Our Neurogenetic Archives: A Few Notes

I have a guitar student, and she had a high school assignment to write on John Locke and was worried. I piped up, unwisely: "Ask me anything about John Locke! I'm here to help ya!" She had the vaguest notion of what Locke was up to, but she did know he influenced the risk-takers and revolutionaries who established Unistat. I told her Locke has been shown to be pretty far-wrong with his notion of our minds at birth as tabula rasa. Already, I had lost her.

But aye...I think the jury has come in with a unanimous decision on this: we come equipped, fully loaded. For presumably many but not all imaginable things. This has been established, in historical time, a few seconds ago. Or say 1950-now.

But to what extent are we loaded? Is it only activated with experience in-the-world, with language, with education? Certainly we inherit a shuffled deck of genes from mom and dad. Is that it?

(Aside: this genetic inheritance, modified by drugs, learning, changes in environment, bombardment by cosmic rays, alterations in diet, etc: this is my best unpacking of "Plato's Problem" as mentioned briefly in the review of Knight's book on Chomsky, below.)

In his lecture after winning the Nobel Prize for Medicine in 1968, Marshall Nirenberg talked about "genetic memories." Well of course, our genes can be said to have "memories" in a certain metaphorical sense, but details about this metaphorical sense? As I tried to read his lecture (quite technical...but it turns out Nirenberg was wrong about "nonsense codons"!), I can't get a line on it. He's certainly not going off about how the Akashic Records were "right after all!" or anything like that. Nirenberg gets as close to mentioning the astral plane as Keanu Reeves gets to winning Best Actor.

But that was way back in 1968.

Since then, there's been an explosion of knowledge about epigenetics: it turns out experience-in-the-world of our immediate forebears does have influence on our genes/lives. Poverty has been linked to epigenetic changes and mental illness, for example. Epigenetics is the study of how genes get expressed, and the more I read about it the more my head spins. RNA has much ado about gene expression. It's not merely a "messenger," as many of us were told in skool. Some genes get turned on or off like a binary light switch; others get modulated like a rheostat, gradually becoming more and brighter, or less and dimmer.

Here's another example from the past year: the methylation of the genes coding for the hormone oxytocin - a hormone linked to nurturing, trust and social skills - can get taxed by intense emotional experiences. What a wonderful example of the new reality of understanding biology: a gene that helps us do very important things such as falling in love with baby as soon as she is born? It's processed in the brain, like a drug. (Hell: I see oxytocin as one of the more interesting endogenous drugs we have, and we can synthesize it too!) This hormone/drug, via social interaction in the world, affects our behavior, and the social world/environmental feedback can alter the expression of the gene. This circular-causal feedback looping of nature/nurture ---> nature/nurture, ad infinitum, till death do us part - seems like a microcosm of how Everything works. (And remember: then the epigenetic effects can get inherited by the next generation, via what happened historically in the environment, and just, wow. So: death is not the end of our story. We're connected in ways we didn't know before.)

Gosh dad!: Father may pass down more than his genes: his life experience too?
Oh, my: a bad night's sleep can epigenetically alter your genes.
Our genetic cups runneth over: epigenetic drugs are in the works.
Not fair: Study of Holocaust survivors show trauma passed on to children's genes.

Think of how all this impacts the roiling and boiling issue of income inequality...

There's plenty more where that came in. A fine readable book for non-specialists that I can point to 'cuz I read it and was enthralled: Nessa Carey's The Epigenetics Revolution: How Modern Biology Is Rewriting Our Understanding of Genetics, Disease, and Inheritance

Combine this with a few books on the new synthetic biology, CRISPR techniques, and what the hell: quantum computing and ye head shall be spaghettified.

But back to the neurogenetic archives. They seem to have some ontological status outside the drawing room where the Theosophical expert waxes on about past lives. But to what degree?

Darold Treffert is a psychiatrist who's been studying savants and autistic people with extraordinary abilities in some domain of life. He's been at it for many decades. He became personal friends with Kim Peek, the person "Rain Man" was based on (though that character was a composite of many savants, says Treffert). In the beginning he was a traditional scientist who read Jung and thought it wasn't science: too soft. Now he thinks Jung was on to something; he thinks we may have genetic memories of things experienced in the past by others whom we often cannot identify. See his two books (mentioned in the text linked to) and give us a better explanation.

How wild this is! We can inherit knowledge? We can get bashed in the head and suddenly write symphonies, when before we couldn't even carry a tune? (Being somewhat conservative in certain areas, I'd rather not get my head bashed in and instead risk continuance of not being a genius.) Treffert says we inhabit a metaphorically left-brain (linear, rational) society; maybe activate latent abilities by spending more time doing what the Kulchur is telling us as "wasting time": doing art. (Here's yet another argument for Basic Income?)

Timothy Leary and Robert Anton Wilson have a collectively dizzyingly rich series of speculations on neurogenetic memory, based on their reading in genetics, mythology, neuroscience, history, anthropology, and literature; they scattered their ideas throughout their many books, and I'd point to Leary's Info-Pyschology and Wilson's Prometheus Rising for starters...

David Foster Wallace, in an essay on David Lynch collected in A Supposedly Fun Thing I'll Never Do Again, riffs on our topic, saying our internal impressions and moods are, "An olla podrida of neurogenetic predisposition and phylogenetic myth and psychoanalytic schema and pop culture iconography." (p.199 in my copy) I hadda look up "olla podrida."

