Biology

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So we profess ourselves to be the slaves of chance, and flies of every wind that blogs

Hello and good morning.  It’s Thursday again, against almost everyone’s better judgment.  Indeed, it’s the first Thursday (and the second day) of March, which is a new month (though the name is, of course, not new).

It being Thursday, it’s time once again for my traditional weekly blog post, which differs from my now-daily blog post only in that it follows the old pattern of a Shakespearean title and usually a picture…and, of course, this little introduction in which I note all these points, which is frankly rather tedious.  I should probably just quit doing it.

The trains were having severe troubles yesterday morning and yesterday evening.  In the morning, there was temporary suspension of the trains northbound from my usual station, due to what the fellow at the station referred to as a “train versus vehicle* event”.  The RTA was supposedly providing a “bus bridge” from that station to the next one north of the accident, and indeed, at long last, two full buses arrived bringing passengers from the station north of the event so they could continue south.  However, only one of the buses was heading back north, oddly enough, and that bus got full literally just as I was about to get on it.  I was the very one at whom the driver held out his hand, palm forward, and said, “No more passengers.”

So, grumbling, I stepped back, and I and the other remnants waited, asking when the next bus would be.  The fellow at the station did not know, though he guessed about ten minutes (ha ha).  After a while, he received notice that normal service was resuming.  This probably means no one had died in the “train versus vehicle event”, which I suppose is a good thing**.  I ended up being about an hour late to the office, and this was on Wednesday, which means there was payroll to do.  Also, we’re setting up and putting into practice a new program that I am heavily involved in, and we had two new people starting on a trial basis, who needed to be processed…and of course, meanwhile, we had at least three people out sick.  I was pretty stressed out, even relative to a normal day.

Then, last night, as I waited at the train station, the southbound train was announced to be late, and then announced to be later, and then that train was cancelled, and then the next one was announced to be late, and then later…

Eventually, it got to the point that, even if that next train got there at its announced later time, by the time I took it, then the two buses***, then walked from the stop to the house, it would be quite late.  And, honestly, I didn’t have anything (and certainly not anyone) waiting for me at the house, so it didn’t seem worth it to bother going.  I walked back to the office, and I slept here overnight.  And here I am writing this.

Such is my life—if you can call it that.  I hate it.  There’s nothing in it that’s of any real worth.  I’m still in chronic pain, I still have insomnia.  Obviously, I still have my dysthymia/depression, and of course, if I do have any neurodevelopmental difficulties that have hitherto gone undiagnosed, they certainly haven’t gone away.  I remain at least slightly uncertain in that latter category, because though I think the evidence is good, I do not quite trust my own judgment.

Can you blame me?

So, anyway, again, here I am, though metaphorically I am nowhere.  I also have a headache, which is probably at least partly tension related.  And I’m tired.  I’m not sleepy, but I am tired, almost all of the time.  I honestly don’t know what to do.  I mean, I know what I think I ought to do.  But it’s hard to get an “is” from an “ought”—though all “oughts” come from “ises****” contrary to what humeans seem to think—and I don’t have quite the will yet to overcome the activation energy wall created by biological drives/resistances to get to the other side.

I’m working on a way around.  There are things one can do to reduce one’s resistance in the short term, to lower that activation energy barrier.  But I’m not really interested in drugs, nor am I willing to deal with people who deal in illicit ones, and alcohol just tends to make me sleepy (and yet not to stay asleep or feel rested).  I do step swiftly into crosswalks when the lights change, hoping someone will not pay attention to traffic signals and will just hit me; they would deserve to have to deal with it, since pedestrians in the crosswalk have the right of way when obeying signals.  But so far—though many seem tempted—even when I tell them to hit me, none of them have.  I don’t know whether to feel irked about that or to be slightly pleased that so many people are more careful than one might expect.

Oh, well.  It doesn’t matter.  I suspect I’ll find a way to get back where I came from one way or another before too long, blisters and biological drives notwithstanding.  There must be some kind of quantum tunneling that can eventually get me through that mental barrier*****.

There’s no reason to expect things to head in the opposite direction, though, so I don’t really have any sense of optimism or even of possibility.  But in the meantime, I’ll keep writing these daily posts on days when I work, which will include Saturday this week.  You can continue to look forward to them, if you do, but for a limited time only.

TTFN

tri rail

Golden Glades Tri Rail Station – no trains present

*Is a train not a type of vehicle, though?

**Although, honestly, given the trouble the driver of said vehicle had caused—presuming that it was that driver’s fault, which is not certain but seems more likely than not—I can’t help but wish that they at least could have been injured badly, and if you had asked me at the time, I would almost certainly have said they ought to have been killed (but not their passengers, of course, unless the accident was caused by such a passenger).  After all, given the number of people whom they inconvenienced, and the economic, social, and psychological losses they thereby engendered, and the physical stress they created among many people (me included) it seems likely that their escapade led to diminished health and even premature death in one or more than one person.  But they probably didn’t do it on purpose, so perhaps the death penalty would be excessive.  Still, I don’t hear about such accidents happening in countries where commuter trains are much more common than here in the US, whereas something of the sort happens almost monthly just during the times of my commutes.

***I probably wouldn’t have walked.  I’m trying to rest the healing blister on my right foot, at least from more than a mile of walking at a time.  It seems to be doing well.

****That’s a plural that doesn’t want to be spelled.

*****I think this was Dylan’s original first line of All Along the Watchtower, but it just didn’t scan.  It turned out fine when fixed, though, and Jimi’s version was even better, as Dylan himself is said to have admitted.

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Some blistering insights into soles like hobbits’ (and holes like ants’)

It’s Monday again.  Yippee ki yawn.  Aren’t you all just so excited?

I don’t have much interesting to report or discuss today, because I haven’t really done anything interesting to report or discuss, nor thought anything interesting to report or discuss since my last blog post.

I have continued trying to sort out different shoes and related footwear.  I walked home from the train station on Friday, but it turned out that the new blister on my right foot had not resolved itself very well during the two weeks since it had happened, which is quite annoying.  The blister on the left foot was fine; I had very carefully, and under effectively sterile conditions, poked a pin-hole in it the day after my very long trek, to drain the fluid, and it basically has now become just a thickened area of foot sole, and it gave me no trouble over the course of my five mile walk on Friday evening.

On the right foot, for reasons I don’t recall clearly, I had elected not to drain the blister—I think it just didn’t seem to have as much fluid in it—and a little more than halfway through my trek on Friday, it started to give me more trouble, as if I had something sharp stuck in my shoe.  I didn’t have any such thing; I checked.

Anyway, I rested on Saturday, during which my right foot was sore still, and I decided to drain that blister as I had the other.  I then walked about six miles (total) yesterday, and though the blister is still irritating, it’s better than it was.

Here’s my off-the-cuff hypothesis for why the course of the left and right blisters was different:

By draining the fluid from the left blister, I allowed the two layers of affected skin to re-adhere to each other, and through that process to become firmer and tougher—at least tougher than they were when the fluid of the blister was present.  On the right foot, however, even as it was recovering, there was still fluid in the blister—it never got completely reabsorbed, and the skin layers thus never re-adhered.  So, once I walked a long enough distance, those two layers of skin were effectively separate and lubricated, and began to rub back and forth against one another.  Just as pertinently, at the edges of the former blister, shearing forces pulled the aforementioned layers of skin further apart, causing new damage.  So, it was actually therapeutic to drain the fluid—as long as I protected rigorously against the risk of infection—than to allow the other to retain its fluid in this case.

As I thought about this, I wondered why such a thing might be the case.  Why would our evolutionary heritage saddle us with a process, on the base of our feet of all things, that would be counterproductive to healing?  Then it hit me*.  Our ancestors throughout almost all of evolutionary time did not wear shoes or boots or any such thing, and they certainly didn’t walk for long distances on paved roads.  They would have formed calluses on the soles of their feet, starting at an early age—presumably as soon as they were able to walk—and repetitive shearing forces, such as are produced by the rubbing of the sole of a shoe, would not apply.  They would have had the soles of hobbits, if you will, and those are pure, tough soles indeed.

So, in some senses, our footwear is detrimental.  Of course, in other ways, it’s extremely useful, and does protect us from sharp and hard objects on the ground against which even thicker skin wouldn’t have defended adequately.  Broken glass is certainly something one wouldn’t want to encounter with bare feet.

