Fundamentalist math: another outtake from the Science Cabaret

People are always inventing new ways to tell if someone is possessed by the devil. One way is to catch a grasshopper. We have a lot of them in Kansas. Catch one and count the legs. You count six? It says right there in the Bible that they only have four. Satan is a sneaky guy, always making your eyes play tricks on you. Six legs? Hah. Those huge dinosaur fossils? They’re not really there.

But these methods aren’t foolproof. When somebody looks at a grasshopper and counts six legs, maybe he’s just forgotten his reading glasses.

Counting legs requires some basic skills in math, which people generally learn in school, but a lot of fundamentalist Christians have decided to home-school their kids so they won’t learn a lot of liberal nonsense. In fact, some of these households promote a sort of Neo-fundamentalist version of creation which attempts to reconcile scientific discoveries with the Bible. Doing so requires an alternative form of math.

God obviously counts differently than human beings. For one thing, He really does know what number lies at the end of infinity. Our minds aren’t big enough. Think of the largest number you possibly can, you can still add 1 to it. Our brains just about get there, but we always fall a few numbers short.

God’s infinite Powers also give him the ability to bend time, and to change numbers to mean different numbers. One day a six will mean six, another day it will be 2πr.

Those seven days in the book of Genesis? Everything works out fine if each of those days lasted 500 million years. Years, on the other hand, were a lot shorter in Biblical times. Methuselah lived for 969 years? Without antibiotics? Come on. It’s obvious: One year for Methuselah was ten of ours. The dimensions of Noah’s ark? Just raise all those numbers to a higher power. An ark capable of holding all the species on Earth would have to be roughly the size of Texas.

So God counts things differently than people. Maybe what is 1 grasshopper leg for us is .6666 grasshopper legs for God.

In Kansas people use the grasshopper test to see if you’re possessed by the Devil. But in ancient times there were other tests. During the Middle Ages, for instance, there was the joke test.

The joke test arose from a huge theological debate. It probably started in a bar, as most of these things do. When people have one too many, or ten too many (another example of alternative counting systems), they get philosophical. Somebody says, I wonder if God has a sense of humor?

Back in the Middle Ages you couldn’t just let a comment like that go; you had to look into it. The debate over this issue became an awfully big deal. One faction said, God can’t have a sense of humor because what would he laugh at? He created EVERYTHING, and made it PERFECT. So he couldn’t have created something just to laugh at.

In the Medieval period they obviously didn’t know about the platypus. If Europeans had the platypus, which is obviously ridiculous, they would have known that God has a sense of humor. Why else would You create something that odd?

One faction of Christians had no sense of humor at all and so they decided that God couldn’t have one, either. That meant humor must have been invented by the devil, making it perfect material for a test. If somebody told a joke, you had grounds for burning them at the stake. Which is pretty funny if you think about it. Actually, it’s not funny. It’s ironic. Can God have a sense of irony? I’m not really asking. I don’t want to start something here, particularly if it will lead to a pile of wood and a book of matches.

Eventually the Middle Ages were over. People could finally giggle in public again, which required a new test to detect the presence of Satan. Some brilliant church committee came up with the water dunking test. If people suspected you of being a witch, they tied you to a board and dunked you in the river. After about two or three hours they brought you back up. If you survived they knew, Yup, that’s a witch. If you died… well, experiments sometimes produce negative results. But they’re hard to publish, so people kept using the method for a long time.

That test still exists, by the way, but today we call it the Guantanamo test.

The Renaissance saw the beginnings of modern science, which was pure atheism, so it provided lots of material for new tests. They took you out in the middle of a field and made you look at the sun. Tell us, they’d say, does the Sun revolve around the Earth or the Earth around the sun?

Since your life is at stake, it occurs to you that this might be a trick question. So you stall for time. You say, It depends – are we on Daylight Savings Time? In the process you become blind, but you don’t need eyes anyway. They just trick you all the time.

Even fundamentalist math won’t help you answer questions about planetary motion. That topic belongs to the domains of physics, and geometry, and so we’ll save it for another time.