Well, now I said to myself, "I think I write too much for this texting world. I'll try to make this OG spew a short one," and so I'll end with a quote from my favorite cognitive neurolinguist, George Lakoff:

"When we understand all that constitutes the cognitive unconscious, our understanding of the nature of consciousness is vastly enlarged. Consciousness goes way beyond mere awareness of something, beyond the mere experience of qualia, beyond the awareness that you are aware, and beyond the multiple takes on immediate experience provided by various centers of the brain. Consciousness certainly involves all of the above, plus the immeasurably vast constitutive framework provided by the cognitive unconscious, which must be operating for us to be aware of anything at all."
Philosophy In The Flesh: The Embodied Mind and Its Challenge to Western Thought, p.11

Thanks for bringing your immeasurably vast constitutive framework of your cognitive unconscious to the OG: see ya!

                                      художник Боббі Кемпбелл зробив цю графіку для мене

The Drug Report: Crisis In Psychopharmacology

It's been at least 30 years since a truly new drug has hit the market that addresses the needs of patients suffering from depression, anxiety, manic depression (now rather bloodlessly called "bipolar disorder"), and schizophrenia. Any "new" drugs in the last 30 years have been basically some variation on an older, established drug (called "Me Too" drugs), in an effort of competing drug companies to keep up with the competition. These non-new "new" drugs are almost always marketed as "blockbuster" or "revolutionary" therapeutics, touting less side effects than older, competing drugs. They are not new and the side effects are just different, not less. 50 or so psychiatric drugs bring in $25 billion a year in Unistat alone. And they're pretty lousy.

(I know, I know: you'd be far worse off without the one that worked for you. Hey: they do some good. For some people. I want better drugs for you, is all. And we were promised them with the 2000 mapping of the human genome. So...where are they? Later.)

                                                        serotonin

The drugs people use - by every estimate I've seen between 20% to 25% of the Unistat population takes  at least one of these - were discovered by accident. By serendipity. In the 15 years after 1945. In 1952 a tuberculosis drug didn't work for TB, but iproniozid sure elicited euphoria when tested! Bingo: the first antidepressant. The drug that became Tofranil was supposed to work for schizophrenics, but it didn't help them, only make them run naked into town, laughing. Another antidepressant. In 1949 lithium was discovered, by accident, to treat manic depression. In 1957 Leo Sternbach was about ready to give up his research into a class of antihistamines, things were looking like a dead-end, when he stumbled onto the benzodiazepines: your Valium, Xanax, Lorazepam, Klonopin, etc: an empire of anti-anxiety drugs, and a huge influence on the tonality of culture in the West in the latter half of the 20th century.

With better technics, we learned much more about neurons and neurotransmitters. The SSRIs seemed to treat depression and anxiety. They were really the last big breakthrough. Ever since then, clinical trials that have made it to Stage III have been nothing but huge, sad, very expensive wastes. And so Novartis, Glaxo-Smith-Kline, Astra Zeneca, Pfizer, Sanofri and Merck have by and large quit trying. They've halted clinical trials, moved onto research that shows more promise. The pipeline for new psychopharmacological drugs is dry.

                                    psilocybin, very much like serotonin in structure

Wait a minute: with more neuroscientists than ever before, far better imaging devices, a tremendous acceleration of knowledge about the human brain over the past 30 years...why? And mental health takes an increasing toll on us. If not you, someone you know. Why is this so difficult? Is it because what R.D. Laing called "the medical model" finally showed its hand? (A pair of nines?)

Again: our technology to map with ever finer-grains our cells, genes, and organs is greater than ever. We now have a deeper understanding of the human genome, an explosive discovery of the complexity of the epigenome, increasing understanding of how our environment and microbes interact with us...why don't we have a drug that will cure depression by now? Are we simply too complex to understand? Were we destined to be granted a brief window of time in which a few "happy accidents" would yield up as good as it gets, and it all ended 30 years ago? What about our computing power and pharmacological knowledge? Isn't it also subject to Moore's Law: a doubling roughly every 18 months? Shouldn't we have had a bevy of breakthroughs by now?

What are we doing wrong?

In 2011 Eli Lilly thought they had a breakthrough for schizophrenia. They'd given PCP to mice, then their new drug and...the mice calmed down! Everything went well. They got to Stage III clinical trials (humans) and 18 months later the drug was dead. Placebos worked just as well. Lilly is another company that has all but given up now too.

                                    LSD: like psilocybin and serotonin, structurally

Some New Ways of Thinking and Genuine Promise 
Steven Hyman of Harvard and M.I.T. knows this field well. He was quoted in an article I read as admitting of his colleagues, "People are tired of curing mice."

Let's go back to the last breakthough: Prozac and all its cousins.

It had been assumed that, when those happy accidents occurred, there must be a theoretical basis. Pharmacologists have always acted like they were on top of what was going on, but the trade secret was they were faking it: when a drug worked, it went on the market, people used it and they "worked" well enough, but at first the chemists and psychiatrists had no idea why. With better understanding of the brain, they found the ancient model of the imbalance of humors as an explanatory scheme. Only they juiced it up: they found  these drugs altered neurotransmitters. Therefore, the lack of the neurotransmitter caused the disease! It seemed quite plausible, and very much like the hardcore finding that insulin works for diabetics.

Nassim Nicholas Taleb says this is a classic case of the "reverse-engineering problem": drop an ice cube on the floor and then go play cards with your friends in the other room. Can you visualize the cube breaking down into a tiny pool of water? Of course you can. You walk back into the kitchen and see a tiny pool of water where you had dropped the cube. It's pretty straight-forward. Now: imagine walking down the street and coming upon a tiny pool of water. A little spot of wet. How many ways can you dream up the cause of this spot?

A cop comes upon a drunken man looking for his keys, at night, under a streetlight. The cop asks the drunk why he keeps looking under the streetlight, and the drunk says it's because the light is so much better there.

Obviously, even our best researchers have been looking where the light was bright. And the reverse-engineered explanation of our not-all-that-great/we-can-do-better psychopharmacological drugs? Human. All-too human.

