Wednesday, June 27, 2012

Science + Art at Artomatic

As much as I may complain about misrepresentations of literature in science or misrepresentation of science in entertainment, I love artwork inspired by science. Which is why I was delighted by the many science and art connections to be seen at Artomatic this year. 
(A very cellular scale) "Portrait of a Human" by Artologica
The work I was most excited to see was from Artologica. Michele Banks makes gorgeous water color paintings of neurons and microbes. I love how she brings out the natural beauty of bacteria. It reminds me how beautiful and sufficient the natural world is.

Another fantastic exhibit was by Sarah Noble, a research scientist at NASA and artist.

"Our Earth" Sarah Noble
She has some amazing portraits of planets and abstract rockets, but I really love her 'earth from space' series. Especially "our earth" shown above.  I love the stark whites, the hint of blue on the earth, and the feeling of loneliness it evokes. It reminds me of the scene in Ursula LeGuin's The Left Hand of Darkness, where two characters are traveling alone on a glacier which extends as far as the eye can see.

The 30 Computers Project uses discarded computer parts to make large 3D models of viruses and molecules and other exciting science things!
Adeno cd virus
You can go HERE to see how they made this large sculpture. 

Another favorite was Erika Rubel's Had Matter kitchen bugs: 
Kitchen Spatula Bug
These insects made with salvaged vintage kitchen utensils remind me of the little steampunk robots in Girl Genius. The only thing that could make them cooler is if they were controlled by rat neurons

Another delightful exhibit was from Duncan Guthery, quite possibly the coolest 11 year old ever.
He makes lego mosaics of familiar characters, like this streetfighter:
pixels made with legos

Also on exhibit were the Beatle's Yellow Submarine and a big Totoro. Not exactly science related, but turning legos into pixels is pretty cool.

And finally, the great Peep Diorama Contest submissions were all on display.  Although the "OccuPeepDC" diorama won the contest, my favorite was the peep CERN lab. 

Peep CERN lab
close up of marshmallow Peep CERN lab

There was so much more at Artomatic than I can possibly cover here. I was there for 4 hours or so and still only managed to see 3 of the 11 floors full to bursting of art exhibits. I am sure I missed some amazing science-related art. If you were there or are a science-related artist, please comment or email to let me know about your work. 

© TheCellularScale 
(I took all of the pictures here except "our earth" which I got from Sarah Noble's website)

Sunday, June 24, 2012

In defense of pink microscopes

I know I am late to the party here, as the "Science is a girl thing" video (embedded below) came out Friday and has already been ripped to shreds by many a blog. But I just couldn't stop thinking about it, so here's my opinion on that video and pinkifying science in general.

Hello Kitty Microscope
I am reminded of a quote from Pres. Obama's initial campaign.  He said (something like) "We need to shatter the blasphemy that says a black child with a book is acting white." 

It is equally true that "we need to shatter the blasphemy that says a woman in science is acting masculine."

Sometimes women in science dress down and wear less make up on purpose because they are worried that they won't be taken seriously if they look 'girlie' or even 'attractive'. Or specifically, "If I look like I took a long time doing my hair, nails, and make up, people might think I am not spending time doing science."

It is just as sexist to think that a woman wearing heels in the lab is less capable or less dedicated to science as it is to think that women shouldn't be in a lab in the first place. What a woman wears to the lab (within lab safety guidelines anyway) has NOTHING to do with how good she is at science or with how seriously she takes her work.  NOTHING.  The woman who wears heels and makeup, the woman who wears the same sweatpants 3 days in a row, and the woman who wears a t-shirt with jeans should all be taken equally seriously as scientists and judged on their work and not their appearance. 

Being 'masculine' does not help you be a better scientist and for crissake women, do not brag about having a 'masculine brain'. You are not helping inspire young girls to success when you attribute your intelligence and ability to being like a man.

I fully support feminine scientists and pink science equipment. There is no reason that a microscope shouldn't be pink and there is no reason that a girl shouldn't be able to have her own Computer Engineer Barbie if she wants one. 

Computational Neuroscientist Barbie

The message that you can both care about shoes and be a successful working scientist is important. It helps shatter the stereotype that scientific women are or should be masculine.