American football, cheerleaders, and science communication

Recently I heard someone compare science communication to a sport. I didn’t catch which sport he meant, but he was fairly drunk, so it probably doesn’t matter. Maybe it was a dumb idea anyway, but there’s no law against metaphors. A metaphor is a way of saying one thing when you are thinking about something else, such as when you’re talking to your wife about the shopping list but your mind is actually entirely focused on your Facebook page. There are good metaphors and bad metaphors. For example, the upcoming visit of your mother-in-law could be compared to an inspection by a human rights organization, an invasion of kudsu, or a hostile takeover on Wall Street; one of these will fit your particular situation better than the others.

I do remember that the general topic of the conversation was differences between the way Americans and people from other countries communicate science. Now some people attribute this to the fact that a lot of American universities offer their scientists courses and workshops in writing and giving presentations. But the reality is, at an early stage in development, kids started playing different kinds of football. That causes fundamental changes in the way their neurons are wired. Then when you play football, you kill some neurons off again. But you kill off different ones. These changes in brain architecture spill over into other types of behavior, such as science communication.

American football is simple. One team has the ball, and it lines up against the other team. Then they crash into each other. When the dust clears, you look for the ball. Wherever it is, that’s where the teams line up to do it all over again. The goal is to carry it the ball over the goal line, but you have to be upright when you get there. So if the ball comes your way, look out, because everybody on the other team will try to break your legs.

If you make it to the End Zone, your team gets six points. I don’t know how they arrived at this number. One point ought to be fine, unless the total reflects some sort of risk factor. It’s true, for example, that your chances of reaching the End Zone alive are about one in six. But that wouldn’t explain why a shot in tennis can be worth 15 points, or the absurd scores you get for throwing a dart in a pub, unless there are a lot of dart fatalities they aren’t telling us about.

Anyway, American football teams have a sort of mascot called a coach, a combination of army drill sergeant and evangelist preacher who speaks in tongues, a genetic cross between a pit bull and a Neandertal, whose vocabulary consists of 100 words of which 90 are profanities, who has to be kept on a leash at games. Otherwise he will assault the referees, people in the stands, cameramen, or players from either team, sometimes biting them. This individual is usually a former football star who has been hit on the head so many times that he believes he is preparing troops for the invasion of Normandy, the defense of Stalingrad, or some other situation involving the fascist pursuit of world domination.

On your first day of practice, this coach takes you down to one end of the field and shows you where to stand. Then he puts his face 1cm from yours and gives you a whiff of breath that would permit you, if your football field is equipped with a mass spectrometer, to conduct a precise analysis of his diet and the metabolic status of various internal organs. But you wouldn’t have time because he immediately begins shouting in your face.

“You, scumbag!” he shouts.

“Yessir!” you scream.

“You see that goal down there?” he shouts.

“Yessir!”

“That there is our goal, and this here behind you is their goal.”

“Yessir!”

“You stand here and wait until the ball comes flying through the air. You catch it and you run straight for our goal, you hear?”

“Yessir!”

“If something gets in your way, just run over it! No matter what it is! If it’s somebody from the other team, run over him! If your grandma comes onto the field, run over her! If a 7-Tesla MRI scanner weighing about 6 tons suddenly drops out of the sky, just run over it!”

“Yessir!” you scream.

This all sounds simple enough. So you stand there a while and sure enough, here comes the ball. You catch it and all hell breaks lose. You run toward the goal and half the people on the field are trying to break your legs, whereas your teammates are trying to break the legs of the other team before they get to you. Beginners sometimes get disoriented and start running the wrong way. Then things really go wild: your own team starts chasing you while the other team tries to knock them down. If you switch and run backwards and forwards a few times in a row, the result is total anarchy. It’s like mixing up willy-nilly a bunch of promoters and inhibitors and glopping them onto cells. Both football players and biochemical pathways will get confused, sometimes at the same time, respectively. This state of chaos has one benefit: the person with the ball might slip through unnoticed. In some ways this resembles the way cancer cells evade the immune system, and in other ways it doesn’t. That’s completely irrelevant here, but I just thought I’d mention it.

Eventually an American football player gets hit on the head so many times that he forgets about the option of running backwards. It’s at this point that American football might be used as a metaphor for science communication. Just in case the topic ever comes up, for example in a bar.