Then again, I recall that once, quite a while back, a Kenyan athlete won the Olympic marathon in bare feet, so there aren’t severe disadvantages.  It’s got to be pretty hard to do on pavement, though, and the next time that athlete ran, and won—if memory serves—he did wear shoes.

And you wouldn’t want to go walking through a snowy landscape without something on your feet, at least for warmth.

Still, it makes one wonder how many of the things we wear on our feet are relatively unnecessary and even counter-productive.  If I had gone barefoot a lot over the years, would I not even require footwear much anymore, living as I do in south Florida, where there is almost never anything close to snowy weather?  It’s certainly likely that the risk of fungus would be lower!  It’s interesting to wonder whether even the problems I have with my right ankle, due to an old severe sprain, would be fewer if I had not worn various types of footwear.

It’s also interesting to think about how much of the footwear industry is just a self-sustaining fiction, like so many other industries.  Just to be clear, though, I would not claim that this is any kind of conspiracy or evil plot by malevolent capitalists at Nike and Adidas and Reebok and New Balance.  That’s just a stupid thought, and if you seriously entertain it, you should probably slap yourself.

I’m sure there are worse and better people (by whatever criteria one might specify) at nearly all levels in such companies, as there are in the ranks of social services, as there are working in governments, as there are in charitable organizations, as there are in hospitals.  No, the footwear industry, at all its various levels, is just a big, spontaneously self-organizing system, like everything else about civilization.  There is no master plan, and there is no master**, any more than there is a planner, architect, CEO or Personnel office in an ant hill or a termite mound or a bee hive or a school of fish or a flock of birds.  Things happen, and the things that tend to be self-sustaining tend to sustain themselves***, while the things that don’t tend to do so simply fade away with relatively little fuss.

This is part of, or at least related to, why I hate people calling elected officials our “leaders”.  They’re not leaders, nor should they be, and they certainly don’t “run” the country or state or city or whatever.  They’re employees, managers, servants.  And believe me, they are just as fundamentally clueless as everybody else about what’s happening in the world and what to do about it.  They just sometimes pretend otherwise, even to themselves.  But just because they fool themselves, doesn’t mean you have to let them fool you.

That’s about it for today.  It’s been a weird progression of thoughts, but that seems appropriate, given the eventual topic of discussion.

caveman walk

*It’s just like what happened when I was standing in a park and wondering why a frisbee appears to get larger and larger as it gets closer and closer.

**Except the Time Lord called The Master.

***Duh.

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I blog not you, you elements, with unkindness

Hello and good morning.  It’s Thursday, February 2nd, and the day of the week on which I’ve long done my semi-traditional blog posting.

I don’t know whether I have the energy to hunt for a Shakespeare quote to alter and/or a picture to put at the bottom, both vaguely related to whatever “subject” I address in the blog.  But, of course, by now, you readers will know what decision I, the writer, will have made, even as you read the words I’m writing while I do not know.

It’s a bit wibbly-wobbly, timey-wimey, isn’t it?

Of course, the biological experience of time is much more malleable and irregular than the actual nature of time, but time is not a simple, straight, linear dimension.  It’s warped by the planet beneath your feet, among many other things.  Your physical body’s tendency to want to follow the most “direct” path through it‒and the fact that the planet is in the way, preventing you from following that path‒creates what we call gravity, locally.

When you’re free-falling, you’re coasting through time (and space, of course), and it’s the ground that actually accelerates you once you reach it.  It’s a hell of an acceleration if you’ve been pursuing your geodesic unimpeded for long by the time the ground throws itself into your path.  Human’s aren’t built to withstand that kind of acceleration.

I’m writing with my smartphone again, today, by the way.  It’s just too annoying to deal with the laptop at the bus stop.  I also wrote more words than I really had meant to write yesterday, probably because I type faster on the laptop, but I don’t think the increased number of words was associated with an increase in actual content.  I think the signal-to-noise ratio, if you will, of my blog post yesterday was lower than it has tended to be with the phone.  That’s not an objective measure, however, and others may disagree.

As for my thumbs, they already feel a bit better than they did, and they’re not giving me too much trouble now.  I have some Voltaren cream (or is it an ointment?) that I can apply to the joints if necessary, though I already take round-the-clock NSAIDs every day for my chronic pain, so it’s not really recommended that I add the Voltaren, a strong NSAID in it’s own right.  It increases the risk for kidney damage and liver damage and stomach issues and so on.  But I’m already at risk for those things (though I take Omeprazole for my stomach protection) and I don’t see easy short-term solutions to the problem.

This is one of the conundrums (conundra?  Probably not) that make opiates and opioids both necessary and yet culturally difficult‒our non-psychoactive pain medications are literally toxic to our bodies above a quite low threshold relative to their analgesic powers.  Yet pain does not easily just go away on its own in many cases‒biology is subject to much stronger pressures for pain to persist than to allow it easily to be relieved, and those incentives will remain so in any evolutionarily stable form of life.

Opiates and the like can work against nearly any degree of pain with limited direct toxicity, but with diminishing success and tolerance, requiring increasing doses over time*.  But they do affect neural circuitry, reward, and motivation, among other things, and so their use is complicated‒and it’s additionally complicated by the fact that the treatment of pain, physical and psychological, is somewhat taboo in our society.

The use of various substances in one’s own body is even criminalized, and so black markets arise to take advantage of the inevitable demand.  And without matters being out in the open and subject to expert scrutiny and monitoring and education, various abuses and issues relating to lack of access to appropriate guidance and treatment and support arise and worsen.

And they will persist.

Do you think continuing to criminalize the use of drugs of various kinds will decrease abuse and death and even violence related to the drugs?  You hypocrites!  I say to you that it is the criminalization of that use that created the black markets and abuse and danger and sordidness‒and, indeed, the majority of the deaths‒in the first place!

You punish people for trying, however imperfectly, to treat chronic pain and those who suffer from it from addressing it, and are surprised that sufferers turn to the market you have created for illicit meds.  You have the temerity to be “shocked” that people die from the unmonitored, unregulated, inexpert use and manufacture of these things which you have removed from the bailiwick of expert awareness and oversight and monitoring.  You took an area that should have been medical and made it criminal and are stupid enough to be surprised that opportunistic criminals (whether they be gangs or governments or otherwise) are not as careful and caring as actual medical professionals.

And sometimes you are so hopelessly moronic as to imagine that further punishments of both producers and suppliers‒and even users‒of drugs will change the problem or decrease it or make it go away.  As if making an already suffering person’s life even more difficult and miserable is going to diminish their urge for relief and escape from at least some forms of pain, and their willingness to risk the permanent end to their pain that is death by overdose.  I’d need to exist macroscopically in all the ten spatial dimensions of M Theory to be able to give that the eye roll that nonsense deserves.

Phew.  That was a heckuva tangent.

I don’t actually use opioids or related medications, though I have been prescribed them in the past.  They interact with my rather peculiar nervous system in ways I find truly unpleasant, though they can help with pain.  So, instead, I suffer constant daily assaults on my kidneys and GI tract and my liver, and I accept that.

It’s not as though I will seek treatment if my organs fail.  I have no insurance, for one thing, but also, I just don’t see any point in trying to preserve my existence.  Heck, I’ve been told I have a possible recurrence or deterioration of my congenital heart problem‒I’m not fully convinced that it’s really any kind of recurrence‒for which I had heart surgery when I was 18, but I have no interest in pursuing possible further exploration or treatment of it, anyway.

Let my kidneys fail, let my liver fail, let my heart fail!  Blow, wind, and crack your cheeks!  Why would I try to preserve or prolong my existence when I don’t even like myself, let alone have anyone else nearby who likes me and spends time with me***?

Anyway, that went off the rails pretty quickly, didn’t it?  It also got longer than I expected.  Sorry.

I still don’t know the answer to my initial wondering about titles and pictures‒but you all do.  And I love you for it.

TTFN

windstormandmanscaled

*Though at least they don’t directly poison livers and kidneys, and the needed doses don’t keep going up without limit, though they are nevertheless often higher than most doctors are willing to prescribe.  This is largely because doctors fear having what happened to me happen to them, and who can blame them?  The only exception to this general hesitancy is with cancer.  People with cancer are allowed to be treated with whatever level of pain medicine it takes to reduce their pain, because in the typical human “mind” having cancer pain is different, and people with cancer are special.  They’re allowed to be dependent on pain medications, because surely they have the only type of pain that can go on and on without resolving and can steal all the joy from their lives, eventually killing them.  Anyone else is just a disgusting drug addict, a scum of the Earth, and deserves merely contempt**.