The neurotransmitters are not the cause of the mental illness. They merely point at the underlying cause; neurotransmitters (dopamine, serotonin, norepinephrine, etc) are tangential and partial. Reverse-engineering to allow more serotonin to remain in the synaptic gap between neurons was a genius move; too bad there are a handful of studies that show SSRIs work little better than placebos. (For some people they have worked well enough; I don't want to slight this!) All in all, there's a "truthiness" about depression drugs.

We treat everyone the same in studies, while knowing they have variable epigenomes. This is receiving some major research and seems quite promising, to my eyes. We have a semantic problem with experts dealing with a patient, making observations and tests, then naming the disease they "have," which is a major problem: people and diseases do not fall into our socially-constructed and convenient categories as well as we'd like. This problem is now far more acknowledged than ever, which seems promising to me. One example is the Research Domain criteria: we map behavioral abnormalities and symptoms and link them to specific causes in the brain, without the label of "schizophrenia" or "panic disorder." Why is this approach better? Because it's more targeted. Instead of looking at one or two neurotransmitters that "cause" schizophrenia, we try to find out specifically what causes people to hear voices, or become catatonic.

The idea that we must take 18 years from conception through clinical trials is being re-thought. Even more crucially for mental disease: non-human animal studies long ago reached diminished returns. Now the idea is small-scale, carefully controlled studies on humans will speed up the process and may yield breakthroughs in shorter periods.

Another area of promise: when a drug failed, it often worked for a few people. But our gold standard of drug testing: double-blind and placebo-controlled? The rules were that if the placebo worked as well as the drug, throw out the drug. But the people who were helped probably should have told us something.

Along those lines, there is a strong call to restore abandoned or "invisible" clinical trials to correct the scientific record. We may learn some very interesting things from "failed" trials.

The techniques surrounding stem cells have accelerated at an incredibly dizzying pace upward and for the better: now researchers can test cells and drugs in a a dish and make very good guesses as to whether a compound would have some efficacy.

With the mapping of human genome in 2000, hundreds of utopian promises were made that now seem embarrassing or outright quackery. But there was reason to be optimistic. We thought because we were very complex, we'd have the most genes, but instead of 100,000 we only had about 21,000. Grapes have more genes than us: this was nothing like what we'd expected. Worse: 13 years later we now know that a "bigger" system - in terms of complexity - governs the genome: the epigenome. It turns out that RNA plays a far, far bigger part than we'd thought. The complexity can seem overwhelming.

In 2002 researcher Andrew Hopkins came up with an eye-opening paper, the "druggable genome": Okay: we'd thought we had 100,000 genes. We have closer to 21,000. He estimated that only about 10% of those genes coded for proteins that could bind to small molecules, which is how drugs work, basically. So: about 2,100 genes. But he estimated that, of those, only about 20% would be likely to involve diseases. So now we're down to about 420 possibilities for targets. And then he guessed we'd already discovered 50% of those (probably accidentally?). We only had 210 targets left? For all diseases, not just mental illnesses? Not exactly a rosy scenario. But...

Cheminformatics! This is a burgeoning discipline using the aforementioned computational doubling: there are tens of thousands of compounds in digitized libraries. Do you test them all? Two guys wrote  an algorithm to teach a computer to sift through a welter of data on TB, which is becoming antibiotic-resistant. A Big Deal, quite threatening to all of us, potentially. Their algorithm said: find all compounds that are like the drugs that used to work on tuberculosis. So you get that data set. Then the algorithm says, throw out every compound known to be toxic to mammalian cells. You have a smaller set, but a safer one to work with. The algorithm discovered a 40-year old drug that was shown to have anti-TB properties but had been forgotten.

Even more interesting and promising: researchers in Cambridge, MA have taken messenger RNA (mRNA), an ultra fragile molecule which, when injected activates the body's immune response, tweaked a couple of "letters" in its nucleotide sequence, and made a non-fragile mRNA that does not turn on the immune system. What this could do is take the information from the DNA in a gene and make it "fix" missing or broken proteins in another cell, in effect causing a patient with a (probably inherited?) protein abnormality to make a drug inside their own cells!

Nessa Carey, a gifted explainer of how epigenetics works in our bodies, has urged us to be cautious about getting too excited over drugs based on DNA-RNA, because so far, "One of the major problems with this kind of approach therapeutically may sound rather mundane. Nucleic acids, such as RNA-DNA, are just difficult to turn into good drugs. Most good existing drugs - ibuprofen, Viagra, antihistamines - have certain characteristics in common. You can swallow them, they get across your gut wall, they get distributed around your body, they don't get destroyed too quickly by your liver, they get taken in by cells, and they work their effects on the molecules in or on the cells. Those all sound like really simple things, but they're often the most difficult things to get right when developing a new drug."

Finally, there is a very real call to combine all our new technologies with an active looking for happy accidents, like in the 1945-60 period. We find as many compounds that could possibly have efficacy, get people willing to be guinea pigs to try them (we have far better ways to guess at what's likely to have horrendous side effects or death-dealing qualities, but we're by no means "covered" here), and see what happens! Yes, the dark side is that the poor will probably be the ones to sign up...How do we find new things to try? "Scientists Map All Possible Drug-Like Chemical Compounds." It turns out the drunk looking for his keys was far more accurate an analogy than we might've guessed. Or wanted to guess. Check out all the unexplored chemical "space" yet to be charted! It reminds me of the incredible number of phenethylamines and tryptamines that Alexander Shulgin mapped: but a drop in the ocean? (Shulgin deserved the Nobel Prize for Chemistry: just read-up on his career! It's almost criminal he didn't get the Prize.) It's like looking for signs of life in the Milky Way! Or more prosaically: like geologists learning how to more profitably drill for oil. It's also about algorithms and possibilities and adventure and hellacious mistakes yet to be made.