Say you’re standing in front of an audience with some sort of scientific result in your hands. If we consider this information the ball, then the goal is to run it straight to the End Zone (into the minds of the audience), along the most direct route possible. If your path is blocked by some nuisance, like contradictory results, or mean comments from a reviewer, or a Coke can somebody put in your electron microscope, just push it out of the way, using brute force, a control experiment, or some sort of complicated explanation. Whatever happens, keep heading for the End Zone, and try not to get your legs broken along the way.

Now earlier I mentioned that there are good metaphors and bad metaphors. In Europe they play a different form of football, which ignorant people call soccer. A lot of people apparently use this game as a model for communicating science, which leads to a lot of games with no score.
I admit that I don’t completely understand the sport, but I’ve observed it a few times. It mainly involves a lot of guys standing around kicking a ball. They kick it forward and back, and left and right, unless a person from the other team is in the way, and then they kick him. This sort of aimless kicking usually goes on for about 20 or 30 minutes. At that point a member of your team says, Hey, look down there at the other end of the field. Somebody’s put up a net. I wonder if you could hit that with the ball? What would happen? Somebody tries it, and the whole stadium goes nuts.

I don’t know how many scientific talks you’ve been to, but I often feel like the speaker starts out in the backfield kicking a ball over here, and over there, sometimes getting in a few kicks on his competitors. If you get lucky, at some point the speaker discovers that there’s some sort of goal to aim for. If he hits it, usually by accident, everybody goes crazy.
Another reason European football isn’t a very apt metaphor is that there’s no good scientific equivalent for rowdy fanatics who get drunk, rush onto the field, and tear down the goalposts, unless you count behavior at scientific conferences. Incidentally, that’s the only context in which scientists typically switch jerseys. When you wake up in the hotel room of another person attending the conference, you might grab the wrong clothes.

This behavior is a little less common in American football. We have other nuisances to distract people from the game, but even they have parallels in science: cheerleaders (the reviewers who accepted your paper), marching bands (animated graphics in PowerPoint presentations), advertisements (funding from the pharmaceutical industry), and the emergency rescue teams that rush in to scrape people off the field (acknowledgements). Impact points clearly have a significance in American football. In that sport you do actually kick the ball sometimes, to get an extra point, which is like supplemental data. So it’s a complex metaphor. I’m not sure how helmets and faceguards fit in yet, but I’m working on it.

Juggling molecules while balancing the brain

Research highlight from the MDC
(visit www.mdc-berlin.de to see more highlights from MDC research)

People with a mental illness are sometimes described as being “unbalanced” or “having a screw loose.” These expressions may not be very polite, but they capture two important aspects of mental and physical health. First, organs such as the brain need to maintain an overall balance as we experience stress and engage in various types of activity. Ultimately this state depends on the functions of fundamental components in our cells – not screws, of course, but proteins and other molecules. A frenetic activity at this vastly smaller scale is required to ensure the stability of cells and tissues. While it is often extremely difficult to connect these levels of biological structure, the lab of Jochen Meier has established a new link. In a recent study in the Journal of Clinical Investigation, the group has connected a molecule called the glycine receptor (GlyR) to the operation of networks of neurons – and the way they are disrupted in epilepsy.

Jochen and his colleagues had already found an association between GlyR and brain disorders. They had carried out a molecular analysis of brain tissue from epilepsy patients. This disease is caused by an overexcitation of certain neurons, particularly in a region of the brain called the hippocampus. “We found that hippocampal cells produce unusually high proportions of a specific form of GlyR,” Jochen says. “The current project aimed to show how this molecule contributes to higher brain functions and eventually causes symptoms related to the disease.”

GlyR has one function that is clearly related to signal transmission between brain cells: it acts as a receptor for a neurotransmitter called glycine. Neurons release neurotransmitters into synapses, tiny gaps that separate them from their neighbors. These small molecules typically dock onto receptor proteins on other cells (postsynaptic) or on presynaptic receptors of the original cell. Depending on the type of neurotransmitter receptor and type of neuron, this either inhibits or promotes the signal.