**The latter portion of the above paragraph is sarcastic.

***I cannot blame them, so don’t be defensive on my behalf.  I find myself infuriating and disgusting.

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Happy Boxing Day, everyone!

For those of you in the United States, just in case you don’t already know, Boxing Day is basically just the day after Christmas.  It’s celebrated in the UK, and apparently in Canada and other parts of the “Commonwealth”, though how exactly it’s celebrated is not clear to me.  It’s also not clear to me—after a few random, admittedly not very careful searches—just what the day actually celebrates, other than the day after Christmas, or to what the Boxing part of Boxing Day refers.

It doesn’t appear to have anything at all to do with the sport of boxing, nor the dog breed, boxers.  I don’t think it has anything to do with the Boxer rebellion in China, either—why would it?  It’s a bit of a mystery.  Maybe it’s related to people putting the gifts they didn’t really want that they received for Christmas back in their boxes to take to the store for refunds, or to put in the attic (or “loft” as they say in the UK).  I doubt that, though.

It’s been a slightly interesting weekend.  On Friday I bit the bullet and went to the evening dinner/party with the office, but I arranged things so that I didn’t need anyone to drive me there or to drive me all the way back to the house.  Instead, I took the train up to Delray Beach as soon as the office closed and walked to a hotel—The Hyatt Place at Delray Beach—where I’d decided to indulge in a rather large expense and reserve a room for the night.

From there, after a rest, I walked two blocks to the restaurant and immediately started ordering drinks to allow me to socialize, then had a pleasant evening with the people I know from the office.  It had begun to get cold—for south Florida, certainly—by that time, and I was pleased to have only a two block walk back to my nicely warm hotel room, where I cuddled up and slept off my drinks, had a continental breakfast in the morning, and then walked back to the train station at about eleven-ish (it was 3 miles…still is, as far as I know) and took the train back to Hollywood and thence to the house.

Since then, I’ve slept a great deal, which is really nice for me.  I tried to keep low on carbs for what I’ve eaten this weekend, because it turns out that I’ve probably become pre-diabetic.

I had been trying to see if I could do a near-vegan* diet, including plenty of legumes and other sources of protein, to see if it could help me be healthier and lose weight.  It rapidly did the opposite (I was gaining weight and I felt worse), and as I walked through a Walgreen’s one evening, thinking about my family history, I checked into the diabetic supplies area, amazed to note that one could buy a glucometer for less than twenty dollars!  I remember when you used to need a prescription to get one because you needed your insurance to pay for it, because they were expensive.

Anyway, not that day, but soon after, I bought one, and tested my fasting blood sugar a few days in a row, and found it to be slightly high, in the pre-diabetic range.  This is not terribly surprising, given my family history, but it was a well-needed confirmation of my suspicion.  I have to admit, on those few occasions when I’ve tried a carbohydrate-restricted diet, I have felt generally healthier.  But it’s been hard for me to maintain, for the temptations of carbs are everywhere, and are all the more difficult to resist when one is stressed out, as appears to be my default state.

But now I have blood glucose confirmation that things are going to go badly if I continue to indulge—and death by type 2 diabetes is too slow a process to make it appealing.  I also know that low carb diets have been objectively beneficial for me in the past—my resting pulse, which normally runs too fast (at over 100 bpm) went down to the mid-sixties, my total cholesterol to about 138, my triglycerides almost ridiculously low, and my HDL at a nicely normal range.  You get the idea.  I felt better, and I looked better (at least at the chemical, microscopic level), and it was only because I had trouble being motivated to control my appetite that I didn’t stick with that mode of eating.

So that’s the plan, or part of it, for the moment.  I’ll keep you posted on an intermittent basis on how things are going.

In the meantime, I’m on my way to the office, though there are far fewer people on the train today than usual—in fact, until five minutes before time for the first train to arrive, I was the only person waiting at the station.  I’m still waking up early, but then again, given how much I slept this weekend, at least I don’t feel worn out.  It’s good not to feel worn out already, first thing on a Monday morning, but I often already do feel that way.  So in that sense, it’s been a good holiday weekend.  Indeed, we did not work on Saturday, but I did have a nice (low carb) breakfast and a good walk to the train.

I hope you all have a nice several days in this last week of 2022.  Remember, since January 1st will fall on a Sunday, there will be a Friday the 13th in January—not one of the movies, but the day.  I always like those days.  They’re almost never bad luck for me (and there’s no reason other than self-fulfilling prophecies for them to be bad luck for anyone else).

Please enjoy your elaborate, traditional Boxing Day celebrations.  But if you do celebrate by boxing, please restrict yourselves to body blows.  Even with gloves and padding, just the inertial transfer of any blows to the head always does some damage to the brain, which tends to be both permanent and cumulative.  Many of us can’t afford to lose more than we already have lost.

*I like to make the joke that it’s ironic that people who only eat vegetables or similar here on earth use the term “vegan”, because the dominant native intelligent life forms in the Vega star system—the Vegans, in other words—are obligate carnivores.  Of course, that’s just a joke; there aren’t really any native species in the Vega star system—it’s too young a star to have evolved complex life.  The inhabitants there are all colonists.  But the dominant ones of those are obligate carnivores**.

**Earth people need not fear some kind of carnivorous alien invasion, though.  Any species that are products of completely separate evolutionary histories cannot readily eat any of the life forms from the other biosphere.  At best they would simply get no nutritional value from their meal—like pandas, as carnivores, trying to get enough food out of bamboo, but thousands of times worse, with only some minerals and electrolytes and perhaps a few simple biochemicals being useful.  But much more likely, the eaten life form’s own endemic microbes would begin to break down their hosts while in the new species’ ineffectual digestive system, and would cause physical and probably chemical damage to the eater.  Many very basic microbes are remarkably good at dining on things that complex life cannot digest…including said complex life.

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Some thoughts (on an article) about Alzheimer’s

I woke up very early today‒way too early, really.  At least I was able to go to bed relatively early last night, having taken half a Benadryl to make sure I fell asleep.  But I’m writing this on my phone because I had to leave the office late yesterday, thanks to the hijinks of the usual individual who delays things on numerous occasions after everyone else has gone for the day.  I was too tired and frustrated to deal with carrying my laptop around with me when I left the office, so I didn’t.

I’m not going to get into too much depth on the subject, but I found an interesting article or two yesterday regarding Alzheimer’s disease.  As you may know, one of the big risk factors for Alzheimer’s is the gene for ApoE4, a particular subtype of the apolipoprotein gene (the healthier version is ApoE3).  People with one copy of the ApoE4 gene have a single-digit multiple of the baseline, overall risk rate for the disease, and people with 2 copies have a many-fold (around 80) times increased risk.

It’s important to note that these are multiples of a “baseline risk” that is relatively small.  This is a point often neglected when discussing the relative risks of a disease affected by particular risk factors when such information is conveyed to the general public.  If the baseline risk for a disease were one in a billion (or less), then a four-times risk and an eighty-times risk might be roughly equivalent in the degree of concern they should raise.  Eighty out of a billion is still less than a one in ten million chance for a disease; some other process would be much more likely to cause one’s deterioration and demise rather than the entity in question.

However, if the baseline risk were 1%‒a small but still real concern‒then a fourfold multiplier would increase the risk to one in 25.  This is still fairly improbable, but certainly worth noting.  An eighty-fold increase in risk would make the disease far more likely than not, and might well make it the single most important concern of the individual’s life.

Alzheimer’s risk in the general population lies between these two extremes, of course, and that baseline varies in different populations of people.  Some of that variation itself may well be due to the varying frequency of the ApoE4 gene and related risk factors in the largely untested population, so it’s tricky to define these baselines, and it can even be misleading, giving rise to false security in some cases and inordinate fear in others.  This is one example of how complex such diseases are from an epidemiological point of view, and highlight just how much we have yet to learn about Alzheimer’s specifically and the development and function of the nervous system in general.

