Details Matter

Seen during our last day on Maui. Evidently we missed the beheading? The prints in the sand suggest a dog was involved. We paused briefly, cringed, then moved on.

Back in Anchorage, at the dog park. If I recall correctly, I snapped a photo here sixteen years ago and made it the wallpaper on my lab computer, so I’d never forget how simply serene it is. It still is. Except the one big change we noticed since returning in 2009 is the number of trees felled by beavers, mostly near water’s edge, but also at certain spots around the lake quite a ways up the bank. And it’s not only trees, them beavers can wreak havoc on dogs caught swimming in the lake. Not so serene then.

Anchorage is opening up. The Goodthinkers at City Hall say the vaccinated among us may now move about nearly everywhere sans masks. And why not? Because the vaccine is 95% effective at preventing infection from Sars-CoV-2 (the details are important, keep reading), what difference does it make if there are cheaters among us, i.e. people who are not vaccinated and won’t wear a mask. That should concern other cheaters, but of course there’s a simple (and free) way for them to solve that problem, get vaccinated. That way you can sit right next to me at Suite 100 and enjoy a grilled fillet of Copper River King salmon over a garlic mash, with of medley of veggies, worry free. And if I’m feeling generous, I may even buy you your first glass of Cabernet, as a thank you for your contribution to herd mentality immunity. Win win.

I see signs around town advertising Covid-19 tests, the PCR kind!. Funny how the pandemic has established PCR in the modern lexicon. Even though most people will have no idea what it means (Polymerase Chain Reaction), how the test works, or any of that. Why should they? The technology most of us use day to day, we have no idea how it works. It takes me half a class period to explain to genetics students how PCR works. And they come to class with a basic understanding of DNA, if they’ve done their homework and attended lectures that is. But students aside, the average person doesn’t understand what DNA is, much less how it’s analyzed in a PCR test. All they need to know is that a negative PCR test for the virus avoids a ten day quarantine when they arrive in Hawaii. And who even cares how an exhaust emission test works, all I want is a Pass score on my car to fast-track it through registration, to avoid the dreaded visit to the DMV.

Imagine instead that before you could use a technology you had to prove you understood the basics of how it worked. Imagine the proof involved explaining to a child in the most basic of terms how a toaster works, how a combustion engine works, how a text message gets from one phone to another (it’s fascinatingly complicated). A close friend of mine once posited that if the average modern were sent back in time to the 17th century, well before the first chemical battery was invented, and had to explain to a renaissance scientist what a battery is and the basics of how it works, your average time-traveler would have no clue.

As a practical matter it makes no difference to most people how things work. If you want a crisp bagel you slide the two halves into the toaster slot, depress a handle, and wait. You don’t need to understand how a combustion engine works to drive a car, or how the “I love You” emoji gets to your wife’s phone, it just works, don’t ask me how. If you want to know the implementation details of how pretty much anything works in atomic detail, you need to educate yourself. This takes time – often a lot of time – and hard work. There are very few short cuts.

Most people don’t know (or even care enough to want to know) how Ibuprofen relieves pain, you just pop 800 mg into your mouth, wash it down with water and wait. For a long time I was one of those people. Then, in 2000, while living and working in Santa Fe, after having become disillusioned with the kind of work I was doing there, and had done for many years prior, along with the prodding of a close friend to break away from that to do something that interested me, I revisited my nerd-like interest in how drugs worked – and by interest I mean the actual implementation details of how they work, at the level of biochemistry.

Such learning takes time and commitment. And if I was going to do it, and succeeded, maybe I could parlay all that learning into a new career (though I didn’t give that part nearly enough thought). So off I went to get a PhD in Pharmacology, in the company of a woman soon to become my wife and two jug-headed dogs. None of them were too keen on leaving Alaska.

Fast-forward sixteen years. Have you ever thought about how THC makes you feel high (or for that matter what THC is)? I think I know now! Or even wondered more deeply about alcohol? Like why does the addition of a single carbon atom to methanol (C-OH), itself a very lethal compound, create a new alcohol called ethanol (C-C-OH), which doesn’t kill you, but instead merely makes you drunk (notwithstanding lethal doses, relatively rare among drinkers). Add another carbon and you get propanol, similar to ethanol in how it effects humans, but much more potent and more likely to be lethal. Add still more carbons to the chain, or change the order of how atoms connect (who knew stereo-chemistry was so important!), and the alcohol’s properties get even more weird.