The GlyR can be composed of two different proteins called alpha and beta subunits. Our genome encodes only one beta protein, but cells pick and choose between different genes for the alpha subunit. It may be combined with the beta subunit to create the GlyR; however, single cells sometimes produce GlyRs composed of alpha subunits only.

Like all proteins, the GlyR alpha3 subunit (GlyR-a3) is produced when the information in its gene is transcribed into an RNA molecule. Later the RNA is translated into protein. Along the way bits and pieces of the RNA may be removed in a process called splicing, creating proteins of different lengths, containing different functional modules – a bit like adding or removing wagons from a train.

GlyR-a3 RNA sometimes undergoes yet another change that affects its chemistry and functions. During a process called RNA editing, one letter of the molecule is swapped for another. This causes a corresponding change in the chemistry of GlyR-a3 protein and makes it work more efficiently. What Jochen’s team had discovered in epilepsy patients was an unusually high proportion of “long” spliced forms, and they also observed a swap in one letter of its chemical alphabet.

GlyR-a3 is known to inhibit the firing of neurons in the spinal cord, which can block the transmission of signals related to pain. This might mean that the form of GlyR-a3 found by Jochen’s team (the long spliced form, changed by RNA editing) was tuning down the excitability of neural networks in epileptic patients. To find out, the lab needed to observe the behavior of the altered molecule in an animal’s brain. Aline Winkelmann and other members of Jochen’s lab developed a strain of mouse in which particular cells in the hippocampus – called glutamatergic excitatory neurons – produce high amounts of this version of GlyR-a3.

Now they measured the way the change affected the animals in various ways: checking whether it affected the structure of neurons, the excitability of neural networks, cognition, memory, and mood-related behavior. Unexpectedly, they discovered that the altered form of GlyR-a3 caused an overexcitation of the system – and an important reason why.

“The long spliced form of GlyR-a3 is packed up with presynaptic vesicles,” Jochen says. “These are bubble-like packages that neurotransmitters are placed into before cells release them. Put this association together with an increased sensitivity to the neurotransmitter – and even some spontaneous activity due to the change in the receptor’s chemistry – and the neurons were prone to release more neurotransmitters. This had measurable effects on behavior: it disturbed the animals’ cognitive functions and some forms of memory.”

The study yielded another extremely interesting and wholly unexpected finding. The scientists discovered that in another type of cell, parvalbumin-positive inhibitory interneurons, higher amounts of the molecule had completely different effects on network excitability and behavior.
“Here the result was reduced network excitability, because it was enhancing the functions of this type of neuron,” Jochen says. “The change triggered anxiety-related behavior in the animals. But it did not cause any changes in cognitive function.”

A close scrutiny of the animals’ neurons and hippocampus didn’t reveal any significant changes in overall structure. In other words, higher amounts of this form of the GlyR-a3 molecule weren’t “rewiring” the animals’ brain network. Instead, they were persistently changing the overall balance of neural networks by enhancing the neuronal output.

“What we’ve done is to identify a mechanism at the level of molecules that is linked to the release of neurotransmitters and identifies two critical types of neurons that can cause an imbalance in the brain,” Jochen says. “We think this helps explain both changes in excitability of the brain network in epilepsy and the neuropsychiatric symptoms of some types of anxiety that are often associated with the disease.”

– Russ Hodge

Reference:

Winkelmann A, Maggio N, Eller J, Caliskan G, Semtner M, Häussler U, Jüttner R, Dugladze T, Smolinsky B, Kowalczyk S, Chronowska E, Schwarz G, Rathjen FG, Rechavi G, Haas CA, Kulik A, Gloveli T, Heinemann U, Meier JC. Changes in neural network homeostasis trigger neuropsychiatric symptoms. J Clin Invest. 2014 Feb 3;124(2):696-711.