Recently a study by Betz and Sekaquaptewa (2012) investigated the influence of overtly feminine cues (such as pink clothes, makeup, etc) on middle-school girls' interest in math as a future career. They had the students read an magazine-style interview with a feminine woman (pictured as wearing make up and pink and described as liking fashion magazines), and a neutral woman (pictured with dark clothes and glasses and described as liking reading).

The finding that has been the focus of this paper's blog coverage is that for the girls that did not label math or science as their favorite subject, the feminine cues significantly reduced their self-reported interest in math as a career. They attribute this to the girls thinking that the feminine women are 'too good' and thus being discouraged because they don't see themselves as ever reaching those heights.

While this is an interesting hypothesis, a closer look at the study is merited.  First of all, there is not un-gendered control study. Might a similar effect might show up for middle school boys when shown either a muscular, athletic man who likes football or a neutral man who isn't particularly muscular, wears glasses and likes reading? This could be a general 'attractivity' thing where kids are intimidated by role models who 'have it all' or 'are too good'. Maybe it's not really a gender issue.

Secondly, what hasn't been discussed much is that 54% of the girls initially listed math or science as their favorite subject! And for those girls, the femininity of the woman in the article had no statistically significant effects on their interest in science and math. 

54% ! more than half of the girls in this study reported science, math, or both as their FAVORITE subject! and while there were no significant effects, there was a trend (p=0.19) toward the femininity of the role model increasing these girls' report of how 'attainable' both her femininity and scientific success might be.

Betz and Sekaquaptewa, 2012 Figure 3
This graph shows the "self-reported likelihood of attaining role model femininity and STEM (science, tech, engineering, and math) success" If anything the feminine role model slightly increased the attainability of these characteristics for girls who already like science (not significant, p=0.19).   

Regardless, I think the conclusion that feminine-looking science is bad for girls is not on sound footing. And again, I defend pink microscopes.

If you have already seen the It's a girl thing video, you might be now expecting me to support it.  But don't worry, I think it is as idiotic and every other scientist on the planet does. 

Far from showing feminine scientists, it is showing a scientist (the man) and separate from that a bunch of giggly girls dropping things. NOT HELPFUL. The only part I liked was the girl looking like she was concentrating and writing equations on the clear board. She looked feminine and pretty and she was 'doing' science.  If these girls had been actually doing science through the entire video (sitting at microscopes like the guy did, for example), I might actually have liked it.

The thing that is wrong with this video is not that these girls are wearing heels (though short skirts do violate lab safety codes), or that they look feminine or pretty. That's all fine. The problem is that they are not doing science, they are giggling and blowing kisses. If your goal is to combine femininity and prettiness with science, you have to COMBINE them, not present them as two completely separate things.

In conclusion, I'll leave you with one of the best comments so far: Cartomancer on Pharyngula suggests some equally stereotypical and offensive videos to promote diversity in science:

"67. cartomancer says:
I want to see what they’d come up with to get more LGBT people and ethnic minorities into science. “Science: it’s a gay thing!” featuring Abercrombie and Fitch models, bare-chested apart from an open lab coat, playing with unfeasibly suggestive phallic test tubes. Cut to discotheque-esque laser equipment and the word “science” with the C as a big rainbow.
Or how about “Science: it’s a black thing!” – grinding hip-hop beats accompanying blinged-up rapper types in pimped-out lab goggles, gold-rimmed petri dishes, Neil DeGrasse Tyson with a ridiculous posse behind him, research grants delivered in unmarked bills… yeah, you get the idea.
Well it amused me anyway."

© TheCellularScale

ResearchBlogging.orgDiana E. Betz, & Denise Sekaquaptewa (2012). My Fair Physicist? Feminine Math and Science Role Models Demotivate Young Girls Social Psychological and Personality Science DOI: 10.1177/1948550612440735

Thursday, June 21, 2012

Neuron-controlled robots: reverse-cyborgs

Last post we discussed robotically controlled biology.  In this post we will talk about biologically controlled robots.
The Hybrot: a rat neuron controlled robot
In 2001, S. Potter published a paper on the "Animat". A set of cultured neurons on a multi-electrode array (MEA, purple circle in above image) interfaced with a simulated robot.  That is, not a physical moving around robot as pictured above, but a computer program simulating what a robot/animal could do. 