Ever wonder why drugs have so many side effects? Some can be severe. For example, listen to the mellifluous voice on any TV ad pitching a new drug (call it, Euphorimab) – “Euphorimab may cause stroke, internal bleeding, or complete loss of appetite. If you lose consciousness or die after taking Euphorimab, please notify your doctor immediately.” Ha ha, funny, right? But all kidding aside, do side effects occur because drug company scientists don’t really know how the drug works, the implementation details? No. The bar for approval of a drug is actually pretty high, usually including proof of the molecular mechanism of action of the drug. There are exceptions*. Before a drug is approved scientists must provide considerable experimental evidence that shows Drug X modulates (inhibits or activates) a specific protein known to be causative in whatever malady it was designed to alleviate. But there remain two big challenges in drug development 1) Many of these “target” proteins occur in different parts (tissues) of the body, and 2) many drugs are promiscuous, in the sense that they have unexpected, off-target activities in the body. Meaning the drug can bind to and modulate proteins it wasn’t designed to target.

* A class of drugs known as volatile anesthetics are a notable exception to the rule. They’ve been used to anesthetize patients starting 160 years ago, before the FDA took on its regulatory approval function. They’re still approved for use in patients undergoing surgery even though nobody knows how they work at the molecular level. You’d probably get a Nobel prize if you could figure it out. I once rotated in the lab of an anesthesiologist (and pretty good geneticist) who was trying to figure it out. We never did figure it out but we killed a lot of worms trying.

Example: Vicodin is (or was) a widely prescribed narcotic active in the central nervous system to alleviate musculoskeletal pain. But for a lot of people it also makes them very drowsy, nauseous, and constipated, some severely. Mood swings and poor judgement are not uncommon side effects.

Scientists are pretty certain Vicodin works by binding to and modulating a class of proteins called mu-opioid receptors. Activating these receptors in the central nervous system has the downstream effect of inhibiting the brain’s pain response circuit, but at the same time activating certain reward pathways in the brain (the reason for opiate addiction). But these receptors occur in other places in the body too; one of which is – believe it or not – the gut. The gut doesn’t do the thinking or pain processing in the body, that’s the brain’s job, so what are these receptor proteins doing expressed in the gut? Answer: it’s all about context. Tickling mu-opiod receptors in the gut (versus the brain) with a dose of Vicodin triggers them to “signal” back to the brain, via the nervous system, that something is out of whack down here. That in turn generates another cascade of effects, also mediated by the nervous system, which end in the feeling of nausea in the gut, and often a backup of poop. So, generally speaking, depending on which tissue a protein is expressed in, different (unintended) side effects may occur after a drug binds to it.

The other cause of side effects, drug promiscuity (so-called “dirty drugs”), is much harder to deal with. As mentioned, drug approval usually requires experiments to prove how a drug works at the molecular level, and in turn how that will reduce disease (or pain, etc.). But selective experiments can’t detect if the drug is also active against other protein targets. It’s only after the drugs get into real patients that the side effects of “off-target activities” are discovered, and the corresponding proteins/pathways identified (sometimes). Certain chemotherapy drugs, for instance, are notorious for off-target effects – hair loss, severe fatigue, constipation, vomiting, weight loss, bleeding, muscle & joint pain, etc. (Can you hear that voice on the TV ad?).

Wait, don’t we have precision medicine now? Can’t you design a drug that targets only a single protein? Yes, but it’s damn difficult. Gleevec is the best example I can think of. It’s used to treat certain types of leukemia. It was designed to target a mutant protein (oncogene) produced in patients with a specific chromosomal aberration. It took many scientists working many years to characterize the molecular details of this aberration, and then more years to design a specific drug to target it. Think about how difficult it would be, and how long it would take you, to make a key for a lock you can’t see with the naked eye, and can only model (in 3-D) using indirect experimental evidence.

OK, I’m rambling. The point is, drugs are really just another kind of technology. And, like most other technologies one people don’t need to understand the details of in order to benefit from. Coming to know the details, on the other hand, if you’re curious like I was, will convince you just how freakin’ complicated biology really is.

Some Time Away

By day we awake to this
By night…
Happy hour at the Seahouse
A visitor arrives. A red-crested cardinal it appears. Sorry fella, we were ordered not to feed you.
For dinner…Island-made crab cake with sweet chili sauce, homemade Tabouli salad, fresh Ono and asparagus grilled, served over a bed of Gazebo fried rice

MvS Was Right, Hope I Am Too

With Covid defeated (we’ve been vaxed) we tripped up to Fairbanks (aka Squarebanks) recently for a long overdue visit with family. The flights to and from were uneventful and Alaska Air even upgraded us to first class both ways. That’s Happy Wife’s brother on the right, his bride rear center with the peace sign flanked by their two daughters. They live in a cavernous log home brother Mike chinked himself way back when. We ate lots, drank too much, played board games and walked the trails around the property. They experienced epic snowfall up there this year so you had to be careful not to step off the trail lest you sank in up to your waist.

