinguishing features: they produced milk, they had hair, three auditory ossicles in the middle ear and a neocortex. They would then diverge along several ways, leaving us today with three types of mammals: the prototherians or monotremes, the metatherians or marsupials, and the eutherians or placentals.

Monotremes are mammals that still lay eggs, just as our reptilian forebears did. There aren't that many left today, and they're found only in Australia and New Guinea: all we have are four species of echidnas and the ever sympathetic duck-billed platypus, very likely my favourite animal of them all because it looks so unlikely. And it has a badass venomous ankle spur. Monotreme babies hatch out of an egg like reptiles but then rely on their mother's milk, which does not come out of a nipple but through pores in the skin.

Marsupials no longer lay eggs, but their embryonic development does not occur entirely in a uterus. The marsupial embryo comes out of its mother's womb after just a few weeks of gestation and crawls all the way to her abdominal pouch, where it will find a nipple to which it will stay attached as it finishes its development. Kangaroos, koalas and wombats are all marsupials. There are few marsupials outside of Australia and New Guinea; it seems that they fare poorly when having to compete with placentals. (Australia was already isolated from other land masses when placentals took over the rest of the world). The only marsupials left in America are a few types of opossums.

Placentals are the last mammals on the list; their embryos develop entirely in the mother's womb. They can be found pretty much everywhere on the planet.

The water opossum featured above, also called Chironectes minimus or yapok, is an American mammal with the great honour of being the only aquatic marsupial, and the dubious honour of being the only extant marsupial with a marsupial pouch in both males and females. Alas, the tasmanian tiger or thylacine (of which you can see an echo here), who also used to have a pouch in both males and females, was made forcibly extinct by man in the early XXth century. The last thylacine died in Hobart zoo, in Tasmania, in 1936.

Friday, 4 April 2014

There's actually nothing false in all this...

Supplementary material

A mole is more than an unwelcome visitor to our garden: it is also the number 6.02214129 × 1023. That power 23 up there means we could write it 602 214 129 000 000 000 000 000 if we had a big enough page.

Why is that number worth remembering? Because it is Avogadro's number, that's why, and Avogadro is one mean bastard who will break our legs if we show any disrespect to his number!!! No, I kid. It is worth remembering because it allows us to make a connection between the mass of a substance and the number of atoms it contains.

The periodic table of the elements classifies all known atoms according to the number of protons their nucleus contains, and it gives us the atomic mass of each. You'll notice that the mass given does not carry a unit: Oxygen, for example, has a mass of 15,9994. Sometimes we'll say it has a mass of 15,9994 Daltons. To connect those numbers to real life, we'll use Avogadro's number: in the case of oxygen, 6.02214129 × 1023 atoms weigh 15,9994 grams. Hydrogen has an atomic mass of about 1, meaning that 6.02214129 × 1023 atoms of hydrogen weigh 1 gram.

This concept explains what is the biggest problem with the homeopathic principle, which relies on great dilutions of certain substances to treat patients. Homeopathy is a therapeutic method invented by the German doctor Christian Friedrich Samuel Hahnemann in 1796, which by a funny coincidence is also the year Edward Jenner proceeded with the first vaccination. I find it amusing because both vaccination and homeopathy share at least one basic principle, in a sense: that of using like to fight like.

Past that one similarity, the big difference between them is that after two centuries, one has eliminated smallpox and pretty much made polio a forgotten nightmare, and the other works no better than any old placebo.

Vaccination relies on our adaptive immune system. Whenever we are exposed to a foreign substance of a certain size, one which does not belong in our body, certain specialized cells recognize it and try to get rid of it. This includes the molecules found on the surface of pathogens. How is this done? Partly through cells that specialize in identifying and swallowing foreign bodies; partly through cells that specialize in identifying other infected cells and destroying them, and partly through specialized cells that, once appraised to the presence of a specific foreign component in the body, produce proteins called antibodies that act as magic bullets that hunt it down and mark it for destruction. Oh, and once we've generated an immune reaction against something, there are cells that retain that information... if perchance we are exposed once again to the same pathogen, they'll allow us to generate such a quick response that we won't get ill again. We will be immune.