They made a virtual room for the animat to 'explore'. (If you can make a virtual environment for a worm, I suppose you can make one for a petri dish of cultured neurons) The signal from the cultured neurons determined where the animat went. If one group of neurons fired, the animat moved left, if another group fired it moved forward, and so forth. (The actual equations translating neuronal activity to animat movement were more complex than this, but you get the idea.) 

So here's the really cool thing: When the animat 'hit a wall', a set of neurons were stimulated with an electric pulse. They also gave the cultured neurons a sort of vestibular system, stimulating a different area depending on which direction the Animat was traveling.

Although this Animat study was using a simulated environment and a simulated robot, using cultured neurons to control an actual robot was only a matter of time. 

Neurons are somehow even cooler when they are combined with robots, no?

So what I think is really exciting about this reverse-cyborg system is that you can study the formation of neuronal networks in response to realistic experience. The feedback system used in the Animat could reveal how natural synaptic plasticity and other network-forming processes could organize a set of neurons. I am particularly interested in the effects of neuromodulation on these neurons.  If they form a certain kind of network under normal conditions, how would that change if they were bathed in dopamine during the 'experience' or serotonin, or whatever. (Pick your favorite neurotransmitter).

It is easy to think that this robot has a 'brain' but really the cultured neurons are not organized like the brain at all.  Watching a network form in a dish is fascinating and can yield information about how neural networks form in general, but don't assume that this will tell us how networks actually form in an actual brain. 

Robots sure are cute (source)
These methods can be used to discover really interesting things about neurons and networks, but other kinds of study (such as ones using real, intact brains) are need to find out what actually happens.

© TheCellularScale
Demarse TB, Wagenaar DA, Blau AW, & Potter SM (2001). The Neurally Controlled Animat: Biological Brains Acting with Simulated Bodies. Autonomous robots, 11 (3), 305-310 PMID: 18584059

Sunday, June 17, 2012

Remote-controlled cyborg insects

Cyborgs capture the imagination. Whether human-machine prosthetics or machine-insect spybots, the possibilities for medical advances and for exciting sci-fi novels are virtually endless. 
Remote controlled beetle from 1909 from Insect Lab 
A paper in 2009 by Sato et al. made some significant advances in the frontier of remote-controlled cyborg beetles. Specifically they were able to stimulate relatively specific neurons in these beetles to get them to initiate flight, and then were able to control the trajectory of the flying beetle by stimulating the muscles on either side of the beetle. 

Sato et al., 2009 Figure 1B
The remote-controlled beetle had to be relatively large to hold all the machinery. With technological advances to make the system smaller and lighter, it is likely that smaller insects could be used.

So for all you paranoid people out there, don't worry, that tiny fly on your wall is not spying on you.  It's too small for that. If you see a gigantic green beetle on your wall, now that's a different story. But just so you don't rest too easy:

"As smaller and lower power microcontrollers and radios continue to appear on the market, researchers will be able to add an increasing amount of synthetic control into organic systems enabling new classes of programmable machines." Sato and Maharbiz, 2010
As you might imagine, this paper comes packed full with supplemental videos of beetles flying. The following video is Video number 1 of the Sato et al. (2009) supplementary videos, all 13 of them are available (open access) at the Frontiers journal website. This video shows the initiation and cessation of flight in response to positive or negative electric pulses.

And if you are more curious than freaked out by the possibility of remote-controlled bugs, you can make your own remote-controlled cockroach:

The same geniuses who brought you the spikerbox, also provide the "RoboRoach". The kit that you can buy from backyard brains provides everything (except the cockroach) to make a remote-controlled cockroach. This doesn't implant into its brain, only into its sensory antennae. And it doesn't make the cockroach fly.  It tricks the cockroach into thinking that it has touched something with its antennae, which makes it want to turn in the other direction. So even though it's not a super-spybot, it's as close as you can currently get to having your own cyborg pet.

Next post I'll discuss the opposite approach to cyborg techonolgy: Controlling robots with biological signals.

© TheCellularScale

ResearchBlogging.orgSato H, & Maharbiz MM (2010). Recent developments in the remote radio control of insect flight. Frontiers in neuroscience, 4 PMID: 21629761

Sato H, Berry CW, Peeri Y, Baghoomian E, Casey BE, Lavella G, Vandenbrooks JM, Harrison JF, & Maharbiz MM (2009). Remote radio control of insect flight. Frontiers in integrative neuroscience, 3 PMID: 20161808

Friday, June 15, 2012

Neurons are like Magnets

The earth has magnetic poles just like this magnet
It has long been thought that animals can use the earth's magnetic field to know where they are with respect to the planet itself. Migrating whales and turtles could use this method to determine which direction to swim, and pigeons could use this to navigate over long distances.
Loggerhead hatchling: brain still developing

Recently a paper out of Baylor college of medicine has shown the neural correlates which underlie this magnetic sense. They actually recorded from individual neurons while manipulating the surrounding magnetic field.