Their daughters are a delight to hang with. One is off to the U of Montana come Fall, the other is still in high school. They’re both smart as a whip. The younger daughter does math for fun. Being reminded of that we got off on the topic of the Monty Hall problem. Actually, I think it was one of the girls who brought it up. A long time ago in a magazine a reader posed a question to Marilyn vos Savant, aka MvS (smart as a whip herself):

Suppose you’re on a game show, and you’re given the choice of three doors: Behind one door is a car; behind the others, goats. You pick a door, say No. 1, and the host, who knows what’s behind the doors, opens another door, say No. 3, which has a goat. He then says to you, “Do you want to pick door No. 2?” Is it to your advantage to switch your choice?

Marilyn replied the contestant should always switch because doing so gives the contestant a 2/3rds chance of winning. Most people, even really smart people, loudly disagreed with her. Duh, they said, obviously with only two doors left there’s a 50/50 chance of being right, i.e. picking the door with the car.

Showoff Marilyn stood her ground, calmly explained why she was correct in a follow-up comment, but still many people couldn’t bring themselves to accept the truth. In fact, pose this same question to people today and many will insist the answer is 50/50.

Back to our conversation… turns out the girls were also in disbelief, though being smart as whips were interested to hear my take on it. I admitted to being among the disbelievers when I first heard this problem. Then, after doing my homework, came to understand why MvS was correct. I diagrammed the problem for the girls on paper, assigned the initial probabilities to the car being behind each door (trivial), randomly picked a door to start a game, then revealed one of the goat doors as Monty Hall always did. I then showed them why the probability of the car being behind the remaining un-chosen door is 2/3rds, not 50/50. Good diagram here.

You could see on their faces the light go on! Notice that switching doesn’t mean the contestant is sure to win, only that on average, over repeated games, doing so wins the car 2/3rds of the time. The only way you lose with this strategy, of course, is if the car is behind the door you initially selected.

When we got back home I wrote a simulation to once again prove to myself MvS was right. Here’s the code (Java)

import java.util.concurrent.ThreadLocalRandom;

public class MontyHallSim {
	private int goats[] = new int[2];
	private int prizedoor ;
	private int guessdoor ;
	private int goatdoor;
	private int revealdoor;
	private int Rand(int min, int max) {
	  return ThreadLocalRandom.current().nextInt(min, max + 1);
	private void Guess() {
	  guessdoor = Rand(1,3);
	private void Seed() {
	  prizedoor = Rand(1,3);
	  if(prizedoor == 1) {
           goats[0] = 2;
	   goats[1] = 3 ;
	  } else if (prizedoor == 2) {
	   goats[0] = 1;
           goats[1] = 3 ;
	  } else {
	    goats[0] = 1;
	    goats[1] = 2 ;
	private void Reveal() {
	  int goat = Rand(0,1); // random index into goats array 
	  revealdoor = goats[goat] ;
	  if(revealdoor == guessdoor) {
	    revealdoor = goat == 0 ? goats[1] : goats[0] ;
	  goatdoor = revealdoor == goats[0] ? goats[1] : goats[0] ;
	private double Run(long games) {
	  long wins = 0 ;
	  for(int i=0;i<games;i++) {
            Seed() ; // randomize goats and prize behind doors
	    Guess(); // randomize contestant's guess
	    Reveal(); // Monty reveals a goat door
	    wins += guessdoor == goatdoor ? 1 : 0; // switch & win!
	    return (double)wins/(double)games ;
	public static void main(String[] args) {
	  long ngames = 300000000 ;
	  double prob = (new MontyHallSim()).Run(ngames) ; 
	  System.out.println("Probability of winning if you switch       
          (n=" + ngames +"): " + prob*100.0 + "%") ;

Compile that and let ‘er rip on your computer, say three hundred million times (see ngames value). Guess what the output is?

Why, it’s precisely what MvS said it would be

Probability of winning if you switch (n=300000000): 66.665%

Moral of the story: Never bet against MvS.

What fascinates me is how counterintuitive the right answer is. Way back when I first encountered the problem I was like no way.