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Ontogeny recapitulates sobriety:

From the Archaeal origins of life
to the pinnacle of evolution – a PhD

Some remarks made upon the award of the title Dr. to Dr. David Fournier

Considering the evolution of life on Earth, and the evolution of David Fournier in particular, aren’t you just smacked in the head by Haeckel’s famous principle, “Ontogeny recapitulates phylogeny”? Since that first twinkle in his father’s eye, well, actually since about four minutes after that first twinkle, David has passed through all the stages. He has made the transition from one-celled organism to undifferentiated clump of cells, worm, fish, tadpole, and rat, sometimes in the space of a single weekend. On another weekend David passed through the phases of Civil War reenactor, clownfish, and a member of the French Olympic curling team, but that’s another story. At every stage of his life, David has been curious. He was a curious tadpole. Among PhD students, he has a uniquely philosophical attitude; you can stop him on the street and discuss theories of the universe that turn out to be completely false, but are so elegantly constructed that it takes you a long time to figure that out. If you call David at three a.m. he will quote from the works of George Wilhelm Friedrich Hegel, with footnotes.

Anyway, if evolution were a ladder, which it is not, and don’t let anyone tell you otherwise, but if it were, David now stands at the summit. Along with other members of homo molecularbiologicus, and the even more highly developed member of its clade, homo bioinformaticus. The relationship between these species almost perfectly reflects that of Neandertals and modern humans. You may interpret that however you like.

After he passed through a pupal stage in school, David was squeezed by the French university system into a Wurst-like form, a saucisson, a sort of cocoon, sucking him in like a black hole in a box, although it is difficult to see how wormholes might fit into this analogy, unless it is a box of donuts. In any case, after many sleepless nights, David experienced some sort of cerebral event that made him run for ridiculously long distances, and if you stopped and offered him a ride, he’d say, “No, thank you very much.” Where I come from, you see a man running like that, he’s running away from something, but I didn’t see anybody behind him. Did David believe invisible people were chasing him? It’s not the kind of thing you can just come out and ask.

At some point David discovered the secret to success known to all graduate students: If you drink enough coffee, interspersed with a Red Bull every once in a while just for variety, the affinity between your conscious mind and body becomes very weak; they dissociate, and your mind drifts away. Your body becomes this robot that goes to work while your mind is sitting on a beach somewhere, sipping a margherita. Every once in a while a thought sort of floats into your consciousness. You say it out loud, and far away the robot body types it down and eventually you’ve collected enough strange and unrelated facts to make up a whole dissertation. You send the robot body to your thesis defense and it stands in front of your committee receiving signals from your mind, which is located on some remote planet. Every once in a while there’s a small interruption in the transmission and the robot suffers a blackout. You think aliens might be disrupting the signal. Or it might not be aliens. It could be other things, for example, coconut crabs. Somehow.

You remain in this dissociative state for three or four years before taking the next step of development and becoming a fully mature scientist with a PhD. Providing you don’t have any dangerous genetic defects, particularly monogenic traits like a cleft chin. If you do, you’ll develop along an alternative route. You may become an ice fisherman, or a garbage collector in Naples, or a person who carves butter into the shape of The Last Supper by Leonardo da Vinci.

But if everything goes normally, there you are, cruising down the hill in your doctoral cannister, becoming increasingly specialized, like a ball rolling down the Waddington model, except there’s nothing downhill at all about a PhD, it’s more like climbing up Mount Waddington, and free-climbing at that, without oxygen cannisters. Anyway, at some point a receptor on the surface of the container senses a molecule, probably a pheromone, and this triggers a massive epigenetic … well, let’s call it a process, I’m not a scientist, I don’t know the technical term for it. And I can’t say a lot more about it here, because it’s part of a massive secret international project called Systems Biology. This is so secret that even scientists don’t know what it really is. No one has the complete picture. It’s been split it up into little parts and each person is given just a little piece to work on. You feel like you’re some little part of a big network, and you’re not even a very interesting part, like a diode, or a RAM, or beta-catenin. We suspect it is a huge conspiracy. I probably shouldn’t be telling you this.