Specifically, Wu and Dickman (2012) recorded from electrodes implanted in the pigeon brain stem while the pigeon was sitting in a fully manipulable magnetic field. Wu and Dickman cancelled out the earths magnetic field and then applied a specific magnetic stimulation to the bird's head. After the last test stimulation, the brain stems were stained for c-fos. C-fos is an immediate early gene and is an indicator of activity in a neuron.  In other words the cells that show c-fos after stimulation are cells that were active during the stimulation. (For more on the use of immediate early genes see: erasing memories cell by cell.)
Wu and Dickman, 2012 Figure 2
They show the recording sites (red stars) and the c-fos positive neurons for all the pigeons in C. B is an example (dark dots are c-fos neurons). This brain stem diagram might look familiar, we've talked about the bird brain stem here before regarding sound localization. It seems that birds do a lot of spatial localization with their brain stem.

Wu and Dickman not only found that many neurons in this brain area expressed c-fos after magnetic stimulation, but they also recorded the actual spiking activity of these neurons during the magnetic stimulation.  They stimulated using small magnetic fields in the micro-tesla (uT) range.  For reference a typical MRI machine has a magnetic strength of 3 tesla or so (as in 3,000,000 uT).  They found 53 neurons in the recording area were sensitive to magnetic stimulation (but 276 were not), and that these neurons were sensitive to many types of signal modulation.

"We have shown that single vestibular brainstem neurons encode the direction, intensity, and polarity of an applied magnetic field...Our findings demonstrate that MR neurons are most sensitive within an intensity range that is naturally produced by Earth’s magnetic field, a necessary condition for a magnetoreception system to be useful in the derivation of geopositional information. However, Earth’s magnetic field varies over time (for instance, there has been a 35% decrease in its strength over the past 2000 years), so it would seem likely that magnetoreception systems adapt to the slowly changing fields through evolution and/or developmental plasticity in order to maximize magnetic sense perception." Wu and Dickman, 2012

This is an exciting paper that answers longstanding questions, but also raises new ones (as most exciting science does). For example, how is the magnetic field actually sensed by the pigeon? It is likely that these magnetic response (MR) neurons are receiving input from a sensory organ, and they probably wouldn't be magneto-sensitive on their own. Though an interesting experiment would be to culture these neurons (or the neurons of the putative magneto-sensory organ) and record their sensitivity to direct magnetic stimulation.

Darwin's pigeons
It would also be exciting to test changes in magnetic sensitivity of these neurons based on exposure.  If a pigeon is raised in a completely magnet-free area with the earth's magnetic field actively canceled out, would it lose its ability to detect the magnetic field? Or perhaps in that case, these neurons would become sensitized and respond more strongly to a magnetic stimulation. And how are these magneto-sensitive areas of the brain altered between bird species?  So many exciting questions!

© TheCellularScale

Wu LQ, & Dickman JD (2012). Neural correlates of a magnetic sense. Science (New York, N.Y.), 336 (6084), 1054-7 PMID: 22539554


Wednesday, June 13, 2012

A note about comments

I recently started moderating comments on this blog, but at the same time I changed something about my email notifications from blogger.  So long story short: while I was sitting around wondering why no one was commenting on my blog, a small trove of interesting, funny, and insightful comments was piling up behind an hidden email curtain. 

I have fixed this problem and published the comments.  Sorry about the delay, and rest assured that future comments will be moderated and published in a much more timely fashion. 

The Cellular Scale

Monday, June 11, 2012

Literature references in science: insightful or annoying?

"It is in our brains that the poppy is red, that the apple is odorous, that the skylark sings" -Oscar Wilde
(image source)

 I am pretty into literature, and I am generally in favor of art + science collaborations. I recently gushed about how cool it was that Aldous Huxley (famous author) was the half brother of Andrew Huxley (Nobel Prize winning neuroscientist). But honestly, I cringe almost every time I read a paper with "Proust" in the title. This is most likely because psychologists and neuroscientists tend to pick Proust and his Madeleine scene when they want to misrepresent some literature in a scientific context describe the idea that scent evokes memory.

