Saturday, March 25, 2017

138. Good prions


Previous - 137. Proust!


Proust continued

Sentimental Proteins
p93 [This section covers the search for how the brain stores memories. The author focuses on the work of Dr. Kausik Si and Eric Kandel. They focus on a molecule called CPEB with an unusually repetitive amino acid sequence.]
Immediately, Si began looking for other molecules with similar odd repetitions. In the process, he stumbled into one of the most controversial areas of biology. He found what looked like a prion.

Prions were once regarded as the nasty pathogens of a tribe of the worst diseases on earth: mad cow disease, fatal familial insomnia... [which we've read about] and a host of other neurodegenerative diseases. Prions are still guilty of causing these horrific deaths. But biologists are also beginning to realize that prions are everywhere. Prions are roughly defined as a class of proteins that can exist in two functionally distinct states (every other protein has only one natural state). One of these states is active and one is inactive. Furthermore, prions can switch states (turn themselves on and off) without changing DNA. And once a prion is turned on, it can transmit its new, infections structure to neighboring cells with no actual transfer of genetic material.


In other words, prions violate most of biology's sacred rules. They are one of those annoying reminders of how much we don't know. Nevertheless, prions in the brain probably hold the key to changing our scientific view of memory. Not only is the CPEB protein sturdy enough to resist the effects of the clock -- prions are famous for being virtually indestructible -- but it displays an astonishing amount of plasticity. Free from a genetic substrate, CPEB prions are able to change their shapes with relative ease, creating or erasing a memory. Stimulation with serotonin or dopamine, two neurotransmitters that are released by neurons when you think, changes the very structure of CPEB, switching the protein into its active state.


p94 After CPEB is activated, it marks a specific dendritic branch as a memory. In its new conformation, it can recruit the requisite mRNA needed to maintain long-term remembrance. No further stimulation or genetic alteration is required. The protein will patently wait, quietly loitering in your synapses... It is only when the cookie is dipped in the tea, when the memory is summoned to the shimmering surface, that CPEB comes alive again. The taste of the cookie triggers a rush of new neurotransmitters to the neurons representing Combray, and, if a certain tipping point is reached, the activated CPEB infects its neighboring dendrites. From this cellular shudder, the memory is born.


...Every time we conjure up our pasts, the branches of our recollections become malleable again. While the prions that mark our memories are virtually immortal, their dendritic details are always being altered, shuttling between the poles of remembering and forgetting... [I wonder if there's anything about a near-death experience that triggers this system?]


...Swiss scientists... have... discovered a link between the prion gene that causes mad cow disease and increased long -term memory. Essentially, the more likely your neurons are to form misfolded prions, the better your memory is...


...experiments show that the [CPEB] protein can become active for no real reason, since its transformation is largely dictated by the inscrutable laws of protein folding and stoichiometry. Like memory itself, CPEB delights in its contingency.


This indeterminacy is part of CPEB's design. For a protein, prions are uniquely liberated. They are able to ignore everything from the instructions of our DNA to the life cycles of our cells. Though they exist inside us, they are ultimately apart from us, obeying rules of their own making. As Proust said, "The past is hidden . . . in some material object of which we have no inkling."


And though our memory remains inscrutable, the CPEB molecule... is the synaptic detail that persists outside time. Dr. Si's idea... is a molecular theory of explicit memory that feels true... Because it embraces our essential randomness, because prions are by definition unpredictable and unstable, because memory obeys nothing but itself. This is what Proust knew: the past is never past. As long as we are alive, our memories remain wonderfully volatile. In their mercurial mirror, we see ourselves.


I wonder if Lehrer has read Faulkner? What's interesting here is that, while reading this, we compulsively exercise our memory to test what we're reading. The process we are reading about is -- if true -- happening again and again as we remember and re-remember. A trip down memory lane is a chemical workout for our proteins and prions. We are changing the structure of our brains in the same way I'm changing the status of memory bits in my computer's RAM and on servers somewhere as I type these words. 

So, recalling what we learned about taste and smell in the Escoffier chapter, does exercising the mind in this way, make it better at doing this sort of thing? Just as eating more garlic probably makes me more sensitive to garlic (up to a point), does thinking and remembering make you better at thinking and remembering?

It will take a few days (coming up soon) but by mid-summer I will be a trash sorting machine, capable of processing a staggering volume of waste with barely a thought. Is the fact that I automatically approach every problem in an analytical way -- frequently coming up with a clever solution so quickly I get strange looks and have trouble explaining how the solution might work -- a result of my "doing" philosophy on a daily basis? There are clearly limits to what I can grasp (QCD!), but I can "sort" what I can grasp quite readily. This would explain insights I've only arrived at recently of books or subjects I've thought about for decades. (Like my "what victory looks like" military history insight. But both that and my "Napoleon" is really "Napoleon+Berthier" insights were derived from fresh data inputs. My wine-inspired generalization of the Eisenhower strategic view from WW2 was simply seeing that you could apply the same logic to a variety of situations.)

I've also come to appreciate Proust's unplanned approach to writing, as described above, since I find that my best material and insights flow from the writing process and not from "thinking." (This contradicts some of what I just said and also what Lehrer said about "contemplation." When I've re-read my previous blogs, my favorite passages have preceded quotes that support my comments, yet I almost never consciously planned that. I would have to say that what I like best came out when I wasn't thinking... or at least not planning. And this relates to what I recently said about "Mozart" moments being more satisfying than "Salieri" moments: We are pleasantly surprised by "Mozart" moments because they are like working with an inspired partner. Proust, in that passage I've still not been able to find, wrote about the desire to share special moments with another and how the act of sharing actually undermines the moment for us (almost always). But we can, on occasion, share those moments with our unconscious selves. Isn't one of the great appeals of the creation of art the trick of getting our conscious minds out of the way so that "we" can create at a deeper level? And isn't that why our dreams can be so inspired?


After writing the above, I went to the gym and it occurred to me that exercise probably works in a similar way -- the more you do the easier it is. It wouldn't surprise me if we grow more sensitive to endorphens the more we work out. And it wouldn't surprise me if our bodies get better at turning exercise into muscle the more we work out. As a process, bodybuilding is probably not unlike developing a taste for good food or the way we develop memory. And of all of these things, memory seems to be the most permanent. If you don't continue exercising you will lose muscle. If you avoid good food you will lose the taste for good food. But the only way to lose memories is to alter them or for the brain structures to come apart -- which is not normal.


Next - 138. Paul Cezanne

No comments:

Post a Comment