This system is actually quite powerful and can deal with pretty much any pathogen one can imagine, as long as we give it time to function. The reason we still get ill is that many pathogens evolved ways to circumvent our immune system's strategy (by hiding in certain places, for example, or by changing their molecular appearance very quickly)... and some pathogens are so damn efficient that by the time we raise a good immune response, we're dead.

Vaccination is based on the pre-emptive preparation of our immune system. It mimics an infection by using (a) more-or-less harmless pathogens that look so much like really bad ones that our system makes antibodies against both, as was the case with the vaccinia virus, far less dangerous than the smallpox virus; (b) attenuated pathogens, which have been modified in the lab so as not to cause disease (although immunosuppressed people can not use them); (c) subunits of pathogens, which are not dangerous on their own but teach our system to recognize the pathogens usually carrying them; and variations on these themes. The general idea is to expose the immune system to some part of a pathogen to give it a chance to recognize it later, without actually making us ill.

Homeopathy, meanwhile, relies on the philosophical principle of similarity; the same idea that gave us the expression "hair of the dog". Nowadays it mostly refers to the idea of drinking some alcohol to treat a hangover, but it comes from the suggestion to put some hair of the dog that bit you on the wound it left to help make it better. The idea is that when it is known that a substance can cause some disease in an otherwise healthy person, that substance (properly diluted) can be used to treat said disease in a patient.

Of course, presented like that, it could very well be that homeopathy is just vaccination under another guise: exposing the body to a small amount of a harmful agent, like a virus or a bacterium, or some other toxin. However, for the immune system to do its thing, it has to be exposed to at least a few molecules of a foreign origin... and homeopathic remedies are rather dilute. No, make that very dilute. Better yet, make that extremely dilute.

These remedies generally give you an idea of how dilute they are. A "1C" dilution, for example, means that whatever's considered has been diluted 100 times. A 6C dilution has been diluted 1012 times, or 1 part in 1 000 000 000 000. Where it gets silly is when we get to dilutions 12C and 14C, respectively one part in 1024 and in 1026... Since we exceed Avogadro's number, we don't even have one molecule of the original substance left.

Let's do a virtual experiment. Let's make a sucrose solution, which we can also call sugared water (although that sounds far less sciency)! Just so I don't seem to start with already diluted material, I'll put 40 packets of sugar in 1 litre of pure water. At 5 g per pack, it comes up to 200 g of sugar. It's not quite twice as sweet as Coca-cola, which contains 108 grams of sugar per litre, but I suppose we'll all agree that it is plenty sweet. Since we know that sucrose has the formula C12H22O11, we can look at the periodic table and determine that a molecule of sucrose weighs 342 Daltons, or 342 grams per mole. Our 200 grams here represent a fraction of that, or 0,585 mole; in terms of molecules, it comes up to 0,585 mole times 6.02214129 × 1023 molecules per mole, or 3,5× 1023 of sugar in our litre of water.

To make a 1C dilution of our sugared water, we'd need to take one part of it and mix it with 99 parts pure water. (It is said that homeopaths must mix stuff in a certain way for the remedy to work, and someone once amusingly said in the journal Nature that this must be how James Bond can tell that a vodka-martini has been shaken and not stirred). Such a 1:100 dilution would contain 3,5× 1023 / 100 molecules, or 3,5× 1021. That's still plenty sweet. But now let's look at the 12C dilution: 3,5× 1023 / 1024 leaves us with... 0,35 molecule! Less than one! Since we can not cut a molecule in two by diluting it, we either have one molecule left or none at all, with a 35% chance that we do. At the 13C dilution, 1 in 1026, we're down to 0,0035 molecule (or 3,5 chances in a thousand) that we still have a molecule in our container.