To all of us looking for better living through chemistry: Bon appetite! I do think we may make it through this bottleneck to a whole new world of more sophisticated drugs that will make all the ones we've had since 1945 look primitive. Maybe?

Some Of The Works Consulted:
The Epigenetics Revolution by Nessa Carey
"No New Meds," by Laura Sanders:
http://www.sciencenews.org/view/feature/id/348115/description/No_New_Meds
Happy Accidents: Serendipity In Modern Medical Breakthroughs, by Morton A. Meyers
"The Psychiatric Drug Crisis" by Gary Greenberg:
http://www.newyorker.com/online/blogs/elements/2013/09/psychiatry-prozac-ssri-mental-health-theory-discredited.html
PIHKAL: A Chemical Love Story, by Alexander and Ann Shulgin
"Where Are All The Miracle Drugs?" by Brian Palmer:
http://www.slate.com/articles/health_and_science/human_genome/2013/09/human_genome_drugs_where_are_the_miracle_cures_from_genomics_did_the_genome.single.html
"Messenger RNAs Could Create a New Class of Drugs," by Susan Young:
http://www.technologyreview.com/news/512926/messenger-rnas-could-create-a-new-class-of-drugs/
"Faster, Smarter and Cheaper Drug Discovery":
http://www.sciencedaily.com/releases/2013/03/130321131920.htm
Serendipity: Accidental Discoveries In Science, by Royston Roberts
Hope or Hype: The Obsession With Medical Advances and the High Cost of False Promises, by Richard A. Deyo and Donald L. Patrick
"Experts Propose Restoring Invisible and Abandoned Trials to 'Correct the Scientific Record'":
http://www.sciencecodex.com/experts_propose_restoring_invisible_and_abandoned_trials_to_correct_the_scientific_record-114055
The Black Swan: The Impact of the Highly Improbable, by Nassim Nicholas Taleb

Where The Hell Am I?

Often, when meditating whilst sitting quietly or even walking alone with "my" thoughts, I often use the gimmick of thinking about the Bohr Model of the atom (leave aside that it can be viewed as a "flawed" model for now), and how we're made up of atoms, which have a tiny nucleus with neutrons and protons "inside." And inside that are just all sorts of quarks and other surrealist "material" shenanigans.

And I read once in some popularization of quantum mechanics that the nucleus is so small relative to the electrons buzzing around in discrete "orbits" or "outer shells" that, if the nucleus were an orange put at the center of the 50 yard line at the Rose Bowl, then the electrons are whirling around - relatively speaking - outside the entrance gates, all around. What's "inside" all that "space"? It's empty! (But it's probably "really" not...no time to get into it now, here.)

Hell, every-thing else on this planet seems subject to the same laws of physics, and as Stephen Dedalus said, we are "ineluctably constructed upon the incertitude of the void." (Ulysses, p.697, "Ithaca")

[Interestingly to me, Joyce wrote Ulysses between 1915-1922; it was published in 1922. Quantum physics would show there was a physical basis for this poetic line, but not until 1925-27 or so.]

And therefore "I" am mostly empty space. "I" just seem solid because "I" can only make investigations with the sensoria Nature gave me: clunky stuff. Gigantic, really. And seemingly a plenum of bone, skin, blood, lymph, viscera. But - and "I" still think on one level this model "is" legitimate - "I" seem really quite ghost-like. "I" only bump into stuff because the stuff "I" bump into has roughly the same levels of non-emptiness that "I" have. What a world!

Usually this has served me well: thinking of myself, as Bucky Fuller said, "I seem to be a verb." Yea: what's not all about the empty space seems more about electrons and energy exchanges between "me" and my surrounding environment. I meditate on this physics and get outside of my (mostly empty?) "self."

I end up summoning some picture of myself as a cloud of energy, with a module near the top that seems to want to make everything into some solid "meaning." But that module seems utterly foolish and but one of the modules that make up what Marvin Minsky called The Society of Mind: what's going on seems a "booming buzzing confusion" of energies, everywhere and everywhen. When I do this I've entered what the phenomenological sociologists call a "finite province of meaning." This particular province of meaning seems about blissful meaninglessness, and it's a second cousin to being stoned on cannabis, only it's still legal. For now...

Going "Up" One Level
But lately - say, the last 24 months - I've been trying to understand the human genome. It turns out to be  absurdly complex, for the OG. But it's abecedarian compared to what I found out about epigenetics. HERE's an amusing short explanation about some of what is entailed by epigenetics. He does it far better justice than I could; I'm afraid I'd bore you with my explanations about methyl groups and histones and how your grandmother's smoking habit effects your health. My favorite metaphors so far for the genome and the epigenome are this: the genome is the hardware; the epigenome tells the genome what to do with its information, and when. Talk about complexity!

So getting back to trying to find out where "I" am: who and what I seem to be is not only atoms and the void, but information inherited roughly 50/50 from mom and dad, plus the environments I've accidentally been born into or found myself in, the choices I made about what environments to go into (and "environments" here means something closer to what McLuhan meant than saying "I grew up in the San Gabriel Valley area of Los Angeles County"). Although geography does seem to matter quite  a lot. But what my parents worried about, what they ate, what their parents experienced...and just an enormous amount of CHANCE occurrences seem to be a lot about where "I" am.

Then I found out something wonderfully disturbing that makes what I've mentioned so far seem trivial.

Going "Up" Another Level
In the 20th century, modern medicine finally arrived. O! The things we learned! About surgery (lots of insanely brutal war wounds provided ample practice), and what worked and what didn't, and doctors caught up to the washing their hands dealio. And we began to merge our physics (harnessing light) and chemistry with technology and imaging, and...we're on our way! We even found out we'd been acting like superstitious fools for millenia: if we wipe out bacteria, we'd live a lot longer, and healthier. And so: antibiotics (miracles!), antiseptics of all sort, cleaning products in every modern home. But we were wrong about bacteria: we need Them to maintain a healthy immune system. And oh wow: just sooooo much more.