This epigentic event comes right at the conclusion of your PhD and it’s like setting off some sort of developmental IED, a roadside bomb filled with shrapnel. The shrapnel are microRNAs. They fly around everywhere and derepress a pathway involving canonical Wnt signaling, or non-canonical Wnt signaling, or some other type of Wnt signaling, simultaneously or in various combinations, and as a result we have 393, 217, or 655 potential new targets for cancer research, respectively.

microRNAs are so dangerous that any cell that sets them off would have to be an idiot, because that cell is always the first to get blown to pieces. Of course, your average cell is not generally noted for its intelligence, even though its DNA might encode a complete play by William Shakespeare. You can also inscribe Shakespeare onto a grain of rice, but that doesn’t make the rice smart, despite its massive genome, which is many times larger than that of humans. No, the true sign of intelligence is to learn from your mistakes, but if you mess around with microRNAs you won’t learn anything at all, because you’ll undergo apoptosis. Letting microRNAs loose is like putting a bunch of cats and raccoons together in a cage. You might do it once, but you certainly wouldn’t climb in with them. It’s not a pretty sight.

Now for several paragraphs this piece has been headed for a point, but then it got sidetracked during a long metaphor, like meeting a woman in a bar, and then walking her home, and I won’t go into detail about what comes next, we’ll just take a little pause at this moment so that each of you can individually complete that scenario using your own imagination.

The real point is that with the award of his PhD, David Fournier has reached scientific maturity. It’s like puberty, it’s like a butterfly, two concepts which can never be combined in one sentence without sounding creepy. Yes, even if we’re talking about reaching puberty in a metaphorical, scientific type of way, some people will automatically think of sex. Especially mentally disturbed people. If you’re thinking about sex now, you should stop, and perhaps consult a psychiatrist. And last but not least (not really, but it just felt like time to throw in a common but meaningless transition device), if you started reading this piece thinking that it would contain a discussion of David’s sexual phenotype, you can think again. This is not that type of magazine.

* * * *

So here David Fournier stands at the summit of human evolution, and at the peak of his maturity, both scientific and sexual, and he’s wearing a funny hat. For just a brief moment, he feels immortal. And then he is struck by a vision, that moment of clarity that comes to everyone upon reaching the top of a ladder: the realization that there’s only one way to go from here. At some point on the way down he’ll discover Viagra, which is a mixed blessing. It improves your potency but tends to have the opposite effect on a scientific career.

Sure, you hear these rumors about guys going on to become professors, but where’s the evidence? Professors are supposed to be in their lab, or a classroom, or in their office, but when you go looking for them, they’re never there. That calls to mind something David read while doing research for his dissertation. He found a quote from the great Ernst Haeckel, who had some not-very-nice things to say about professors before becoming one himself:

Es ist eigentümlich, daß sich gerade diejenigen Professoren am meisten gegen die Abstammung vom Affen sträuben, die sich bezüglich ihrer Gehirnentwicklung am wenigsten von demselben entfernt haben.

Now David’s knowledge of German is somewhat limited, restricted exclusively to the works of Hegel, who was really French (on his mother’s side; they pronounce the name Hégelle), so I have thoughtfully provided a rather loose translation into English:

It is appropriate that those professors are the sharpest critics of the idea of the descent of man whose brains have evolved least since the apes.

David actually put this quote into his dissertation, deep in the discussion, sort of a test to make sure the committee actually read the thing, like putting a jalapeno in a piece of pie. In English the quote comes out sounding a little mean, a little superficial, completely lacking the gravitas and resonance of the German original. When my own writing suffers from these problems, often right after lunch, I run it through Google translate and see if it doesn’t sound better in some other language. Here’s the quote in Basque:

Bitxia da, hain zuzen, tximinoak jaitsiera aurka gehienek badakite irakasleek, gutxiago ikusten duten hori kendu garunaren bera garapenean.

That automatically adds some intellectual depth, because you have to be a genius to learn Basque. I can’t provide a literal translation, but when you hear it out loud it sounds terribly dark and mournful. You automatically sense that it’s talking about death: either that of the professor, or the ape, and whichever one is left is throwing a wake for the one that died. Indisputably, the best wakes are thrown by the Irish, so here’s the Gaelic version, in the form of a toast delivered in a pub:

Tá fiosracht, i gcoinne pheaca, mar shiombail de na múinteoirí, ina choinne aon.

