The evolution of caffeine

Let us turn now to the One True God of science and atheism, the Ground State of our existence. We shall now contemplate Caffeine. Raise your cup in praise.


This morning, as I was sipping the blessed stimulant and browsing the journals, I learned a little something. I learned how caffeine evolved, and it was both unsurprising and surprising. I am not a biochemist, so it’s always enlightening to read a little out of that field. This, for instance, is the chemical precursor in the synthesis of caffeine.


Oh, I said, I certainly do recognize that — I’ve been teaching budding cell biologists about important biological macromolecules for the past few weeks, and that’s a nucleoside. Note the ribose sugar with the attached nitrogenous base, the double ring of one pentagon attached to a hexagon? That’s xanthosine, which is also a precursor in the synthesis of those purines our cells use in signaling and assembling chains of nucleotides in DNA and RNA. That’s obvious. And then you look at caffeine, and it’s also obvious how cells make it: slap a couple of methyl groups (those -CH3s sprinkled around), and presto, you’ve got a happy drug. Easy.

Except…not all cells make significant amounts of caffeine. It takes specific enzymes to glue those methyl groups onto the core base with any reliable yield, and my cells might have xanthosine around, but they aren’t making any for me. I have to raid the vegetable kingdom and tear off their leaves and beans and hit them with boiling water to extract the blessed caffeine. And then not all plants make it — I can’t get a buzz on with a bowl of peas in the morning.

And then I learn that caffeine has evolved independently at least 5 times, and that the distribution of caffeine is patchy — some species in a genus will make it, while other related species in the same genus don’t. The caffeine molecule in Coffea (coffee) and Camellia (tea) and Theobroma is identical, but it’s synthesized by different pathways.

My mind is blown. Excuse me, but I have to take a break and think about this. I’m going to take a walk down to the coffee shop and gurgle down a couple of cups to help absorb this information. I’ll resume this post a little later.

You understand, don’t you? Go have another cup of coffee or tea while you’re waiting.

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WTF, New Scientist? WTF?

I guess New Scientist is feeling some heat over their disgraceful advocacy of Canavero’s ludicrous head transplant scheme. They just posted a rather defensive follow-up, and they’re still getting it all wrong.

It is one thing to find the science risibly weak, but on the bigger issue of head transplants – or more accurately, full-body transplants – nobody is laughing. The surgery seems macabre but is scientifically feasible and could offer real benefits to some people.

No. That’s the whole point. It is not feasible, no one is even close to being able to do it, and risibly weak is a ridiculous understatement. You can’t claim it’s feasible while also admitting that the science is weak. This makes no sense at all, especially considering how they close the thing.

Even if head transplants prove impossible or unacceptable, full spinal cord repair would be a breakthrough of huge importance. It’s time to get serious, lest this opportunity is lost.

It’s simultaneously feasible, but may also prove impossible? Who is writing this drivel?

No one is arguing about whether spinal cord repair would be a fantastically important advance. It would be. The point is, if you want to get serious about accomplishing that, you’re not going to get there by promoting an irresponsible hack like Canavero, or by touting nonexistent advances and bad papers as breakthroughs of huge importance.

At least Canavero isn’t comparing himself to Galileo yet

Just Frankenstein. Reader blf tracked down some information about Surgical Neurology International, where Canavero and his pals are having a grand time publishing shoddy science about head transplants. The journal has a complicated, messy history, with a mix of credible scientific papers and far-right-wing fringe conspiracy theories. That ought to make you question the source right there.

By the way, Canavero has a new paper there: HEAVEN: The Frankenstein effect.

The HEAVEN head transplant initiative needs human data concerning the acute restoration of motor transmission after application of fusogens to the severed cord in man. Data from two centuries ago prove that a fresh cadaver, after hanging or decapitation, can be mobilized by electrical stimulation for up to 3 hours. By administering spinal cord stimulation by applied paddles to the cord or transcranial magnetic stimulation to M1 and recording motor evoked potentials, it should be possible to test fusogens in fresh cadavers. Delayed neuronal death might be the neuropathological reason.

He sounds like he’d be fun at parties, doesn’t he?

I don’t get the point of this experiment. The question isn’t whether you can get an electrical current to jump the gap, crossing a lesion in the spinal cord; that’s trivial. The question is whether his fusogens promote active, specific regrowth of nerve fibers across the lesion, and you won’t get that by shocking corpses. It might have been an interesting observation 250 years ago when Luigi Galvani was shocking dead frogs, but it’s not something that needs to be tested now.

It’s also a rather pointless paper. He hasn’t done any of these experiments, but is just arguing that we should do them. Save that for the IRB. It shouldn’t count as a publication.

Your latest head transplant news

I’m sure you’re all wondering what’s happening with Sergio Canavero and his dangerous and unethical plan to transplant whole heads. Three new papers have been published claiming to have achieved partial regeneration of function of severed spinal cords in mice and rats and dogs.