You know this "I" that I'm trying to find? Turns out "he" is part of a system that's not only genome and epigenome, but microbiome. 90% of the cells in "me" are bacteria. And I'm healthy! "I" took a long bike ride today, got all kinds of work done, had some Big Laffs. But if "I" am 90% bacteria...I'm not sure what to think. And it turns out bacteria in my gut influences what I think and feel.

Who is running the show here?

Preliminary Ideas About Where the Hell "My" "I" "Is"
I understand the history of modern "self" hood had to do with rationalistic ideas about agency and law and responsibility. It was a convenient fiction. If some crime was committed, we want to gather the evidence and convict that rational actor for his wrongdoing and make that person "pay" a debt to another convenient fiction: The State. Or "society." But if we're driven by things our ancestors did and we're mostly empty space or bacteria, as the kids say, WTF?

At this point I take a deep breath and remember what Robert Anton Wilson said, in generalized account of what the Copenhagen Interpretation of quantum mechanics: every model we make to account for some aspect of "reality" tells us as much about our own minds as it does Nature, or what's "out there." As we grew up, toddling around some environment, as mostly empty space, our genes being played by histones and methylations and other Damned Things, we were constantly ingesting atoms and incorporating them into our "selves" without knowing it. Most of us still seem blase about the whole schmeer! And even then we were mostly bacteria. And if our parents found out this fact, they probably would've killed us. Literally. With antibiotics and a lot of scrubbing.

We're toddling around and our brains are receiving signals and ignoring others, setting up our nervous system to perceive the world a certain way and - this is crucial - not other possible ways. But some kid on the other side of the world was making grooves in his brain, connecting neural clusters in a different schema. That kid was "learning" a different language, for one thing. And language, being part of the world, also influences further how we'll "see" the world, and take action. (Sorry anti-Whorfians! You're on the outs, now.)

And yet: many of us grow into adulthood and enjoy enduring alliances and deep, satisfying relationships with someone from a remote (relative to "us") region of the world. We're terrifically malleable, plastic. But not infinitely so. Yep: I was born in LA, grew up there, lived in Colorado for a a few minutes, then moved back to LA, lived in a few areas in the vast sprawling metropolis around La-La Land, then moved to a different state within the state of California, a place called "Berkeley." And yet: I have friends who speak Chinese, who are also mostly empty space and bacteria. And it's good.

Okay, okay. I'm starting to feel better now. "I" accept my verbishness, my existence as a dissipative structure, and don't really care all that much where "I" am. Because, not being a solipsist, I assume you're reading this now, and you are enough like me, so what does it matter? How do I know I'm not being dreamed by some gaseous vertebrate of astronomical heft? I don't. Hell: maybe YOU are dreaming all this? And "I" don't care. This seems like a cosmic funhouse to me. All of it. What the hell: I'll just assume we sort of exist, and that it matters, bacteria and all.

Bloomsday/Father's Day: A Berkeleyite Navel-Gazes

1.) To loyal OG readers (4?) : sorry to have taken so long to get a blather out. OR: Bless me Father, for I have not been persistent, but a recent study shows we learn persistence from our Fathers, so whattya gotta say fer yourself, hmmmm? (I hesitate to commit the Genetic Fallacy and discount their findings simply because they's a buncha Mor-mons...Or are they?)

2.) As I read Ulysses, one of the themes that continues to ricochet-echo through my life are the ideas - mine and my culture's, or mine versus my culture's - of genetic inheritance. When we first meet Stephen alone, he's thinking about this, influenced by his reading in Theosophy and many, many other sourcebooks. Hermeticism and related ancient ideas - including Plato - placed the astral "soul" or epicenter of self-consciousness or the seat of eternal divine light...in the navel. Yep! Your belly-button. Yourself as something re-incarnated? Your omphalos is Ground Zero. Joyce publishes Ulysses in 1922, so he's pre-pre-pre modern genetics, knowledge about which has exploded since then. It will be a long time before we have a Grand Synthesis of how DNA-RNA epigenetic megacomplexity actually works. Gosh, it may take another seven years, at the rate we're going!

                                            Jim Gavin's portrait of James Joyce's father, 
                                                  John Stanislaus Joyce

3.) One of the corollaries of Stephen Dedalus's and Joyce's thinking is that: maybe I'm not as much of my father's son as my culture is pressing me to believe. The biological link was for Joyce undeniable; it's the - for lack of a better word - spiritual link that he wonders about. And he has his reasons. Look at Simon Dedalus in Ulysses. He's a minor character, Stephen's father, known around Dublin as a raconteur of wit, a fun guy to be around and a fine tenor, is modeled on Joyce's own father (who did not like Ulysses, but was proud of his son's success). John Stanislaus Joyce (James Joyce's biological father) was also a loudmouth about politics and religion, a mismanager of money, a drunk, and...now the less said the better.

4.) The hermetic idea of the bellybutton/navel as a linked source to all of the soul or consciousness's previous incarnations? What a wonderful idea, eh? As Stephen walks alone along the beach in the late morning of June 16, 1904, after teaching his class, we're in his stream of consciousness, and, at one point, we read:

The cords of all link back, strandentwining cable of all flesh. That is why mystic monks. Will you be as gods? Gaze in your omphalos. Hello. Kinch here. Put me on to Edenville. Aleph, alpha: Nought, nought, one.