(Madeleine recipe here)
In Swann's Way, Proust writes that as he savors the taste of the cookie dipped in tea, the memories of his childhood begin to take shape, like those little sponge things that are shaped like pills until you drop them in water and then they slowly morph into the shape of a triceratops. Or as he more elegantly states it:
"And as in the game wherein the Japanese amuse themselves by filling a porcelain bowl with water and steeping in it little pieces of paper which until then are without character or form, but, the moment they become wet, stretch and twist and take on colour and distinctive shape, become flowers or houses or people, solid and recognizable, so in that moment all the flowers in our garden and in M. Swann's park, and the water-lilies on the Vivonne and the good folk of the village and their little dwellings and the parish church and the whole of Combray and its surroundings, taking shape and solidity, sprang into being, town and gardens alike, from my cup of tea."  
-Marcel Proust, Swann's Way, In Search of Lost Time
While this is one beautiful passage among many in Swann's Way, it is not necessary for me to be a neuroscientist to enjoy it. Likewise, while it is a valid and interesting scientific question to ask "do odor and taste more strongly activate memories than vision, touch, or hearing?" It is not necessary to know that some guy wrote something about it sometime to understand the study or to understand why it is an interesting question.

Recently, scientists set out to study exactly this phenomenon.  Toffolo et al. (2012) constructed a study where people were put in a room with visual, auditory, and olfactory cues and watched a film.

One week later (hardly Proust's lengthy 'lost time') the same people were put back in the room with only one of the three cues, either visual, auditory, or olfactory.  They had the participants self report their memories of the film.  They found that the type of cue didn't make an enormous difference, but that odor cues enhanced the memory more than auditory cues, and the same amount as visual cues.

Toffolo et al., 2012 Figure 2
Interesting. Inconclusive.

But it's not only Proust, any famous author who has made an observation about how people sense things, or how ideas are in the brain not the world, or that we remember things a certain way can be the "basis" for a scientific study. Jane Austen, Virginia Woolf, Oscar Wilde, Emily Dickinson, Dante and James Joyce and many other literary legends have made statements that could be used or misused in a scientific context. But should they?

Here's the real issue. Does a literary quote within a scientific paper add anything to it? Does it make the science more accessible?
I am tempted to say no. I have yet to see a scientific paper using a literary quote in an insightful or helpful way. At best it is cute or entertaining. But at worst, it can be annoying, distracting, and misleading.

Is it only about accuracy? I feel the same way when science mis-interprets literature as I do when someone yells "The LTP has potentiated!" or other such science-sounding nonsense in a TV show. If you are going to use science jargon in fiction, it's best to get it as close to correct as possible.  (I give Dollhouse some points for effort for at least knowing that LTP is a thing, but minus points for not realizing that the "P" in "LTP" stands for potentiation)

And if you are going to use literary quotes in science, it's best if they actually have some relevance, and it's even better if you have actually read the book.

I truly love a good quote about human nature, or a beautiful poem about sensation vs. perception.
This poem certainly gives me a pulse of dopamine:

The Brain—is wider than the Sky—
For—put them side by side—
The one the other will contain
With ease—and You—beside—

The Brain is deeper than the sea—
For—hold them—Blue to Blue—
The one the other will absorb—
As Sponges—Buckets—do—

The Brain is just the weight of God—
For—Heft them—Pound for Pound—
And they will differ—if they do—
As Syllable from Sound—      
-Emily Dickinson

But, is it really better if we combine science and literature? They serve different purposes and I don't see the benefit of combining the two.  Particularly I don't see how the addition of literary quotes aids my understanding or interpretation of a scientific paper.

However, I am willing to be convinced otherwise.

© TheCellularScale

ResearchBlogging.orgToffolo MB, Smeets MA, & van den Hout MA (2012). Proust revisited: odours as triggers of aversive memories. Cognition & emotion, 26 (1), 83-92 PMID: 21547759

Here's a particularly cringe-inducing title:

Chu S, & Downes JJ (2002). Proust nose best: odors are better cues of autobiographical memory. Memory & cognition, 30 (4), 511-8 PMID: 12184552

Wednesday, June 6, 2012

What do mirror neurons look like?

