History of the Unknown

A friend recently posted a BBC article about the difficulties of including the really important things in an overview of human history. And some of the facts in there, from a scientific standpoint, are fascinating.

First, there’s Fritz Haber, the man who (exaggeration for dramatic effect, now) taught us how to feed the world. By figuring out a way to artificially create ammonia from nitrogen and hydrogen, Haber led the way to mass-produced fertilizer and thus much greater crop production. Paradoxically — or ironically, I suppose — he was also vilified for helping to produce the gas that killed so many Jews during WW II.

There’s also a nice little shout-out to Ib Al-Haytham, whom historians consider the first “real” scientist, possibly predating people like Bacon or Galileo or, interestingly enough, Mary Somerville, one of Ada Lovelace’s tutors. Moving beyond theoretical, “natural philosophy”, Al-Haytham and others like him established the need for evidence which concurred with a scientific theory, and produced such detailed notes that other scientists would be able to reproduce their work much later.

Daily Roundup: From Ophthalmology to Oncology

Remember those vaguely annoying, slightly terrifying camera-looking things ophthalmologists use to check your eyes? For me, those were always a source of mingled fascination and terror; I kept imagining invisible beams of… something… piercing my eyes as I sat with chin wedged firmly into the machine.

Invisible beams of something they were — but it was simply light. Near-infrared light, to be precise, and doctors have been using this method, called optical coherence tomography (OCT), to see through the layers of the retina for a couple of decades. And now, researchers in Europe have come up with a way of scanning just beneath the surface of the skin to identify potential lesions and cancerous regions.

As the press release states, abnormal tissue in humans manifests itself in the blood vessel network as unusually large blood vessels, very close to the skin surface. The researchers surmise that the higher blood supply would be necessary for tumorous regions, which divide uncontrollably and need energy to sustain that level of cellular division.

The technique of OCT itself is pretty fascinating and there’s a high-level (at least, until the third paragraph) explanation at this site. It’s essentially ultrasound — but with light instead of sound waves. There’s a problem, however; light travels about 200,000 times faster than sound in tissue. If you were measuring how long it takes for the echo of the light to arrive back from the tissue, you would need electronic equipment with time resolution much more advanced than what’s currently available.

Enter the Michelson apparatus.

I must take yet another detour here and state that I think the Michelson-Morley experiment, which provides the scientific equipment for this group of researchers’ endeavors, is one of the most elegant experiments of all time.

At the time Michelson designed his experiment, the scientific world was engulfed with the question of the aether. If light wasn’t a particle (but was), and wasn’t a wave (but was), what was it? “What was doing the waving?” asks George Johnson, in his lovely book The Ten Most Beautiful Experiments.

It was theorized that an invisible, massless wind must be doing this blowing, and the physicists terms it the ether or aether. But if it were truly there, then it must be having an effect on things. For instance, light. Michelson reasoned that if he measured the “echo” from light traveling first with the aether, then crosswise against the aether, then he should see the difference in time between the echoes and therefore the speed of the aether itself.

Angling two sets of mirrors perpendicular and parallel to the theorized ether, Michelson was eventually able to determine that if there were an aether it was incredibly well hidden. In fact, there was no aether.

The OCT method is a rather nice vindication of this expensive, time-consuming, and by some accounts marriage-wrecking experiment. The interferometer concept is now used in probing the depths of our eyes to find imperfections, and if our research friends in Europe are right, then it will be invaluable in the early detection of cancerous regions as well.

Daily Roundup: The Fragility of Memory

When I read the EurekAlert about researchers at Northwestern Medicine who proved that “memory is like a telephone game”, I was a little puzzled. Even more so when I read the line “The Northwestern study is the first to show this.”

I’m a little confused because the first time I read of memory alteration, it was in a Wired article about the ultimate memory pill, which in turn references the work done by Karim Nader years ago. There’s a nice long article by Smithsonian.com which is essentially a profile of Nader’s life and work on this specific aspect.

The work by Northwestern is significantly different, though; for one, it’s conducted on human subjects and not on rats being taught aural cues. But while the Northwestern press release doesn’t refer to a theory of memory reconsolidation, Nader’s work and other research has much more background to support it. I’m not sure if this was simply not referenced in the press release, or if they genuinely were ignorant of the pre-existing work.

Either way, it’s heartening to see that the research is being replicated and the theory borne out by evidence: every time we remember something, at least part of our memory is being reconstructed from scratch. Our memories are never pristine and rarely reliable, which makes me wonder what research exists that compares the protein production of those with normal recall faculties to those with eidetic memory.

Daily Roundup: Neural Implants Help With Cognitive Function

Hot on the heels of the mixed press coverage of the ENCODE project is an EurekAlert article I’m very wary of taking seriously. Wake Forest University researchers claim to have created a prosthetic device that restores cognitive functions to primates whose capabilities have been impaired by injections of cocaine, in some cases to better than average.