Still, the article in question (I don’t have the link, I’m sorry to say) concerned one of the functions of the ApoE gene (or rather, its products) in general, which involve cholesterol transport in and around nerve cells.  Cholesterol is a key component of cell membranes in animals, and this is particularly pertinent in this case because the myelin in nerves is formed from the sort of “wrapped up” membranes of a type of neural support cell*.

cns myelin

This particular study found that the cells of those with ApoE4 produced less or poorer myelin around nerve cells in the brain, presumably because of that faulty cholesterol transport, and that the myelin also deteriorated over time.

Now, the function of myelin is to allow the rapid progression of nerve impulses along relatively long axons, with impulses sort of jumping from one space (a “Node of Ranvier”) between myelin sheath and another rather than having to travel all the way down the nerve, which a much slower process, seen mostly in autonomic nerves in the periphery.  When normally myelinated nerves lose their myelin, transmission of impulses is not merely slowed down, but becomes erratic and often effectively non-existent.

myelin in general

The researchers found that a particular pharmaceutical can correct for at least some of the faulty cholesterol transport and can thereby support better myelin survival.  Though this does not necessarily point toward a cure or even a serious disease-altering treatment over the long term, it’s certainly interesting and encouraging.

But of course, we know Alzheimer’s to be a complex disease, and it may ultimately entail many processes.  For instance, it’s unclear (to me at least) how this finding relates to the deposition of amyloid plaques, which are also related to ApoE, and are extracellular findings in Alzheimer’s.  Are these plaques the degradation products of imperfect myelin, making them more a sign than a cause of dysfunction, or are they part of the process in and of themselves?

Also, it doesn’t address the question of neurofibrillary tangles, which are defects found within the nerve cells, and appear to be formed from aggregates of microtubule-associated proteins (called tau protein) that are atypically folded and in consequence tend to aggregate and not to function and to interfere with other cellular processes, making them somewhat similar to prions**.  It’s not entirely clear (again, at least to me) which is primary, the plaques or the tangles, or if they are both a consequence of other underlying pathology, but they both seem to contribute to the dysfunction that is Alzheimer’s disease.

So, although potential for a treatment that improves cholesterol transport and supports the ongoing health of the myelin in the central nervous systems of those at risk for Alzheimer’s is certainly promising, it does not yet presage a possible cure (or a perfect prevention) for the disease.  More research needs to be done, at all levels.

Of course, that research is being undertaken, in many places around the world.  But there is little doubt that, if more resources were to be put into the study and research of such diseases, understanding and progress would proceed much more quickly.

The AIDS epidemic that started in the 1980s was a demonstration of the fact that, when society is strongly motivated to put resources into a problem, thus bringing many minds and much money to the work, progress can occur at an astonishing rate.  The Apollo moon landings were another example of such rapid progress.  Such cases of relative success can lead one to wonder just how much farther, how much faster, and how much better our understanding of the universe‒that which is outside us and that which is within us‒could advance if we were able to evoke the motivation that people have to put their resources into, for instance, the World Cup or fast food or celebrity gossip.

I suppose it’s a lot to expect from a large aggregate of upright, largely fur-less apes only one step away from hunting and gathering around sub-Saharan Africa that they collectively allocate resources into things that would, in short order, make life better and more satisfying for the vast majority of them.  All creatures‒and indeed, all entities, down to the level of subatomic particles and up to the level of galaxies‒act in response to local forces.  It’s hard to get humans to see beyond the momentary impulses that drive them, and this shouldn’t be surprising.  But it is disheartening.  That, however, is a subject for other blog posts.

I’ll try to have more to say about Alzheimer’s as I encounter more information.  Just as an example, in closing, another article I found on the same day dealt with the inflammatory cells and mediators in the central nervous system, and how they can initially protect against and later worsen the problem.  We should not be too surprised, I suppose, that a disease that leads to the insidious degeneration of the most complex system in the known universe‒the human brain‒should be complicated and multifactorial in its causation and in its expression.  This should not discourage us too much, though.  The most complicated puzzles are, all else being equal, the most satisfying ones to solve.

*The cell type that creates myelin in the peripheral nervous system (called Schwann cells) is different than the type that makes it in the central nervous system (oligodendrocytes), and this may be part of why Alzheimer’s affects the central nervous system mainly, whereas diseases like ALS (aka Lou Gehrig’s Disease), for instance, primarily affect the nervous system outside the brain.

**The overall shape of a protein in the body is a product of the ordering of its amino acids and how their side chains interact with the cellular environment‒how acidic or basic, how aqueous or fatty, how many of what ions, etc.‒and with other parts of the protein itself.  Some proteins can fold in more than one possible way, and indeed this variability is crucial to the function of proteins as catalysts for highly specific chemical reactions in a cell.  However, some proteins can fold into more than one, relatively stable form, one of which is nonfunctional.  In some cases, these non-functional proteins interact with other proteins of their type (or others) to encourage other copies of the protein to likewise fold into the non-functional shape, and can form polymers of the protein, which can aggregate within the cell and resist breakdown, sometimes forming large conglomerations.  These are the types of proteins that cause prion diseases such as “mad cow disease”, and they appear also to be the source of neurofibrillary tangles in people with Alzheimer’s disease.

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The sweetest honey is loathsome in its own deliciousness. And in the taste destroys the appetite. Therefore, blog moderately.

Hello and good morning.  It’s Thursday again, so I return to my traditional weekly blog post, after having taken off last Thursday for Thanksgiving.  I’m still mildly under the weather, but I’m steadily improving.  It’s nothing like a major flu or Covid or anything along those lines, just a typical upper respiratory infection, of which there are oodles.  Most are comparatively benign, especially the ones that have been around for a while, because being not-too-severe is an evolutionarily stable strategy for an infectious agent.

An infection that makes its host too ill will keep that host from moving about and make itself less likely to be spread, to say nothing of an infection that tends to kill its host quickly.  Smart parasites (so to speak) keep their hosts alive and sharing for a looong time.  Of course, “smart” here doesn’t say anything about the parasite itself; viruses are only smart in the sense that they achieve their survival and reproduction well, but they didn’t figure out how to be that way—nature just selected for the ones that survived and reproduced most successfully.  It’s almost tautological, but then again, the very universe itself could be tautological from a certain point of view.

It’s an interesting point, to me anyway, to note that today, December 1st, is precisely one week after Thanksgiving.  Of course, New Year’s Day (January 1st, in case you didn’t know) is always exactly 1 week after Christmas.  It’s unusual for Thanksgiving to precede the first of December by a week, because the specific date of Thanksgiving varies from year to year (and, of course, if Thanksgiving were to fall on the 25th of November, December 1st would not be exactly one week later).  It’s an amusing coincidence; there’s no real significance to it, obviously, but I notice such things.

Anyway.

My sister asked me to write something about the vicissitudes of sugar (not her words), and though I don’t mean to finish the topic here today, I guess I’ll get started.  Apologies to those who are waiting for me to finish the neurology post, but that requires a bit more prep and care, and I’m not ready for it quite yet.  Life keeps getting in the way, as life does, which is one of the reasons I think life is overrated.

It’s hard to know where to start with sugar.  Of course, the term itself refers to a somewhat broad class of molecules, all of which contain comparatively short chains of carbon atoms, to which are bonded hydrogen and hydroxyl* moieties.

Most sugars are not so much actual free chains as they are wrapped up in rings.  The main form of sugar used by the human body is glucose, which is a six-membered ring with the rough chemical formula C6H1206.

glucose2

This is the sugar that every cell in the body is keyed to use as one of its easy-access energy sources, the one insulin tells the cells to take up when everything is working properly.  Interestingly enough, of course, though glucose is the “ready-to-use” energy source, it only provides about 4 kilocalories** per gram to the body, as compared to 9 kilocalories per gram for fats.

But the sugar we get in our diets is not, generally speaking, simple glucose.  It tends to be in the form of disaccharides, or sugars made of two combined individual sugars.  Sucrose, or table sugar, is a dimer of glucose and fructose, joined by an oxygen atom.

sucrose

Okay, I’m going to have to pick this up tomorrow.  I’ve gotten distracted and diverted by a conversation a few seats ahead of me.

There are two guys talking to each other at the end of this train car, and they are each seated next to a window on the opposite side of the train, so they’re basically yelling across the aisle to each other.  Their conversation is perfectly civil, and though they’re revealing a certain amount of ignorance about some matters, they are mainly displaying a clear interest in and exposure to interesting topics, from history to geography and so on.