I loved this bit the first time I read the book. Not only wonderful portmanteau words like "strandentwining" (oddly: seems like a precog-inkling of the double-helical structure of DNA, not discovered by Watson and Crick [the latter was probably influenced by LSD] until 1953), but the idea that the umbilical cord could be used like a telephone, to call back to Eden. Navel-gazing by the introspectives, meditating throughout all of all history: maybe they can get in touch with their origins? In the early years of the telephone, numbers were much shorter, and you called a switchboard operator to patch you through. Stephen imagines the number for Eden is 11-001, which reminds me of the digital code sequence I'm using right now to communicate with you. It also reminds me of the neurogenetic archival material that mystics and some imaginative scientists have thought we could access, if only we use the correct techniques or ingest the appropriate molecules...

                              I liked Milo O'Shea as Leopold Bloom in Joseph Strick's
                              daring 1967 film. But when I read Ulysses I don't picture
                              O'Shea in my mind when Bloom's perambulating. YMMV

5.) As you know, the other main male character in Ulysses is Leopold Bloom. Ever since his son Rudy died 11 days after birth, he and his wife Molly have not had sex. When we read the entire book, we find that thoughts of Rudy impinge on Bloom's mind at odd intervals, and the scene at the end of the "Circe" episode (where Bloom rescues a drunken Stephen in the red light district, late at night), where Bloom sees an apparition of Rudy as a boy reading Hebrew...is one of the most profoundly moving passages in all of literature for me. I get choked up just writing about it here.

In the famous internal monologue of Molly, at the end of the book, we see she has not emotionally reconciled with Rudy's death either.

Ulysses is one of the two or three most closely-scrutinized-by-scholars works of fiction in history, and it's difficult to write about it without boring the hell out of people who have turned considerable personal energies towards it exegesis. But for those who've always wanted to "get to the book but haven't yet found the time," I'll just state that Bloom is, in some ways, the spiritual father of Stephen. Bloom takes Stephen home with him, and they share a cup of eucharist...errr...hot cocoa. Bloom listens to the young intellectual Stephen and realizes he's an odd egg...like himself. He even fantasizes that Stephen can move in with he and Molly. Molly can give him singing lessons while Stephen can teach Molly italian. Why, Stephen might even end up marrying his teenage daughter Milly, and become his son-in-law! But it will not happen. Bloom is an outsider in Dublin, and Stephen realizes he can't find himself as an artist unless he gets out of his hometown.

6.) One of my favorite passages illustrating how these two seemingly very different characters are like Father and Son comes in the section, late at night, back at Bloom's house, and it's a section that suddenly appears in the style of a 19th century scientific textbook, but more likely is a parody of the Catholic catechism:

Did Bloom discover common factors of similarity between their respective like and unlike reactions to experience?


Both were sensitive to artistic impressions musical in preference to plastic or pictorial. Both preferred a continental to an insular manner of life, a cisatlantic to a transatlantic place of residence. Both indurated by early domestic training and an inherited tendency of heterodox resistance professed their disbelief in many orthodox religions, national, social and ethical doctrines. Both admitted the alternately stimulating and obtunding influence of heterosexual magnetism.


This catechismal flow also discusses their differences, but the thrust of the thing? They're like father and son, although not related by blood at all.

And with this I'll cut it short. I know you really wanted to see what 7.) had to say, but I will leave this off here: the book ends at the address 7 Eccles Street.

Let us, on this Bloomsday and tomorrow's Father's Day, reflect not only on our biological fathers, but on our spiritual ones as well?

Moral and Political Thought

Picking up where I left off the last: This business of hardwired political views as a new science is, as they say in Hollywood, "blowing up;" it's becoming a big deal. The metaphor "hardwired" ought to be looked at for a second: does our moral and political behavior really work as if someone had spot-welded all the parts together, with no going back and unplugging these wires from over here, plugging those in there, soldering a new cable into a jack bought at the parts store because a component was discovered that would access other systems was spied in the manual, etc? No changes can occur? It's a "done deal" at some point?

Well, apparently lots of scientists would like us to think so. There's the Grail of isolating the one gene, or a cluster of genes, that would sure enough predict that your two-year-old would indeed grow up to read Noam Chomsky...or Ann Coulter. In Sasha Issenberg's piece I linked to above, a political strategist reads some new Psychology books and decides he'll help his candidate by focusing ads based on "thinkers" versus "feelers." Haidt says most of our political "thinking" is "moral instinct papered over," and what a good writer Haidt is! It's lines like that that get people persuaded you're really onto something. And maybe he is. A quick diversion:

In a previous blogspew on Jonathan Haidt, I linked to his YourMorals.org test. Here's another test, called Political Compass. It's much shorter than the battery Haidt's colleagues want you to take, and one of its main purposes is to get you out of thinking on the dumb Euclidean line of
Left<-----------Centrist------->Right; it's more 3-D-ish, and it's HERE if you wanna take it. I think it gives a certain snapshot of who you are politically, and by association, morally. I've taken the test three times now, most recently within 72 hours of my writing this. HERE's my result. I'm a "left libertarian." A quite pronounced one, it seems.

Robert Anton Wilson explains the Dumb Game of Left-Right Euclidean politics in a way no one else I've ever seen come close. [Thanks to the guys at rawilsonfans.org.]

Haidt says he wrote The Righteous Mind not to try to convince anyone to switch their allegiances, but to try and understand the Other better, and possibly minimize the hate. (His name rhymes with "fight," not "fate," as I've been listening to people talk about him lately.) I liked the last two paragraphs of Jonathan Ree's pithy review in The New Humanist. The most I can implement from this book, I take it, is to use George Lakoff's framing techniques to talk about Authority, Sanctity, and Loyalty in a way that might catch the ear of a "conservative." I'll get back to Haidt in a moment, but I was talking about genes and morality...