Credible scientists do not believe it.

However, papers published today detailing the spinal cord repair technique applied to the dog have prompted other scientists to express concerns over the work. “These papers do not support moving forward in humans,” says Jerry Silver, a neuroscientist at Case Western Reserve University in Ohio.

Jerry Silver is so nice. I’m more likely to say that these are cases of scientific fraud and that they are so shoddily done that they shouldn’t have been published. Of course, the way that they got published is that Canavero was the editor of all three who allowed them into the journal.

The “breakthrough” that they’re promoting is that after severing the cords, they tried some additional experimental treatments that were supposed to promote regrowth: they injected the site with polyethylene glycol (PEG) and with graphene ribbons. I’ve used PEG to make hybridomas — it’s basically a membrane solvent that allows adjacent cells to fuse with one another. The graphene ribbons act as electrical conductors to allow current to flow across the lesion.

I gawp in astonishment that anyone would think this would work, and that any ethical review board would allow them to continue. I should belatedly warn you that the New Scientist link includes a video of dogs and mice intentionally crippled and struggling to move.

Here’s the problem restated in cruder terms. This is a fancy cable with multiple insulated strands running through it — of course, it’s nowhere near as complicated as the human spinal cord.

It’s cut.


Now a friendly electrician tells you he can fix it easily. He’s not going to splice each wire together to restore the proper connections, instead, he has an easier solution: he’s going to inject acid into the cable to dissolve insulation and encourage the copper wires to fuse, and he’s going to fill the cable with an electrically conductive goop that will allow signals to cross the broken end.

Does this sound like it will work to you? These are generic treatments that completely ignore the specificity of the necessary connections. He’s just claiming that anything to promote fusion will work, and that the cables will somehow sort themselves out.

Would you let him reassemble your home theater system with this technique? He’s happy to show you videos of his work, with a television flickering and fading and speakers sputtering and wowing, all for verisimilitude’s sake, but he’s not actually able to show you that these botched repair jobs used these techniques.

You might ask for some quantitative measures of the success of his technique, and he tells you that it works maybe half the time, and that all of the controls, in which he just cut cables and plugged them together, burst into flames and exploded. (of his experimental mice, 5/8 showed some degree of improvement, 3/8 died, and all of his controls died, which is really suspicious right there).

In another experiment with rats, all but one of the experimental animals was accidentally killed in a flood, but that one showed great improvement. One. This is nothing but a dubious anecdote. How could it get published at all?

Somehow, though, this shabby work is getting funded, is passing review boards, and is getting published. And Canavero is planning to try it on a human subject.

Apparently, if you put on a white coat and have a medical degree, you can get away with torturing small animals before planning the torture-murder of a human being.

“Psychologist finds humans fickle and shallow” is probably not a click-baity enough title

A lot of my balding friends are sharing this story (in jest, I hope) that claims Bald men are sexier, more masculine, scientific study finds

A recent scientific study found that men with bald heads are perceived to be more masculine, dominant and stronger. So if you are bald don’t worry, embrace it by shaving your hair off and whatever you do, according to the study, do not wear a toupee, comb over or try hiding your baldness.

Females will in general perceive men with a shaved head as more confident.

This is obviously a worthless study, for several reasons I will expand upon.

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You know that stupid story about inheriting your intelligence from your mother, that I debunked? Emily Willingham said pretty much the same thing, so now you can trust that I was right.

This is not surprising, and it didn’t require a conspiracy or telepathy or a Vulcan mind meld — it was a totally bogus claim that anyone with any significant biology training at all would have found mind-bogglingly inane.

In the same way, scientists around the world are groaning upon hearing Attenborough’s aquatic ape fannishness, and for the same reason — it’s patently false.

Say it ain’t so, Sir David


I’m sorry to report that Sir David Attenborough done screwed up. He is using his mellifluous voice and awesome reputation to promote the Wet Ape Theory. The show features all the usual suspects: recordings of Elaine Morgan insisting that her story is reasonable, Marc Verhaegen’s pseudoscientific hairsplitting, cartoon versions of evolution by Robert Ardrey and Desmond Morris, and that incessant nonsense of ignoring the whole organism and the existing evidence to argue that, well, this one little piece of our physiology could have evolved in the ocean, therefore we should claim that the whole beast was aquatic, because that is the only way they can now imagine it evolved.

The classic example is Alister Hardy’s initial hypothesis to explain why humans are hairless and have a layer of subcutaneous fat. What other animals have such a combination? Why, whales! They live in the ocean, and have lost most of their hair for better streamlining, and built up fat for insulation, therefore…humans lost their hair to better cut through the water, and evolved subcutaneous fat for heat retention. This is a bad hypothesis, because it ignores so much.

  • We don’t have any other streamlining adaptations, and are actually rather clumsy in the water.

  • Only aquatic mammals that live full time in the water show these adaptations; mammals that live part time in the water tend to have lots of hair.