At one point, one of the men started speaking of the pyramids and how remarkable their construction was, and I feared the invocation of ancient aliens…but then he followed up to say that, obviously, there were really smart people in ancient Egypt, just like we have smart people today who design and build airplanes and rockets and the like.  Kudos to him!

These men are not morons by any means.  They clearly respect the intellectual achievements of the past and present, and that’s actually quite heartening, because I think it’s obvious that neither one is extensively college-educated, if at all.

But why do they have their conversation from opposite sides of the train, so that everyone nearby has to hear it?  It’s thrown me off my course.

I’ll close just by saying that yesterday I finished rereading The Chasm and the Collision, and I want to note that I really think it’s a good book, and to encourage anyone who might be interested to read it.  The paperback is going for I think less than five dollars on Amazon, and the Kindle edition is cheaper still.  If you like the Harry Potter books, or the Chronicles of Narnia, or maybe the Percy Jackson books, I think you would probably like CatC.

CatC cover paperback

I’d love to think that there might be parents out there who would read the book to their kids.  Not kids who are too young—there are a few scary places in the story, and some fairly big and potentially scary ideas (but what good fairy tale doesn’t meet that description?).  It’s a fantasy adventure starring three middle-school students, though I’ll say again that, technically, it’s science fiction, but that doesn’t really matter for the experience of the story.

Most of my other stuff is not suitable for young children in any way—certainly not those below teenage years—and Unanimity and some of my short stories are appallingly dark (though I think still enjoyable).  If you’re old enough and brave enough, I certainly can recommend them; I don’t think I’m wrong to be reasonably proud of them.  But The Chasm and the Collision can be enjoyed by pretty much the whole family.  You certainly don’t have to be a kid to like it, or so I believe.

With that, I’ll let you go for now.  I’ll try to pick up more thoroughly and sensibly on the sugar thing tomorrow, with apologies for effectively just teasing it today.  I’m still not at my sharpest from my cold, and the world is distracting.  But I will do my best—which is all I can do, since anything I do is the only thing I could do in any circumstance, certainly once it’s done, and thus is the best I could do.

Please, all of you do your best, individually and collectively, to take care of yourselves and those you love and those who love you, and have a good month of December.

TTFN

*Hydroxyl groups are just (-OH) groups, meaning an oxygen atom and a hydrogen atom bonded together, like a  water molecule that lost one of its hydrogens.  This points back toward the fact that plants make sugar molecules from the raw building blocks of carbon dioxide (a source for the carbon atoms and some of the oxygen) and water (hydrogen and oxygen) using sunlight as their source of power and releasing oxygen as a waste product.  This was among the first environmental pollutants on the Earth—free oxygen—and it had catastrophic and transformative effects on not just the biosphere of the Earth but even on the geology.  The fact that the iron in our mines, for instance, is mainly in the form of rust is largely because of this plant-born presence of free oxygen in the atmosphere.

**A kilocalories is defined as the amount of energy needed to heat a kilogram of water by one degree centigrade.  We often shorten this term just to “calorie”, but that is actually only the amount of heat needed to raise a gram of water one degree centigrade (or 9/5 degrees Fahrenheit).  It’s worth being at least aware of the fact that what we tend to call calories are actually kilocalories.

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You’ve got some nerve!

It’s Saturday, the 19th of November in 2022, and I’m going in to the office today, so I’m writing a blog post as well.  I’m using my laptop to do it, and that’s nice—it lets me write a bit faster and with less pain at the base of my right thumb, which has some degenerative joint disease, mainly from years of writing a lot using pen and paper.

The other day I started responding to StephenB’s question about the next big medical cure I might expect, and he offered the three examples of cancer, Alzheimer’s and Parkinson’s Disease.  I addressed cancer—more or less—in that first blog post, which ended up being very long.  So, today I’d like to at least start addressing the latter two diseases.

I’ll group them together because they are both diseases of the central nervous system, but they are certainly quite different in character and nature.  This discussion can also be used to address some of what I think is a dearth of public understanding of the nature of the nervous system and just how difficult it can be to treat, let along cure, the diseases from which it can suffer.

A quick disclaimer at the beginning:  I haven’t been closely reading the literature on either disease for quite some time, though I do notice related stories in reliable science-reporting sites, and I’ll try to do a quick review of any subjects about which I have important uncertainties.  But if I’m out of date on anything specific, feel free to correct me, and try to be patient.

First a quick rundown of the two disorders.

Alzheimer’s is a degenerative disease of the structure and function of mainly the higher central nervous system.  It primarily affects the nerves themselves, in contrast to neurologic diseases that interfere with supporting cells in the brain*.  It is still, I believe, the number one cause of dementia** among older adults, certainly in America.  It’s still unclear what the precise cause of Alzheimer’s is, but it is associated with the development of “cellular atypia made of what are called “neurofibrillary tangles” within the cell bodies of neurons, and these seem to interfere with normal cellular function.  To the best of my knowledge, we do not know for certain whether the plaques are what directly and primarily cause most of the disease’s signs and symptoms, or if they are just one part of the disease.  Alzheimer’s  is associated with gradual and steadily worsening loss of memory and cognitive ability, potentially leading to loss of one’s ability to function and care for oneself, loss of personal identity, and even inability to recognize one’s closest loved ones.  It is degenerative and progressive, and there is no known cure and there are few effective treatments that are not primarily supportive.

Parkinson’s Disease (the “formal” disease as opposed to “Parkinsonism”, which can have many causes, perhaps most notably the long-term treatment of psychiatric disorders with certain anti-psychotic medicines), is a disorder in which there is loss/destruction of cells in the substantia nigra***, a region in the “basal ganglia” in the lower part of the brain, near the takeoff point of the brainstem and spinal cord.  It is dense with the bodies of dopaminergic neurons, which there seem to modulate and refine motor control of the body.  The loss of these nerve cells over time is associated with gradual but progressive movement disorders, including the classic “pill-rolling” tremor, shuffling gait, blank, mask-like facial expression, and incoordination with tendency to lose one’s balance.  There are more subtle and diffuse problems associated with it, including dementia and depression, and like Alzheimer’s it is generally progressive and degenerative, and there is no known “cure”, though there are treatments.

Let me take a bit of a side-track now and address something that has been a pet peeve of mine, and which contributes to a general misunderstanding of how the nervous system and neurotransmitters work, and how complex the nature and treatment of diseases of the central nervous system can be.  This may end up causing this blog post to require at least two parts, but I think it’s worth the diversion.

I mentioned above that the cells of the substantia nigra are mainly dopaminergic cells.  This means that they are nerve cells that transmit their “messages” to other cells mainly (or entirely) using the neurotransmitter dopamine.  The term “dopaminergic” is a combination word, its root obviously enough being “dopamine” and its latter half, “ergic” relating to the Greek word “ergon” which means to do work.  So “dopaminergic” means those cells do their work using dopamine, and—for instance—“serotonergic” refers to cells that do their work using serotonin.  That’s simple enough.

But the general public seems to have been badly educated about what neurotransmitters are and do; what nerve impulses are and do; and what the nature of disorders, like for instance depression, that involve so-called “chemical imbalances” really entails.

I personally hate the term chemical imbalance.  It seems to imply that the brain is some kind of vat of solution, perhaps undergoing some large and complex chemical reaction that acquires some mythical state of equilibrium when it’s working properly, but when, say, some particular reactant or catalyst is present in too great or too small a quantity, doesn’t function correctly.  This is a thoroughly misleading notion.  The brain is an incredibly complex “machine” with hundreds of billions of cells interacting in extremely complicated and sophisticated ways, not a chemical reaction with too many or too few moles on one side or another.

People have generally heard of dopamine, serotonin, epinephrine, norepinephrine, and the like, and I think many people think of them as related to specific brain functions—for instance, serotonin is seen as a sort of “feel good” neurotransmitter, dopamine as a “reward” neurotransmitter, epinephrine and norepinephrine as “fight or flight” neurotransmitters, and so on.

I want to try to make it very clear:  there’s nothing inherently “feel good” about serotonin, there’s nothing inherently “rewarding” about dopamine, and—even though epinephrine is a hormone as well as a neurotransmitter, and so can have more global effects—there’s nothing inherently “fight or flight” about the “catecholamines” epinephrine and norepinephrine.