You have probably heard about mirror neurons, but I bet you don't know what they look like. While we know exactly what Von Economo neurons look like, but know nothing about their activity patterns, the only thing we know about Mirror Neurons is their activity pattern.

Rene Magritte's Mirror (neuron)
Mirror neurons are the neurons in our brains that fire when we move a certain way and also fire when we see other people move in that same way. Exciting studies have shown that some mirror neurons are modulated by the specific intent of the action. That is a particular mirror neuron will fire strongly when a monkey picks up a piece of food to eat it, but fired less strongly when the monkey picks up the food to move it. The same neuron fired with the same intensity difference when the monkey watched someone pick up the food to eat it or pick up the food to move it. (reviewed in Casile et al., 2011)

Pretty exciting stuff, really. But what does it mean? There is some speculation that these neurons are essential for empathy, and for theory of mind. But the real question is even deeper than that.  What does it mean when a neuron fires in response to something (an animal, a motion). Does it mean that that particular neuron encodes that thing? Or does it just mean that that particular neuron is a part of a huge network in which gets activated in response to that thing?

If that single neuron were to die, would it affect your thoughts?

Forest for Trees
Or are there so many neurons activated in the network in response to something that one neuron dying would be like one tree falling in a forest?

Let's leave that question there for a moment.

Another, slightly more answerable question is: What do mirror neurons look like? They are often found in the motor cortex (area F5), but not all the neurons there have mirror properties. So which ones are mirror neurons? where do mirror neurons go? what is their chemical signature? Kraskov et al. (2009) have started to look at these qualities. They anti-dromically stimulated the neurons in F5 to determine if they went through the pyramidal tract or not (which would suggest that they lead to the spinal cord, though this is not certain).  They found that about a quarter of the neurons which follow this tract have mirror properties, and a quarter have anti-mirror properties (meaning they are active during the motion, but are drastically quieted during observation of the motion).  This in an interesting finding, and Kraskov et al. suggest that these anti-mirror neurons might serve to suppress actual motion while one is watching a motion.

Kraskov et al., figure 2 (mirror neuron activated on left, anti-mirror neuron suppressed on right)

In conclusion, some mirror neurons might send information to the spinal cord, but we still don't know how they are morphologically or chemically different from the (non-mirror) motor neurons right next to them.

I hope to soon see studies investigating the cellular, molecular, and physiological characteristics of mirror neurons. 

© TheCellularScale

ResearchBlogging.orgKraskov A, Dancause N, Quallo MM, Shepherd S, & Lemon RN (2009). Corticospinal neurons in macaque ventral premotor cortex with mirror properties: a potential mechanism for action suppression? Neuron, 64 (6), 922-30 PMID: 20064397

Casile A, Caggiano V, & Ferrari PF (2011). The mirror neuron system: a fresh view. The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry, 17 (5), 524-38 PMID: 21467305

Sunday, June 3, 2012

A Tale of Two Huxleys

Andrew Huxley is one of the founders of both modern electrophysiology and  computational neuroscience, and is consequently a personal hero of mine. His recent (May 30, 2012) death inspired me to learn more about his life.

Andrew Huxley (1917-2012)
Andrew Huxley along with Alan Hodgkin discovered the mechanisms which governed the action potential in nerve cells. They inserted micro-electrodes into the squid giant axon and recorded the sodium and potassium currents which generated and propagated the action potential. They shared the Nobel prize for physiology and medicine (with John Eccles) in 1963.

(squid giant axon)
Andrew Huxley is a hero of neuroscience because he (along with Alan Hodgkin) was not only able to develop the equipment and techniques necessary for the complex electrophysiological recordings of the squid axon, but he was also able to understand and mathematically interpret the results of their experiments. Hodgkin and Huxley's mathematical interpretation of their experimental results is basically the beginning of modern computational neuroscience. Their equations describing the flow of ions based on voltage and on concentration are still used in computational models of neurons today. Their famous series of papers (1952) in the Journal of Physiology culminates in their mathematical model of the action potential.

Time constants and steady state curves for activation and inactivation of sodium (Na) and potassium (K) channels (source)
This paper is fascinating to read because of the meticulous thought process that can be traced through it, and because of how much was not known about neurons at the time. The simple composition of the cell membrane was not clear and the fact that sodium and potassium ions actually flow in and out of channels formed by proteins was unknown.