I think we can safely agree that we have a reflex for self-flattery, that emotions do rule, that our reasoning is like a lawyer's trying to win a case. And of course our political ideas are NOT totally deliberative. I do think environment and experience and learning all contribute, especially if one has tested one's own presumptions many times. I've done it. I've read National Review. I read Francis Fukuyama's The End of History. I once had a job where I was offered a transfer to another library branch, one in a very beautiful and wealthy section of Los Angeles, where most of the patrons I'd meet would be old, very wealthy Republicans. I had very long hair and thought I'd try testing myself here - I'm pretty sure I was a left-libertarian then too - and I was prepared to experience lots of nastiness. But after a few years, I really liked most of the patrons, and they were very sweet to me. Some were obviously very conservative, but they asked me questions about politics and I gave them my honest takes, and they respected me.

I'd say about 8-12% of the patrons I ran into there were the classic mean, pinched, bitter, evil, ugly rich old white people. Most were surprisingly, delightfully pleasant. This opened my eyes. It didn't change my politics much though.

                                  William Irwin Thompson. "The history of the soul is always
                                  the history of the voiceless, the oppressed, the repressed."
                                  Photo by Michael Laporte

But do I think genes will explain all this? No, despite NYU psychologist Ned Jost's findings in the "The End of the End of Ideology" paper, mentioned in Issenberg's excellent overview article. Indeed, read the section on Jost's work and see if it doesn't look isomorphic to the Rattray-Taylor oral/anal lists I gave in my previous blogpost. Jost: We're not divided by class, geography or education so much as by temperament. 


Temperament. O! How I urge you, Dear Reader, if you haven't already, to read the first lecture in William James's Eight Lectures on Pragmatism. If Haidt and his data-set don't come off as "tender-minded," then you weren't paying attention.

It seems the search for a genetic substrate that will explain macro-world phenomena gets you funding. It allows scientists to do what they really want to do: wake up in the morning and go to work to solve some problem of some sort. If their hypotheses don't work out the way they had envisioned, they write that up anyway: it's still good science: if we thought it worked this way, we were probably wrong. Meanwhile, jobs and knowledge were created. And though searching genomes and testing genes has gotten much cheaper over just the past year or so, it's still heady stuff. It's creative work, too. Get the ideas. Figure out how to test them. Figure out how to test your test. It's brainy stuff, aye.

But I remember the great generalist and one-time M.I.T. lecturer William Irwin Thompson - who dropped out of academia - saying about hardcore sociobiology something along the lines that it's sheer bullshit to say you're going to find a gene to be an auto-mechanic. You say morality and a political bend is more "basic" than something as particular as Thompson's reductio ad absurdum? You're probably right, but do we realize how dizzyingly complex "genes" are? If you try to keep up with this stuff, it seems like it's getting to be like particle physics. Or worse. It may be even more complex than that, especially if we take into account epigenetics, where RNA plays a much bigger part than we'd imagined. It's not just DNA sending RNA "the" message to other genes to make proteins z, q and x3. That was the older, simpler days. Now the environment has genes and RNA-DNA feeding back in ways we didn't guess, hopping genes, "junk DNA" that is turning out to not be so junky...I mean check out this recent article, "Chromosomes Organize Into 'Yarns': May Explain Why DNA Mutations Can Effect Genes Located Thousands of Base-Pairs Away," from a few days ago.

Although why I'm some left-libertarian socialist and those who love Fox News are decidedly...<cough> not, and I find their morality, extrapolated/writ large as basically stupid, devolutionary, and sadistic, I don't really know why I'm like this. One parent was staunchly Democrat. Another a Republican who never really got into the Issues. I have a sibling who went from extreme Right Wing Christian born-again Evangelical to a sort of New Church, Jesus said to heal the sick and feed the poor leftist Christian. Most of the other immediate family members aren't very political, although if they are, it's right wing authoritarian stuff.

Ultimately, it's genes, something like ethological "imprinting," family upbringing, peer group at puberty, geography, historical moment, accidents like meeting a very influential person at one point or another when you're vulnerable to some sort of change, and...more accidents and happenstance. Genes? Yes. And probably a bunch of stuff we have only the slightest inklings about. Here's one we've just begun to really gain deeper understandings about:

There's a neuroeconomist named Paul Zak. He wondered about how economies are effected by the human action of "trust," which seemed kind of nebulous to me. He thought - and it made sense to me - that the more trust, the better the economy works. Here's a short article on the "trust hormone" that we make endogenously and secrete when we make eye contact, hug, smile at each other, fall in love, etc. The video of Zak is about 3 minutes long. So add to all the factors above: hormones.

                                        Neuroeconomist and "Dr. Love," Paul Zak

Finally, back to Jonathan Haidt. In my understanding of the world to date, there are some people who, like Oscar Wilde, thought/think that obedience to authority was the Original Sin. In modern terms, these people have often transcended the socio-sexual Hive Morality and experienced neurosomatic bliss, then showed others how to do it. We got the Sexual Revolution from these people, largely. And I see that movement as still going strong, still playing out on the stage, at least in the West. When Authoritarian Men try to roll back gains women had made, even subject them to sexual humiliation, I think it's largely because women have made so many gains. Women are doing well, relative to men, at least in Unistat. By 2019 they will probably make up at least 60% of all graduate students. And they will continue to do well. As well they should. They aren't hurting men by doing well. But a small, loudmouthed, fairly fascistic set of men are responding to the changes - probably mostly unconscious of the deeper reasons why: their fear of losing Control - so they are making themselves very busy right now, shooting every toe on each foot, one by one...