All neurotransmitters—and hormones, for that matter—are just complex molecules that have particular shapes and configurations and chemical side chains that make them better or worse fits for receptors on or in certain cells of the body.  The receptors are basically proteins, often combined with special types of “sugars” and “fats”.  They have sites in their structures into which certain neurotransmitters will tend to bind—thus triggering the receptor to carry out some function—and to which other neurotransmitters don’t bind, though, as you may be able to guess from looking at their somewhat similar structures, there can be some overlap.

dopamine

Dopamine

serotonin

Serotonin

epinephrine

Epinephrine

Neurotransmitters are effectively rather like keys, and their functions—what they do in the nervous system—are not in any way inherent in the neurotransmitter itself, but in the types of processes that get activated when they bind to receptors.

There is nothing inherently “rewarding” about dopamine, any more than there is anything inherently “front door-ish” to the key you use to unlock the front door of your house, or “car-ish” to the keys that one uses to open and turn on cars.  It’s not the key or the lock that has inherent nature, it’s whatever function is initiated when that key is put into that lock, and that function depends entirely on the nature of the target.  The same key used to open your door or start your car could, in principle, be used to turn on the Christmas lights in Rockefeller Center or to launch a nuclear missile.

Dopamine is associated with areas of the nervous system that function to reward—or more precisely, to motivate—certain behaviors, but it is not special to that function.  As we see in Parkinson’s Disease, it is also used in regions of the nervous system involved in modulating motor control of the body.  The substantia nigra doesn’t originate the impulses for muscles to move, but it acts as a sort of damper or fine tuner on those motor impulses.

Neurotransmitters work within the nervous system by being released into very narrow and tightly closed spaces between two nerve cells (a synapse), in amounts regulated by the rate of impulses arriving at the bulb of the axon.  Contrary to popular descriptions, these impulses are not literally “electrical signals” but are pulses of depolarization and repolarization of the nerve cell membrane, involving “voltage-triggered gates****” and the control of the concentration of potassium and sodium ions inside and outside the cell.

synapse

A highly stylized synapse

The receptors then either increase or decrease the activity of the receiving neuron (or other cell) depending on what their local function is.  It’s possible, in principle, for any given neurotransmitter to have any given action, depending on what functions the receptors trigger in the receiving cell and what those receiving cells then do.  However, there is a fairly well-conserved and demarcated association between particular neurotransmitters and general classes of functions of the nervous system, due largely to accidents of evolutionary history, so it’s understandable that people come to think of particular neurotransmitters as having that nature in and of themselves…but it is not accurate.

Okay, well, I’ve really gone off on my tangents and haven’t gotten much into the pathology, the pathophysiology, or the potential (and already existing) treatments either for Parkinson’s or Alzheimer’s.  I apologize if it was tedious, but I think it’s best to understand things in a non-misleading way if one is to grasp why it can be so difficult to treat and/or cure disorders of the nervous system.  It’s a different kind of problem from the difficulties treating cancer, but it is at least as complex.

This should come as no surprise, given that human nervous systems (well…some of them, anyway) are the most complicated things we know of in the universe.  There are roughly as many nerve cells in a typical human brain as there are stars in the Milky Way galaxy, and each one connects with a thousand to ten thousand others (when everything is functioning optimally, anyway).  So, the number of nerve connections in a human brain can be on the order of a hundred trillion to a quadrillion—and these are not simple switching elements, like the AND, OR, NOT, NAND, and NOR gates for bits in a digital computer, but are in many ways continuously and complexly variable even at the single synapse level.

When you have a hundred trillion to a quadrillion more or less analog switching elements, connecting cells each of which is an extraordinarily complex machine, it shouldn’t be surprising that many things can go wrong, and that figuring out what exactly is going wrong and how to fix it can be extremely difficult.

It may be (and I strongly suspect it is the case) that no functioning brain of any nature can ever be complex enough to understand itself completely, since the complexity required for such understanding increases the amount and difficulty of what needs to be understood*****.  But that’s okay; it’s useful enough to understand the principles as well as we can, and many minds can work together to understand the workings of one single mind completely—though of course the conglomeration of many minds likewise will become something so complex as likely to be beyond full understanding by that conglomeration.  That just means there will always be more to learn and more to know, and more reasons to try to get smarter and smarter.  That’s a positive thing for those who like to learn and to understand.

Anyway, I’m going to have to continue this discussion in my next blog post, since this one is already over 2100 words long.  Sorry for first the delay and then the length of this post, but I hope it will be worth your while.  Have a good weekend.

*For instance, Multiple Sclerosis attacks white matter in the brain, which is mainly long tracts of myelinated axons—myelin being the cellular wraparound material that greatly speeds up transmission of impulses in nerve cells with longish axons.  The destruction of myelin effectively arrests nerve transmission through those previously myelinated tracts.

**“Dementia” is not just some vague term for being “crazy” as one might think from popular use of the word.  It is a technical term referring to the loss (de-) of one’s previously existing mental capacity (-mentia), particularly one’s cognitive faculties, including memory and reasoning.

***Literally, black substance.

****These are proteins similar to the receptors for neurotransmitters in a way, but triggered by local voltage gradients in the cell membrane to open or close, allowing sodium and/or potassium ions to flow into and out of the cell, thereby generating more voltage gradients that trigger more gates to open, in a wave that flows down the length of the axon, initially triggered usually at the body of the nerve cell.  They are not really in any way analogous to an electric current in a wire.

*****You can call that Elessar’s Conjecture if you want (or Elessar’s Theorem if you want to get ahead of yourself), I won’t complain.

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Some discussion of cancer–not the zodiac sign

Yesterday, reader StephenB suggested that I write about what I thought might be the next big medical cure coming our way—he suggested cancer, Alzheimer’s, and Parkinson’s diseases as possible contenders—and what I thought the “shape” of such a cure might be.  I thought this was an interesting point of departure for a discussion blog, and I appreciate the response to my request for topics.

[I’ll give a quick “disclaimer” at the beginning:  I’ve had another poor night.  Either from the stress of Monday night or something I ate yesterday (or both, or something else entirely) I was up a lot of last night with reflux, nausea, and vomiting.  So I hope I’m reasonably coherent as I write, and I apologize if my skills suffer.]

One hears often of the notion of a “cure for cancer”, for understandable reasons; cancer is a terrifying and horrible thing, and most people would like to see it gone.  However, my prediction is that there will never be “a” cure for cancer, except perhaps if we develop nanotechnology of sufficient complexity and reliability that we are able to program nanomachines unerringly to tell the difference between malignant and non-malignant cells, then destroy the malignant ones and remove their remains neatly from the body without causing local complications.  That’s a tall order, but it’s really the only “one” way to target and cure, in principle, all cancers.

Though “cancer” is one word, and there are commonalities in the diseases that word represents, most people know that there are many types of cancers—e.g., skin, colon, lung, breast, brain, liver, pancreatic, and so on—and at least some people know that, even within the broader categories there are numerous subtypes.  But every case of cancer is literally a different disease in a very real sense, and indeed, within one person, a single cancer can become, effectively, more than one disease.

We each* start out as a single fertilized egg cell, but by adulthood, our bodies have tens of trillions of cells, a clear demonstration of the power of exponential expansion.  Even as adults, of course, we do not have a static population of cells; there is ongoing growth, cell division/reproduction, and of course, cell death.  This varies from tissue to tissue, from moment to moment, from cell type to cell type, under the influence of various local and distant messengers, ultimately controlled by the body’s DNA.

Whenever a cell replicates, it makes a copy of its DNA, and one of each copy is sent into each daughter cell.  There are billions of base pairs in the human genome, so there are lots of opportunities for copying errors.  Thankfully, the cell’s proofreading “technology” is amazingly good, and errors are few and far between.  But they are not nonexistent.  Cosmic rays, toxins, other forms of radiation, prolonged inflammation, and simple chance, can all lead to errors in the replication of a precursor cell’s DNA, giving rise to a daughter cell with mutations, and when there are trillions of cells dividing, there are bound to be a number of them.

The consequences of such errors are highly variable.  Many of them do absolutely nothing, since they happen in portions of the genome that are not active in that daughter cell’s tissue type, or are in areas of “junk” DNA in the cell, or in some other way are inconsequential to the subsequent population of cells.  Others, if in just the wrong location, can be rapidly lethal to a daughter cell.  Most, though, are somewhere in between these two extremes.