The dilution recommended by the good doctor Hahnemann is 30C, or 1 : 1060. In these conditions we'd have less than one chance in 100 000 000 000 000 000 000 000 000 000 000 000 to have even one molecule of sugar in our water. No, it won't taste very sweet. This is pure water. And that's not even the most dilute of homeopathic recipes! A popular remedy against flu called oscillococcinum is apparently prepared at a dilution of about 1 in 10400; as the initial material is duck liver, perhaps that's not such a bad thing.

Some fans of homeopathy refer to something called water memory to explain how infinitely diluted material might still work. In this model, water molecules could arrange in space so as to retain some structural information about past solutes. This hypothesis got a lot of momentum thanks to a controversial paper published in Nature in 1988 (with an odd advisory note by the publisher, saying in essence "I can find no fault with the technical aspects of this paper but I think it's wrong"); the experiments described therein could not be reproduced independently, nor when under the scrutiny of stage magician and pseudoscience debunker James Randi.

Wednesday, 2 April 2014

Misison Impossible

Supplementary material

It's true: dogs are colour blind. That doesn't mean they see in black and white, but that they can't distinguish red from green for lack of the proper photoreceptors. That is not a specifically canine problem, mind you: most mammals are in the same boat. We humans are very lucky to belong to the Old World primates category; thanks to a fortuitous mutation event described below, we gained an extra gene for colour perception that gives us trichromatic ("three colours") instead of dichromatic ("two colours") vision. And so we can better appreciate the work of Vincent van Gogh.

Light perception by the brain relies on the stimulation of certain nerve cells called photoreceptors located in the retina, acting as the film for the eye's camera. We have two main types of photoreceptors: they are called rods and cones, based on their shape, and despite a shared mechanism of action they have somewhat different roles. Photons must hit these photoreceptors for them to send the appropriate signal down a chain of nerve cells, and only certain wavelengths will do: we cannot, for example, see x-rays even if they are also part of the electromagnetic spectrum, just like visible light.

Here's how photoreceptors manage to convert photons into electric current that the brain can understand.

Each of these specialized cells contains a large stack of internal disks that form from folds in the plasma membrane. In cones, the folds remain connected to the plasma membrane but in rods they come loose inside the cell, forming what looks like a pile of pita bread. Each of these disks is studded with proteins called opsins. These proteins associate with a molecule called 11-cis retinal, which our body makes from vitamin A. That's why carrots are said to be good for our eyes, their bright orange colour revealing the presence of large amounts of beta-carotene, a vitamin A precursor.

In the rods, cells that allow us to see in dim light and are responsible for peripheral vision, the association between the opsin and the retinal is called rhodopsin. In the cones, cells that allow us to distinguish between colours, that association is called photopsin or iodopsin. The two types of photoreceptors are not distributed the same way in the retina: cones are less numerous (6-7 millions of them per eye) and are concentrated in a region of the eye called the macula, just opposing the pupil, while rods are more abundant (125 millions per eye) and cover a larger area, which also makes them responsible for our peripheral vision. That rods are more sensitive to light explains why a star seen from the corner of the eye at night seems to disappear when we try to focus on it: it's just not bright enough for the cones located at the back of the eye.

In the dark, each photoreceptor contains plenty of cyclic GMP, which by attaching to plasma membrane sodium channels allows Na+ ions to come and go, depolarizing the cell. This depolarization affects voltage-dependent calcium channels that also allow Ca2+ into the cell. This calcium causes the fusion of glutamate-containing vesicles with the plasma membrane, letting this neurotransmitter out, and when it contacts the glutamate receptors of the nearby bipolar cells it essentially tells the brain "I ain't seein' nuthin' at the moment".

When photons hit rhodopsin or photopsin, their energy is absorbed and induce a change in 11-cis retinal which adopts an all-trans conformation. This modification in turn activates a nearby G protein called transducin, which then triggers a phosphodiesterase. This enzyme turns cGMP into 5'-GMP, causing the sodium channels to close. The cell begins to hyperpolarize, the voltage-sentitive calcium channels close, and glutamate is no longer released. This interruption of the "nothing to report" signal is interpreted by the brain as "this photoreceptor has just been hit by photons!"