"The next question to consider is how changes in the distribution of a charged particle might affect the ease with which sodium ions cross the membrane. Here we can do little more than reject a suggestion which formed the original basis of our experiments (Hodgkin, Huxley & Katz, 1949). According to this view, sodium ions do not cross the membrane in ionic form, but in combination with a lipoid soluble carrier which bears a large negative charge and which can combine with one sodium ion but no more. Since both combined and uncombined carrier molecules bear a negative charge they are attracted to the outside of the membrane in the resting state. Depolarization allows the carrier molecules to move, so that the sodium current increases and membrane potential is reduced. The steady state relation between sodium current and voltage could be calculated for this system and was found to agree reasonable with the observed curve at 0.2msec after the onset of a sudden depolarization. This was encouraging, but the analogy breaks down if it is pursued further. In the model the first effect of depolarization is a movement of negatively charged molecules from the outside to the inside of the membrane. This gives an initial outward current, and an inward current does not occur until combined carriers lose sodium to the internal solution and return to the outside of the membrane. In our original treatment the initial outward current was reduced to vanishingly small proportions by assuming a low density of carriers and a high rate of movement and combination. Since we now know that sodium current takes an appreciable time to reach its maximum, it is necessary to suppose that there are more carriers and that they react or move more slowly. This means that any inward current should be preceded by a large outward current. Our experiments show no sign of a component large enough to be consistent with the model. This invalidates the detailed mechanism assumed for the permeability change but it does not exclude the more general possibility that sodium ions cross the membrane in combination with the lipoid soluble carrier. " (Hodgkin &Huxley 1952) (emphasis mine)
They describe the ions being bound on one side of the membrane, carried through and released on the other side. If you did not have any idea about membrane channels, this would make sense. What is so beautiful about this is that their experiments and model constrain the vague theory.  However the ions get across the membrane, it must be this fast, this strong, and this dependent on temperature.
They continue:
                "A different form of hypothesis is to suppose that sodium movement depends on the distribution of charged particles which do not act as carriers in the usual sense, but which allow sodium to pass through the membrane when they occupy particular sites on the membrane. On this view the rate of movement of the activating particles determines the rate at which the sodium conductance approaches its maximum but has little effect on the magnitude of conductance. It is therefore reasonable to find that temperature has a large effect on the rate of rise of sodium conductance but a relatively small effect on its maximum value. In terms of this hypothesis one might explain the transient nature of the rise in sodium conductance by supposing that the activating particles undergo a chemical change after moving from the position which they occupy when the membrane potential is high. An alternative is to attribute the decline of sodium conductance to the relatively slow movement of another particle which blocks the flow of sodium ions when it reaches a certain position in the membrane." (Hodgkin &Huxley 1952) (emphasis mine)
Without any structural or molecular analysis of the membrane, Hodgkin and Huxley speculate that there might be sodium channels. They also discuss whether potassium has an entirely separate mechanism of membrane-transport, or whether it is the same one as sodium, but switched in affinity and timecourse in response to membrane depolarization.  Rather than quoting the entire paper here, I urge you to read it as an example of a truly beautiful train of scientific thought.

Aldous Huxley (1894-1963)

Speaking of truly beautiful trains of thought, a different Huxley, half brother to Andrew and 23 years his senior, was a world famous novelist. Aldous Huxley is known best for writing Brave New World, a dystopian novel about a 'perfect' future in which everyone has a place and likes it.
"Till at last the child's mind is these suggestions, and the sum of the suggestions is the child's mind. And not the child's mind only. The adult's mind too-all his life long. The mind that judges and desire and decides-made up of these suggestions. But all these suggestions are our suggestions... Suggestions from the State."
- Aldous Huxley, Brave New World, Ch. 2
Aldous Huxley was on track to become a scientist or doctor, but was struck by an illness which rendered him functionally blind for 3 years, preventing him from maintaining this course of study.

I am not sure which delights me more, that Aldous Huxley is a novelist with a scientist brother, or that Andrew Huxley is a scientist with a novelist brother.

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ResearchBlogging.orgHODGKIN AL, & HUXLEY AF (1952). A quantitative description of membrane current and its application to conduction and excitation in nerve. The Journal of physiology, 117 (4), 500-44 PMID: 12991237