Specifically, the monkeys involved were able to complete tasks correctly more often when they were stimulated by this prosthetic.

Before we begin talking about taking magic pills to help us in times of stressful decision making, let’s review the facts: the researchers set the monkeys to doing a task that involves matching a shape they’d seen a few minutes ago to an array of shapes, and they had been trained to achieve a 70-75% proficiency on this task for two years. Miracle cognitive therapy, this certainly isn’t.

But what I am interested in is how their prosthetic works. What are levels L2/3 and L5 of the brain and why are they important? How do they communicate, and why is that suppressed by cocaine (and why is dopamine involved in the first place?)

Most fascinatingly, how do you calculate the mathematical relationship between neuron levels? How is that even possible? And how do you tune a device like this to record during the correct input?

This, for me, is a classic example of a press release that promises so much and delivers tantalizingly little. Now I’m itching to speak to the scientists involved to ask them these questions.

Daily Roundup: Not Exactly Junk

It’s never been “junk” DNA. I seem to remember reading about this years ago, but it’s only made the news in a major way now, for some reason. Researchers working on the ENCODE project, which was begun to catalog all the pieces of the human genome — everything besides the genes themselves — have confirmed that about 80% of human DNA is regulatory in nature. That is, those bits of DNA don’t directly code for proteins that the body needs or uses.

As this Wired article puts it:

There are transcription factors, proteins that link these pieces together, orchestrating gene activity from moment to moment, and basic rules for that orchestration. There are also multiple layers of so-called epigenetic information, describing how the activity of genes is modulated, and how that varies in different types of cells.

And the proportion of these rules and regulatory elements to the actual genes themselves is quite stunning:

“Every gene is surrounded by an ocean of regulatory elements. They’re everywhere. There are only 25,000 genes, and probably more than 1 million regulatory elements,” said Job Dekker…

That’s a 40 to 1 ratio right there.

This information is crucial, because it’s often not enough to know simply which genes are expressed and which aren’t. Of course, the gene expression is often only the first step in a long process that results in a symptom or disease or hormone expression. But knowing only where the gene is and whether it’s turned on or off is akin to seeing only whether a a light switch has been thrown or not. You aren’t able to see the internal wiring or to control when and how that switch is thrown.

Hopefully, ENCODE will soon be able to give us glimpses of that wiring.

Daily Roundup: Introducing Pyruvate Kinase

One of the things that fascinates me the most is the sheer number of delicate, complex biochemical pathways that need to function in order to keep us in working order. Knocking out even one step — getting a protein fold wrong, transcribing a nucleotide base incorrectly — could mean disaster. It’s what leads to sickle cell anaemia, in which the haemoglobin in red blood cells are mis-formed and cannot bind with oxygen as efficiently as usual.

Sickle cell anaemia is caused by the mutation of just a single nucleotide. But there are other equally dramatic changes in the gene to protein pathway that can lead to complications.

One of these is Stanford’s recent research on muscle recovery using a “cooling glove”. It is, according to the researchers themselves, “better than steroids”; one of the scientists, a self-professed gym rat, improved his pull-up rate by 244% in 6 weeks.

The device itself is unremarkable: it’s a thing in the rough shape of a glove which creates a vacuum and draws blood to the palms. Plastic lining in the glove contains water, which cools the palms down.

Described by its own creators as “silly”, the glove works ridiculously well by taking advantage of two fundamental factors of body temperature. The first is the fact that most of the heat in our body is expelled through our face, feet and palms (mostly our palms) in much the same way that dogs expel heat through their tongues.

The second factor is linked to the reason why overheating in the body matters so much. Our bodies — and that of any other animal, really — run on proteins. Haemoglobin is one of these, but there are other, more subtle proteins that control the production of raw energy. The “unit” of energy that serves as a kind of energy currency is ATP, or adenosine triphosphate, which is required in any number of processes in the human body. But ATP and others in the protein family are held together by a delicate, temperature-sensitive balance of chemical bonds. Increase or decrease the ambient temperature too much, and the specific 3D structure of proteins can be critically damaged, depending on how sensitive they are to temperature.

And that’s exactly what happens when our bodies overheat. Muscle pyruvate kinase, or MPK, is responsible for the production of ATP within muscles. Much of the general population can rely on MPK working perfectly fine at any given time, but athletes, who train rigorously and ferociously, need all the help and recovery they can get between bouts of exercise. Overheating an athlete’s body means deforming and deactivating the MPK proteins within it, thus slowing down muscle recovery. But when the muscle cells are cooled down, MPK is basically “reset” and can begin working again.

It’s a beautiful, elegant system that the researchers took advantage of by simply applying the most efficient solution.

But pyruvate kinase’s role in human physiology doesn’t just stop there. MIT researchers discovered a far more crucial role that it could be playing in the production of tumorous growth.