The rate of cell division/reproduction in the body is intricately controlled, by the proteins and receptors in that cell, and the genes that code for them, and that code for factors that influence other portions of the genome of a given cell, and that make it sensitive or insensitive to hormonal or other factors that promote or inhibit cell division.  If a mutation in one of the regions of the cell that is involved in this regulatory process—either increasing the tendency to grow and divide or diminishing the sensitivity to signals that inhibit division—a cell can become prone to grow and divide more rapidly than would be ideal or normal for that tissue.  Any given error is likely to have a relatively minor effect, but it doesn’t take much of an effect to lead to a significant increase in the number of cells in a given cell type eventually—again, this is the power of exponential processes.

A cell line that is reproducing more rapidly will have more opportunities for errors in the DNA reproduction of its many daughter cells.  These new errors are no more likely to be positive, negative, or neutral generally than any other replication errors anywhere else in the body, but increased rate of growth means more opportunities** for mistakes.

If a second mistake in one of the potentially millions (or more) of daughter cells of the initial cell makes it yet more prone to divide rapidly than even the first population of mutated cells, then that population will grow and outpace the parent cells.  There can be more than one such daughter populations of cells.  And as the rate of replication/growth/division increases in a given population of cells, we have an increased chance of more errors occurring.  Those that become too deleterious will be weeded out.  Those that are neutral will not change anything in the short term (though some can make subsequent mutations more prone to cause increased growth rates).  But the ones that increase the rate of growth and division will rapidly come to dominate.

This is very much a microcosm of evolution by natural selection, and is a demonstration of the fact that such evolution is blind to the future.  In a sense, the mutated, rapidly dividing cells are more successful than their more well-behaved, non-mutated—non-malignant—sister cells.  They outcompete for resources*** against “healthy” cells in many cases, and when they gather into large enough masses, they can cause direct physical impairments to the normal function of an organism.  They can also produce hormones and proteins themselves, and can thus cause dysregulation of the body in which they reside in many ways.

Because they tend to accumulate more and more errors, they tend to become more dysfunctional over time.  And, of course, any new mutations in a subset of tumor cells that makes it more prone to divide unchecked, or that makes it more prone to break loose from its place of origin and spread through the blood and/or lymph of the body will rapidly become overrepresented.

This is the general story of the occurrence of a cancer.  The body is not without its defenses against malignant cells—the immune system will attack and destroy mutated cells if it recognizes them as such—but they are not perfect, nor would it behoove evolution (on the large scale) to select for such a strictly effective immune system, since all resources are always finite, and overactive immunity can cause disease in its own right.

But the specific nature of any given cancer is unique in many ways.  First of all, cancers arise in the body and genes of a human being, each of which is thoroughly unique in its specific genotype from every other human who has ever lived (other than identical twins).  Then, of course, more changes develop as more mutations occur in daughter cells.  Each tumor, each cancer, is truly a singular, unique disease in all the history of life.  Of course, tumors from specific tissues will have characteristics born of those tissues, at least at the start.  Leukemias tend to present quite differently from a glioblastoma or a hepatoma.

Because of these differences, the best treatments for specific cancers, even of classes of cancers, is different.  The fundamental difficulty in treating cancer is that you are trying to stop the growth and division—to kill—cells that are more or less just altered human cells, not all that different from their source cells.  So any chemical or other intervention that is toxic to a cancer cell is likely to be toxic to many other cells in the body.  This is why chemotherapy, and radiation therapy, and other therapies are often so debilitating, and can be life-threatening in their own right.  Of course, if one finds a tumor early enough, when it is quite localized, before any cells have broken loose—“metastasized”—to the rest of the body, then surgical removal can be literally curative.

Other than in such circumstances, the treatment of cancer is perilous, though not treating it is usually more so.  Everything from toxic chemicals to immune boosters, to blockers of hormones to which some cancers are responsive, to local radiation are used, but it is difficult to target mutated cells without harming the native cells to at least some degree.

In certain cases of leukemia, one can literally give a lethal dose of chemo and/or radiation that kills the bone marrow of a person whose system has been overwhelmed by malignant white blood cells, then giving a “bone marrow transplant”, which nowadays can sometimes come from purified bone marrow from the patient—thus avoiding graft-versus-host diseases—and there can be cures.  But it is obviously still a traumatic process, and is not without risk, even with auto-grafts.

So, as I said at the beginning, there is not likely to be any one “cure” for cancer, ever, or at least until we have developed technology that can, more or less inerrantly, recognize and directly remove malignant cells.  This is probably still quite a long way off, though progress can occasionally be surprising.

One useful thing cancer does is give us an object lesson, on a single-body scale, that it is entirely possible for cell lines—and for organisms—to evolve, via apparent extreme success, completely into extinction.  It’s worth pondering, because it happens often, in untreated cancers, and it has happened on the scale of species at various times in natural history.  Evolution doesn’t think ahead, either at the cellular level, the organismal level, or the species/ecosystem level.  Humans, on the other hand, can think ahead, and would be well served to take a cue from the tragedy of cancer that human continuation is not guaranteed merely because the species has been so successful so far.

Anyway, that’s a long enough post for today.  I won’t address matters of Parkinson’s Disease or Alzheimer’s now, though they are interesting, and quite different sorts of diseases than cancers are.  I may discuss them tomorrow, though I might skip to Friday.  But I am again thankful to StephenB for the suggestion/request, and I encourage others to share their recommendations and curiosities.  Topics don’t have to be about medicine or biology, though those are my areas of greatest professional expertise.  I’m pretty well versed in many areas of physics, and some areas of mathematics, and I enjoy some philosophy and psychology, and—of course—the reading and writing of fiction.

Thanks again.

*I’m excluding the vanishingly rare, and possibly apocryphal, cases of fused fraternal twins.

**There are also people who have, at baseline, certain genes that make them more prone to such rapid replication, or to errors in DNA replication, or to increased sensitivity to growth factors of various kinds, and so on.  These are people who have higher risks of various kinds of cancer, but even in them, it is not an absolute matter.

***Most tissues in the body have the inherent capacity and tendency to stimulate the development of blood vessels to provide their nutrients and take away their wastes.  Cancer cells are no exception, or rather, the ones that are do not tend to survive.  Again, it is a case of natural selection for those cell lines that are most prone to multiply and grow and gain local resources.

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The borogroves sure are mimsy today, aren’t they?

It’s Friday again, and another weekend approaches.

Yippee.  Huzzah.  O frabjous day.

I think I don’t work tomorrow—at least, I’m not supposed to—so there probably won’t be any blog post then (which will be Saturday, unless some hitherto unimagined catastrophe literally throws the days of the week out of order).

I may be posting a new video on my YouTube channel this weekend, though.  I haven’t made one yet, so there’s no guarantee that something won’t stop me from doing so.  I’m unlikely to be lucky enough to be involved in an asteroid impact between now and tomorrow, but there’s a functionally limitless number of things that could, in principle, stop me from recording a video.

Nevertheless, it is my intention to make a video, so I probably will.  This is a different type of thing than fasting; no physiological processes and neurological feedback loops are likely to interfere with my commitment to making a video.  Evolution is, so far, utterly blind even to the existence of videos…though that could change.

I’m still not sure what topic I want to address in the video, unlike last time.  I may literally just start my timer, start my video, start to talk, and see what happens.  If that sounds like an inauspicious way to start a video, well, you’re reading the written equivalent of it right now.  If you enjoy this, you’re proof that it can work.  If you don’t enjoy it, that’s not proof that it cannot work, since your lack of enjoyment doesn’t preclude anyone else from enjoying it.

People do seem to have trouble understanding that others can like things that they themselves find disgusting.  I can sympathize with that, and fall prey to the failing myself, but that doesn’t make it reasonable.

It’s true that all mammals, let alone all humans, have more in common than they have differences, but nevertheless, the potential differences just within a given species, given sexual recombination of genes and the sheer number of genes each individual has, is well worthy of the adjective “astronomical”, so we shouldn’t be surprised that others like things we find repugnant.  In fact, given that the number of possible combinations of gene pairs in human DNA alone is vastly larger than the number of (for instance) light years the visible universe is across*, maybe we should switch our use of the terms “biological” and “astronomical” to describe very large numbers.  Unfortunately, I think most people wouldn’t catch onto the nuance of saying that something was “biologically large”.