                                                         Oscar Wilde: Heretic

Those who transcend Hive Morality - cranks, neophiles, inventors, deviates, heretics - drive human evolution. The drag on cultural evolution - the Authoritarians, the inflexible Loyalists, the Sanctimonious about some Angry God they've projected from within themselves onto the rest of us: they are most of the Church, most of the Politicians and Legislators ("Well...let's look at precedent!"), and Mammon-worshippers. They're nationalists, often racists and small-minded loudmouths who say they're for individual liberty but do quite something else. These are the drags on progress. Haidt thinks they deserve to be understood by "liberals" because these people - the guardians of Hive Morality - don't want things to change, because it represents a threat to their status in the primate hierarchy.

Given my political bend, no wonder Haidt's equal Big Six doesn't wash with me.

Epigenetics: the Revenge of Lamarck!

[If you're a non-biologist and you know Lamarck's name it seems likely that you think of his idea that giraffes have elongated necks because they needed to stretch them to get to the food above, and the ones that stretched the most sent their stretched necks on to their offspring, and eventually the giraffes with the longest necks got the most food, most progeny, longer necks, etc...]

Probably the most popular metaphor for the human genome - or any living thing's genome - is the "blueprint." The blueprint was devised by some architect and is a map that will determine how a structure will be built, presumably down to the last detail. It's neat, sleek, elegant, intellectual and, depending on how you unpack it personally, possibly depressingly deterministic.

Another metaphor I noted, after the race between Craig Venter and company and the government-backed NIH to sequence the human genome pretty much ended in a dead heat around June of 2000, it was written more than a few times that, yes, we have sequenced three billion base pairs, but now we have a brand new Steinway...but we don't know how to play piano yet! Much work was to be done to find out how/why/when genes are expressed, how they might combine, how some are "turned off" and others "turned on," and, if we learn this - how to play "the piano" (possibly the Hammerklavier Sonata?) - we might find out how to cure cancer, prevent genetically inherited diseases, and possibly prolong human life and delay senescence.

All along a slew of researchers were busy studying individual genes and trying to figure out why, even in monozygotic (formerly known as "identical") twins, the two people could be so vastly different by age 20. 

Jean-Baptiste Lamarck, whose theory of acquired characteristics had been relegated to the dustbin of science, was all the while looming over this research: could something other than the digital inheritance of mom's and dad's genes - and possibly a random mutation or two, as allowed by neo-Darwinism - explain all the odd disparities? It turns out that the study of the organic molecules that coat genes on the DNA double helix regulate their expression. And of course RNA is involved in a very big way, probably bigger than you were taught in high school. RNA is not simply the messenger-boy anymore, oh no. The mechanisms of epigenetics seem byzantine in complexity, but a wonderful new book makes it understandable to a dummkopf  like myself.

(Here's Lamarck, whose ideas were left for dead, but who rose in the late 20th/early 21st century to haunt us with complexity and wonder):

I just finished a fascinating book called Epigenetics: The Ultimate Mystery of Inheritance, by Richard C. Francis, a Ph.D in neurobiology and behavior from Stony Brook who did post-doc work at Stanford and Berkeley. It arrived earlier this year and is, as far as I can tell, the first book on epigenetics written for the intelligent layperson. 

What's odd is that, for some reason, I didn't see Lamarck's name once in the book. I wonder why? Maybe I'll write Francis and ask. He's a freelance science writer now, and a good one.

Many others who have reviewed Francis's book have made the Lamarck connection, though...The story of the triumph of neo-Darwinism and the decline of Lamarckism is filled with political intrigue (see Paul Kammerer's downfall, and polymathic Arthur Koestler's The Case of the Midwife Toad, for the inklings of a true mystery, and I know full well the delicious irony of linking here to a creationist's writing!), which I will not go into now. But it seems safe to say that both Darwin and Lamarck were "right" and their theories are so advanced now that they wouldn't recognize the intricacies of depth they have engendered.

The most beautiful thing about Francis's book, to me, was the very real "light at the end of the tunnel" promise of epigenetics as the way to find a cure for cancer. 

The most disturbing thing about the book is that your life may have been altered forever by mom's stress levels while you were in the womb. This new approach to genetics eerily explains how a famine in the 1940s still affects the physiology of people born recently. It places a tremendous burden on our responsibilities to optimize our environments, and not simply from toxins: from stress-inducing environments too, which cause our DNA's expression to alter even when we are middle-aged. 


In addition, we can inherit from our grandfathers, not just our fathers. Epigenetics has a rather fat role to play in explaining the obesity epidemic. The implications of this study - in which DNA no longer plays the role of Executive - are astonishing. Here's Francis:

"Epigenetics is the study of how these long-lasting, gene-regulating attachments are emplaced and removed. Sometimes epigenetic attachments and detachments occur more or less at random, like mutations. Often though, epigenetic changes occur in response to our environment, the food we eat, the pollutants to which we are exposed, even our social interactions. Epigenetic processes occur at the interface of our environment and our genes." - from the Preface

The complexity found in epigenetic research and its implications staggers me, and this book arrives just as I felt like I was finally getting a decent handle on the 23 chromosomes and what they do, which was already abstruse for me. The old idea of "OGOD," or "one gene, one disease," has gone the way of phlogiston or the luminiferous ether long ago, to say the least...(With some well-known exceptions, but it seems that something like the clear-cut genetic understanding behind, say, Huntington's Chorea is fairly rare. The epigenetic basis for most diseases are fuzzy.)

It seems crystalline at this point that, a detailed working-out of the dynamics of epigenetics will go a long way towards the human species learning to "play that piano" well. (How about the Goldberg Variations? That should cure cancer, at the very least! One would hope...)

I think we underestimate the value of writers who so thoroughly understand dizzyingly complex scientific ideas that they can produce a book about them for the intelligent lay public and make the ideas seem far less opaque. Richard C. Francis has accomplished this, and kudos to him! May many people read this book! There's even some good stuff for baseball fans, even if it involves steroids, Mark McGwire, Jose Canseco, and epigenetics. (But why no mention of Lamarck?)