  • Our “blubber” does a poor job of protecting us from that big heat sink, the ocean. We also lack the circulatory adaptations that make it useful in that function: countercurrent exchangers, arteriovenous anastomoses, that sort of thing.

  • Marine mammals have very little visceral fat; we’ve got loads of it. OK, I’ve got lots. Most of our fat is not distributed in a way to improve insulation.

And most annoyingly, the wet ape proponents simply pretend alternative explanations don’t exist. Hairlessness or reduced body hair, for instance, has evolved independently in several groups: cetaceans, naked mole rats, domesticated pigs, elephants, hippos, etc. So there are different strategies or environmental conditions that can lead to these features, and you can’t simply say all hairless mammals had to have gone through a dolphin-like evolutionary stage, because there are no other situations that can favor hairlessness.

But of course wet ape fanatics do — I’ve seen them seriously suggest that elephants had to have also gone through an aquatic phase.

Attenborough, I’m sorry to say, also takes this blinkered attitude. He closes episode 1 (there are two, I couldn’t bear to listen to the second) of his “waterside ape” series with what he proposes to be a “test” of the aquatic ape theory, which is no such thing. He claims to have new evidence: that there is a known feature of human infants which he predicts would be found in newborn cetaceans, and if confirmed, would both demonstrate the predictive power of the wet ape theory and provide an additional point of confirmation.

That feature is vernix, which is only known in humans. Vernix is the slimy, greasy coat that covers newborn humans, which he wants to claim is an aquatic adaptation, and therefore should be also found in other aquatic mammals. He is able to triumphantly announce that something similar has recently been reported in cetaceans.

But, again, the connection to an aquatic life has not been demonstrated. I don’t even see how vernix helps a mammal thrive in the water; it’s a fetal feature that is lost with the first bath, or is shed within a few days of birth. Vernix has many hypothesized functions for humans:

Vernix caseosa is a white, creamy, naturally occurring biofilm covering the skin of the fetus during the last trimester of pregnancy. Vernix coating on the neonatal skin protects the newborn skin and facilitates extra-uterine adaptation of skin in the first postnatal week if not washed away after birth. It consists of water-containing corneocytes embedded in a lipid matrix. The strategic location of the vernix on the fetal skin surface suggests participation in multiple overlapping functions required at birth, such as barrier to water loss, temperature regulation [the paper later shows a lack of support for this function –pzm], and innate immunity. Vernix seems to perform various integral roles during transition of the fetus from intra-uterine to extra-uterine life. It has also found various interesting diagnostic and prognostic implications in this arena. Thus, it continues to be an intriguing topic of interest among the medical fraternity to understand its detailed biology and function in the fetus and also to put its naturally endowed characteristics to use in the adult population.

Most of those multiple overlapping functions have nothing to do with adaptations for swimming — they are important for a mammal with no insulating layer of hair that is basically born prematurely with relatively few defenses. It is a logical error to imply that sharing a feature with many functions, like vernix, means that two species had to have had a similar ecological history. It makes no sense at all. I am very disappointed that David Attenborough has fallen for such crank nonsense.

I am not being peculiarly fussy, either. Very few people in the evolutionary/anthropological community think the Aquatic Ape is a credible hypothesis. Jim Moore has a very thorough compendium of rebuttals to the hodge-podge of contradictory details that make up the Aquatic Ape Theory; it’s a constant struggle to combat proponents who vomit up all kinds of odd scientific factlets that they claim are supportive of their cherished, much-loved, stupid theory. John Hawks explains why the AAT is pseudoscience. The Guardian has already posted a rejection of Attenborough’s “wishful thinking”. Alice Roberts quickly wrote an excellent response to Attenborough.

The original idea, and certainly Elaine Morgan’s elaboration of it, became an umbrella hypothesis or a “Theory of Everything”; both far too extravagant and too simple an explanation. It attempts to provide a single rationale for a huge range of adaptations – which we know arose at different times in the course of human evolution. Traits such as habitual bipedalism, big brains and language didn’t all appear at once – instead, their emergence is spread over millions of years. It’s nonsense to lump them all together as if they require a single explanation.

Despite the evidence stacked up against the theory, it is strangely tenacious. It has become very elastic, and its proponents will seize hold of any mentions of water, fish or shellfish in human evolution, and any archaeological sites found near coasts, rivers and lakes as supporting evidence. But we must always build our hypotheses on, and test them against, the hard evidence: the fossils, comparative anatomy and physiology, and genetics. In that test, the aquatic ape has failed – again and again.

It is a great shame the BBC recently indulged this implausible theory as it distracts from the emerging story of human evolution that is both more complex and more interesting. Because at the end of the day science is about evidence, not wishful thinking.

Unfortunately, I’m sure this bad idea will emerge again and again. There’s something appealing to the human psyche about one simple explanation of everything, even if that explanation is completely wrong.