Oh, well.  It was a brief dream, swiftly shattered by the one who dreamed it.  Typical.

Anyway, so, I’m back on food again, more’s the pity.  I’m tired of having all these biological urges and needs and drives.  They’re very irritating.

Also, I’m tired of how stressed and angry I get about things people do at work.  Don’t get me wrong—the specific things I’m thinking about are worthy of anger.  But the problem is that I get so stressed, and so angry, and it just makes me hate myself more and more all the time, without any evident upper bound to the process.

I wish it were true to say, “I can’t stand it anymore”, but unfortunately, I’m able in principle to continue standing things for who knows how long.  I wish I would just collapse into a heap, and literally, physically, not be able to go on.  It would take so much out of my hands and would be such a relief.  Unfortunately, there’s no clear sign of that happening, though I try to sabotage my own health as much as feasible without being Baker Acted.

And here is another maddening thing that just happened:  the trains this morning, it turns out, were all shifted to one side of the track, as was the case last week once.  But this wasn’t announced early, unlike last time, so I went to my usual spot to start writing this while waiting.  Then, when the “announcement” was made, it was just posted on the overhead light board; there was no verbal announcement, though they give recorded verbal reminders about such things usually—they’ve been informing us, ever since Labor Day, that the system will be running on a Sunday schedule on Thanksgiving, which is in November, for those of you who don’t know.  Labor Day was in the beginning of September.

I only failed to miss my train because I always start getting ready to board five minutes early, and I looked up from my writing to notice that there was no one on my side of the tracks.  Only then did I see the notice that trains were all boarding on the other side.  I was able to take the elevator up to the bridge, but I had to rush down the stairs on the other side because my train was approaching, and my knees and hips and ankle were miffed about that.

It would have been nice for one of the people who always gets on the same train I get on to have said something to me, rather than just letting me sit there typing on one side of the track by myself.  I’d like to think I would have said something to them, were the situation reversed.  Maybe I wouldn’t.  Maybe it’s an instance of the bystander effect.  Maybe it’s one of those rare circumstances in which my reticence to interact with strangers is obvious to everyone, and I seem so unpleasant that no one wants to interact with me even enough to say, “Hey, all the trains are boarding on the other side for some reason…better cross over.”

Better cross over.  That’s the best idea I’ve heard today, that’s for sure.

Okay, well, that’s it for today’s disjointed meandering.  I hope you’ve found some modicum of joy in it.  It would be nice to be able to do at least something positive for the world, even if it’s small.  It would be far better than what I usually do.

*Using the particle horizon as the measured “distance across”. **

**Actually, since there are four bases in human DNA (guanine, cytosine, adenine, and thymine), if they were assigned randomly, then even a string of 1000 base pairs has 1.15 x 10602 possible combinations.  If memory serves, this is larger than the String Theory landscape, which number is already so vast as to lead many physicists to say it can predict anything and therefore it can predict nothing.  And human DNA is on the order of a billion nucleotides long.  My computer calculator can’t deal with billionth powers of four, but a billion is a thousand times a thousand times a thousand, so 41000 cubed should be about 101806 unless I’m missing something.  The diameter of the visible universe in Planck lengths is only 5 x 1061, which is not even close to the same order of magnitude.  Of course, the maximal information within a horizon the size of the visible universe is larger still, but then again, that’s a measure of the maximum entropy possible within that region, so that’s almost a given.  I think it’s 210^123 or something along those lines.  I may be getting at least some of this wrong.

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Welcome to the October Country

Well, it’s October 1st, the beginning of a new month in 2022, a month initially meant to be the eighth month, based on its name.

I’m at the train station and, it being Saturday, the schedule is different than during the week.  There’s also some question of whether the trains are boarding on the usual side or not.  There’s a displayed “announcement” on the light boards that all trains are boarding on one side at this station until further notice, but it could be something left over from yesterday.  Also, the guard is not aware of anything regarding the change in sides.

Nevertheless, today was a day for ordering the monthly pass on the machines, and the ones on my usual side weren’t even working, so I’m on the other side for the moment, anyway.  I’m going to have to try to be vigilant as the time for my train approaches*.  If I miss one train, the next won’t come for another hour.

It’s hard to be vigilant, though.  I feel absolutely exhausted.  My brain feels like it’s barely running on one cylinder, metaphorically speaking**.  I’m just so very tired.

Thankfully, I can embed below my video, which I did end up posting on my YouTube channel yesterday afternoon, so that can provide some of the content and spare me a little writing today.  I might as well, since what I’ve written so far is about some of the most banal things imaginable.

Just a bit of clarification about the video, in case any is necessary:  Obviously I don’t mean to say there is literally no life in the universe, since that would be a contradiction (If there were literally no life, then I could not be speaking about the fact).

I just have always been irked by people who make the wide-eyed claims that it’s so amazing and quasi-mystical that the constants of nature are so perfectly designed to make life, and that must imply some sacred meaning or purpose to it.  That’s about as idiotic as looking at the location of a speck of dust in the corner of a school gym and saying how amazing it is that all the facts of nature conspired to bring that speck of dust right there at that point…it had to have been part of some greater purpose!  It’s drivel.  Only the case with life is even more unimpressive.

My biggest issue with this is that it leads to a kind of quiescence, an assumption that, if the universe was “designed” just so that life can exist, then life, and particularly intelligent life, must be important, and the universe will somehow arrange things to nurture us and protect us from extinction.  If you think that’s the case, then ask the dinosaurs, or better yet, any of the far greater numbers of life forms that went extinct in the Permian-Triassic “Great Dying”.

Oh, wait, you can’t.  They’re all extinct.

No, the universe is almost completely hostile to life, both in terms of its space and in terms of its time.  We are lucky beyond ordinary imagining, though I tried in the description of the video to give some notion of just how lucky in spatial terms, at least, by noting that life exists in roughly only 1.5 x 10-64 of the universe’s volume.

As far as time goes, well if you’re thinking of humanity alone, based on the time that has elapsed since the “Big Bang”, which may or may not be the literal beginning of our universe, the percentage is tiny enough, and others have demonstrated this handily, as in the “cosmic calendar” that Carl Sagan made famous in Cosmos.  But if you want to count all expected possible future time, well then our existence is some fraction of what could be infinity, which is pretty undefined, but might as well be called zero.  The limit certainly approaches zero as we extend the future further and further.

This is not necessarily a call for people just to give up and say “what the hell”, though you have that option, of course, and it is tempting.  I wanted to note that, if you would like for life to continue, and even to have some lasting, cosmic-scale impact, then you can’t take it for granted.  You need to work at it, and work hard, and work long.  The universe is not trying to kill us (contrary to Neil DeGrasse Tyson’s habitual way of putting it); if it were, we would be dead already.  But the universe is huge, and it does not even have the capacity to care what happens to life, except in the minds of that life itself.

All life is in the situation of a castaway on a desert island—there’s no preexisting infrastructure, there’s no one out there looking out for you or protecting you, or providing your light, your heat, your air-conditioning, your food, your clothes, your shelter, what have you.  If you want any of those things, you’re going to have to make and/or find them for yourself, and you’re going to have to keep doing it, for as long as you actually want them and want to survive.

Without much more ado, here’s the video***.  I forgot to ask when I made the video, but please give a “thumbs up” and subscribe and share if you are at all inclined to do so, for any colorable reason.  And feel free to check out the other stuff on my YouTube channel if it looks interesting to you.  If anyone finds this interesting at all, I’m hoping to make more such videos about topics that interest me, assuming the universe doesn’t eliminate me in the meantime (though it seems likely to do so).  Oh, and please let me know what you think, either in the comments below the video or here.

Thanks.  Here it is:

*Just a slightly later addendum:  They have announced overhead that my train is approaching in 10 minutes, and have confirmed that it is not on its usual side.  So I was right to be proactive.

**Of course, it’s a metaphor.  I don’t honestly think that any of you really believe that my brain is an internal combustion engine of some kind, except in the loosest of possible senses.  Apologies.

***I wore a mask and dark glasses in the video mainly because I don’t like how my face looks—it bears evidence of the many things that have happened to me in the last decade or so.  Maybe no one else can see it but me, but it is what it is.  Anyway, the glasses are awesome, I really like them, and the mask combined with them makes for a good look, I think.  Certainly better than my underlying face, anyway.