The opsin found in cones and in rods is not all the same. In fact, from what must have been some kind of ancestral opsin, successive events of gene duplication followed by sequence divergence has given the animal world access to a wide choice of different photosensitive proteins. The most useful property of all these proteins is that they do not have the same sensitivity to specific wavelengths, thus allowing us to tell the difference between a few of them (which we interpret as different colours).

The opsin called RHO is found in human rods. It is has an activation peak at 495 nm. Its gene is found on chromosome 3.

The cone opsins are the following:

  • OPN1SW, also called "blue opsin", covers a range from 400 to 500 nm with an excitation peak at 420 nm. Its gene is on chromosome 7.
  • OPN1MW, also called"green opsin", covers a ranbge from 450 to 630 nm with an excitation peak at 534 nm. Its gene is on the X chromosome, right after the gene for the red opsin. A small detail: in some people (who have a perfectly normal vision) this gene is repeated and there are two copies of the green opsin gene following the gene for the red one.
  • OPN1LW, also called the "red opsin", covers a range from 500 to 700 nm with an axcitation peak at 564nm. As we've just said, it is on the chromosome X, right before the gene for the green opsin.

Each cone expresses only one type of"coloured" opsin and will therefore specialize in a certain peak of excitability. There will be cones more easily triggered by red, blue or green wavelengths and it is the difference in relative stimulation among all our cones that tells the brain whether it's looking at something that's more blue, red or green. The rods, since they come in only one variety, only say "light". Because rods are lousy receptors for red light, since their excitability peak is sort of in the green, we can use a dim red light to preserve our night vision when we go out at night to observe the stars. The red light will not cause our rods to adapt to the presence of light.

As we've just mentioned, our different opsins come from the divergence of an ancestral gene. Looking at different branches of the tree of life we'll see how millions of years of evolution led to the development of several distinct opsins that give a wide range of colour perception. Chondricthyans, cartilaginous fish that include the sharks, the rays and the chimerae, rely on one rod opsin and four cone opsins: ultraviolet, red, green and blue. Bony fishes have even more, with one red, one ultraviolet, two blues and three greens on top of the rod opsin. Our own mammalian ancestors lost the green and blue opsins, leaving only the ultraviolet and the red opsin on top of the rod opsin; this may have happened due to a prolonged period of nocturnal lifestyle (and if I had to share the world with dinosaurs, I'd probably try to be as inconspicuous as possible, living in burrows and coming out only at night). What's the point of distinguishing many colours when you live in the dark, right?

"But", you'll ask, "what's this ultraviolet thing? I do see the colour blue, and I don't see the ultraviolet!" Which is perfectly true: our UV opsin has changed over time, and its peak excitability is now at a longer wavelength, giving us a "new" blue opsin. And that's where most mammals are today, including the dog, with a dichromatic vision. But we primates were pretty lucky: many of us evolved thrichromatic vision again. Our red opsin gene was duplicated on the X chromosome, and the new copy accumulated mutations that changed its peak excitability to a shorter wavelength, giving us a new green opsin. That happened to the ancestor of all Old World primates. When either the red gene or the green gene is mutated, we lose the ability to distinguish between red and green; this is a condition called daltonism. It's more frequent among boys than girls because the former only have one X chromosome and one inactive gene will do the trick; for a girl to be affected, both copies of the same gene would have to be affected (since she has two X chromosomes). Girls have a back-up, boys don't. That's only true for red-green colour blindness: the gene for our blue opsin is on chromosome 7, of which both boys and girls have two copies.

New world world monkeys can also be trichromatic, because some of their red alleles have mutated to get closer to green,which doesn't demand a lot of modifications, actually. Males can therefore have a red or green allele on their X chromosome, and although they'll still be dichromatic they won't be for the same reason as their neighbour. Some females will be lucky enough to have a green allele on one X and a red one on the other, and will have trichromatic vision (a great advantage to tell a ripe apple from a sour one). Howler monkeys (Alouatta and Aotus) are fully trichromatic: the green allele was translocated on the X, not far from the red allele, and so these monkeys are in a situation similar to ours (altgough they got there by a different way).