Pyruvate kinase comes into the picture during glycolysis, which produces two molecules of ATP from a molecule of glucose. When one form of pyruvate kinase, called PKM1 is active all the time, the process goes on to produce much more ATP. Tumorous cells, however, express another form of the protein, PKM2, where secondary processes don’t produce as much ATP but go on to produce much more carbohydrates and lipids — essentially, the building blocks of cells. The idea seems to be that normal cells simply need more energy to conduct their normal processes, whereas cancerous cells require more raw material to continue to multiply. A previous study by the same team showed that turning on PKM1 activity in cancerous cells slowed tumorous growth.

What the team is trying to do now is more subtle: to force PKM2, the “abnormal” expression of pyruvate kinase, to operate all the time, “essentially turning it into PKM1”. I must admit I’m not sure how turning on PKM2 is equivalent to turning on PKM1, but in mice implanted with cancer cells and tested with pharmaceutical compounds that turned on PKM2 constantly, the researchers found no evidence of tumorous growth.

It’s pretty fascinating that a single protein is beginning to prove its worth in many ways. I’ll be interested to see what else pyruvate kinase can help with.

Daily Roundup: The Search for a Self

Blogger’s Note: written on Sunday; finished on posted on Wednesday, alas. 

Lazy Sunday mornings are the best times to feel contemplative and intellectual. Also, they are good for the eating of pancakes, but since my efforts to that end were thwarted today, I’m going to have to take the intellectual high road.

And rather easy that is, too. Last night I read an interesting piece on how complex a brain would have to be to exhibit self-awareness, and the answer seems to be, “not very”. Neuroimaging studies have apparently showed that the sense of self and identity arises, or at least registers, in the cerebral cortex, the most recognizable, wrinkly exterior of the brain. If that is indeed the case, it stands to reason that humans with severely damaged cortices would be unable to perceive themselves independently from others. However, experiments with subjects — both adults and children — showed that those with damaged cerebral cortices were still able to distinguish themselves from the rest of the world and recognize themselves in photographs and mirrors.

Ferris Jabr, author of this piece, is quick to point out the differences between self-awareness and consciousness. What I’ve described above is consciousness: the ability to perceive oneself. A more subtle step towards what I’ll call “personhood” is self-awareness, the ability to “realize you are a thinking being and think about your thoughts”, as Jabr puts it. Another way I’ve heard this described is meta-cognition, which is arguably a skill that dolphins and some apes share with humans (citation needed). For instance, if you were about to make a decision and then paused because you weren’t sure if you were making the right decision, you’ve been thinking about whether your choice is correct: i.e. metacognition.

Self-awareness and consciousness are the tools we’ll need to imbue robots with, if we’re talking about “real” artificial intelligence. Many AI machines and programs today have the capacity to do one task very well, or to learn from their environment and infer the details of their situation. But it has so far been impossible for them to recognize that they are separate entities in the world, and that their limbs and peripherals belong to them. I’m of that rather romantic camp (if there even is such a camp) which argues that AI isn’t “real” unless robots can interact with humans in a social context, as opposed to the idea that AI must simply be able to perform some probabilistic task, like making recommendations, booking reservations and answering questions posed in a more human format, much like the iPhone’s Siri. So when I read the news that Yale’s Nico robot could identify its limb in a mirror, I was a little excited.

First, though, I must dispel any notion that this is Skynet incarnate. As i09 points out (somewhat disgustedly), all the authors have done so far is to get Nico to identify its arm in a mirror as part of the 3D space, using its own reflection in a mirror. This is about as artificial as intelligence gets, because this doesn’t mean that the robot has any sense of self-awareness — it’s just learned to determine that its arm can have a 3D spatial coordination by “looking” at it. I’ll admit my excitement ultimately abated at this point. 

If you think about it, the really interesting problems are only beginning. A robot being able to recognize itself in a mirror still isn’t possible: for that to happen, I believe the robot would have to be given a command to activate something on its own body, based on what it’s seeing in a reflection. On second thought, that still might not prove anything, because the robot would be blindly following instructions to identify a point in space and then depress it. How would a robot be able to tell that something on its body belongs to itself?

I’d love to be able to speak to one of the authors about the assumptions they made and the next steps we should be taking if we want a truly self-aware robot.

Flipping through the comments section in Slashdot reveals a few more nuances that I wish the writers of the science pieces had thought to explore.

“Knowing what part of the camera scene is moving because something is happening, and knowing what part of the scene is moving because you’re waving your end-effector is useful. If you can extract your own state from indicators in the environment, then you have more information to work with…” says commentor Kell Bengal. It would’ve been nice to verify if this is really what happened with the authors.

Perhaps the “proper” test would be to get a robot to perform a task involving objects hidden from its direct sight, but visible from the mirror. This way, the robot would be able to move something around according to what the mirror is telling it, recognize that that movement is being done by itself, and modify its actions to suit the task at hand.