The first time David ever heard this, he thought it was French, and I won’t tell you what he thought he heard, because in French this sounds incredibly obscene. I thought the person was speaking English, perhaps with an Italian accent, and I heard this:

Gee I feels wrecked. I’m gonna puke marshmellows in a minute onna your chinna, hon.

But that’s just ridiculous. In Irish it’s a lot better; after a literal translation back into English you get this:

Curiosity is against sin, as a symbol of the teachers, against any.

This statement has an aura of mystery, like a Zen koan, or a Communist slogan, or the kind of thing a cabdriver would say to you. Probably a foreign cabdriver, for instance someone from Belgium.

* * * *

Successfully completing his doctorate required that David learn the Secret Formula for Success in a PhD, which can be purchased on-line, providing no one has hacked your PayPal account. The program guarantees success if you buy it, rather than downloading the bootleg copy, as David did, and then religiously follow all 12 steps. It’s true that 12-step programs have become popular in many scientific fields, such as Alcoholics Anonymous, and astrology, but any similarities between their lists and this one is just one of those bizarre coincidences that sometimes happen when you live in a random, chaotic universe.

1. We admitted we were powerless over science—that our lives had become unmanageable.
2. Came to believe that a power greater than ourselves (our group leader) could restore us to sanity, despite having no good reason for believing this.
3. Made a decision to turn our will and our lives over to the care of God (our group leader) as we understood Him.
4. Made a searching and fearless moral inventory of ourselves, our lab benches, and the bottom drawer where He keeps the emergency bottle.
5. Admitted to God (our group leader), to ourselves, and to another human being, for example, a postdoc, or our psychiatrist, or just some random person in the street, the exact nature of the mistakes we made in our experiments.
6. Were entirely ready to have God (our group leader) remove all these defects of character, using only a pipette and many cover slips.
7. Humbly asked Him to remove our shortcomings, by docking our pay, or making us clean out the mouse cages.
8. Made a list of all persons whose experiments we had ruined, and offered to repeat them all, on weekends, in exchange for authorship somewhere deep in the middle of the list.
9. Made direct amends to our competitors wherever possible, except when to do so would injure them or others, unless we would get more impact points by sticking it to them.
10. Continued to take personal inventory, and when we were wrong, promptly admitted it, preferably before the paper had been submitted, in which case we snuck it in during the review process.
11. Sought through prayer and meditation and incredible amounts of caffeine and late-night phone calls to improve our conscious contact with God (our group leader) as we understood Him, praying only for knowledge of His will for us, hopefully sent by email, and the power to carry that out if we have high-throughput technology platforms and if we feel like it.
12. Having had a spiritual awakening as the result of these steps, we tried to carry this message to the next generation of predocs, by making their lives just as miserable as our had been, and to practice these principles in all our affairs.

The twelfth step is hardest, especially if you have a minor genetic defect like a conscience, or a soul, and only a few truly master it. Which way will David’s ball roll? At what point will he reach his finally differentiated form? Will fundamental discoveries in stem cell research permit him to de-differentiate if he decides, at the age of 70, to start a new career playing the pan-pipe with a band of South American street musicians? Will he ascend to the Académie Française, and then be buried alongside Voltaire in the Panthéon in Paris, after they remove his heart and brain, as they did with Voltaire? Or will he end up under a parking garage in England, like Richard III? Only the future will tell. Further research is necessary. Although we do have some promising lead compounds.

– Russ Hodge

Mating with Neanderthals

Today, April 1, Nature Communications reports on another study on those sneaky Neanderthal genes that crept into the modern human genome, probably by climbing up a tree in the yard and entering through a bedroom window. In a popular article describing the project, Emily Willingham writes:

…Khrameeva and her colleagues noted that speculation regarding some Neanderthal-H. sapiens gene flow through sexual reproduction is “appealing.” And experts in the field generally agree that the idea is plausible, even if it’s not their favored explanation.

Now most Homo sapiens wouldn’t consider mating with a Neanderthal very appealing, but we do have to consider that about 4% of our genome derives from Neanderthals, so I’m guessing about it appeals to about 4% of the population. Since some governments are considering expanding the definition of marriage to include relationships with other species, at least when submitting their tax returns, it’s time for this minority to speak up and be heard.