Late last week then we hosted our first dinner party in over a year

HW spent all day and part of the night before making a truly delicious Coq au Vin, served over Polenta with a side of grilled bread. That last was the only part I was directly involved with, except I did have the forethought to de-cellar what turned out to be a sumptuous 2007 Amarone from one of my favorite producers.

Those are our dear friends we did that crazy Pittsburgh –> DC bike ride with a couple years ago. All of them are retired. Being we’re next in line to reach that milestone (ever so close) I pick their brains all the time. I’ve been working tirelessly pulling together a spreadsheet of information I need to do predictive financial planning for the next thirty years of life (fingers crossed). Because, as our financial advisor says, “Rod, a goal without a plan is merely a wish.” She’s right of course. So, god willin’ and the creek don’t rise it looks like we’re all set to go. I spend at least a half-day each weekend spinning what-if analyses in the spreadsheet. Even with conservative estimates of all the relevant variables (SS, ROI, etc.), and a very generous annual spending budget, we will likely leave money on the table when we exit this life. I don’t yet know how I feel about that prospect, compared to the alternative that is. Though I’m sure our beneficiaries will be thrilled!

Too bad MvS isn’t still with us, I’d ask her opinion.

Careful What You Ask For

Open water in February, spotted along the trail while out with The Dog. We encouraged him to step in for a drink, he refused, being he’s kinda wary of the unfamiliar. It was his first time on this trail.

For over thirty years Happy Wife and I have walked, hiked, biked and skied with dogs on trails all over the Anchorage bowl. There must hundreds of them. Usually the dogs are off leash, with certain exceptions (e.g. when moose or porcupines are about). Recently, there was a kerfuffle in the opinion section of our local newspaper over off-leash dogs on the trails. The outrage bubbles up every five years or so. The existing ordinance says all dogs must be leashed on the trails, except for dogs under voice control or those wearing some kind of electronic collar. Certain “activists” about town want the ordinance strengthened, such that every dog must be on a leash on every trail (except in designated off-leash dog parks), and they want animal control to step up enforcement.

Full disclosure: even under the current ordinance we are technically out-of-law. We don’t now, and never have, put an e-collar on our dogs, and coming when called has never been their strong suit, especially the Airedales. What has been a feature of all our dogs is non-aggression, certainly towards uprights, but also towards other dogs. I simply won’t stand for an aggressive dog in my company.

Again, we’ve enjoyed the trails in this way for over thirty years. We’re not alone. There are hundreds of trail users doing the exact same thing with their dogs, peacefully minding their own business and dealing with infrequent conflicts where they arise. If there were a crisis number of conflicts with dogs out there we’d know about it by now. There is no problem to solve. And even if there was, if it hasn’t been solved by the existing ordinance it won’t be solved by a stronger version. More on this below.

So what’s the clamor this time? Nothing new really.

The reasons cited in the comments to the op-ed were: “I’ve been bitten by so many dogs on the trails I’ve lost count!” or “I’ve been knocked off my mountain bike countless times when a loose dog has run in front of me!” or “The mountains of poop not picked up by irresponsible dog walkers are polluting our streams, causing disease, and it makes me sick to look at it!

This kind of lame reasoning annoys me. If you’ve been bitten so many times you’ve lost count, I’m sorry you’re a magnet for dog aggression, but please don’t make my dog and the hundreds (thousands?) of other non-aggressive dogs the target of your activism.  And bikers, please slow down and be aware of sudden changes on the trail. As an avid cyclist myself I understand the importance of trail ethics. Next time it may be an alacritous child who darts out in front of you. Should they be leashed too? Remember: these are multi-use trails – get it, Multi-. Oh, and the poop complaint, trust me, leashed dogs poop too.

And one more thing: As anyone who has used the trails as much as we have knows, dogs on a leash pose a greater obstacle to other trail users (runners, bikers, etc.). It makes it much more difficult to go around when leashes are extended across the trail. And as dog people will tell you, leashed dogs tend to exhibit more aggression compared to unleashed dogs. So aiming your ordinance at unleashed dogs, to get them “under control” to increase the net safety of all trail users, may actually make the perceived problem worse.

Alas, here’s a vignette from the comments section of the op-ed, where pointing any of this out can get you smeared as a no-good scofflaw – scofflaw?! – or chided as some kind of closet anarchist who doesn’t believe the law applies to them 🙄

Who knew the simple activity of walking a harmless dog off leash on a trail, as we have for three decades, actually poses as big a risk to public safety as a red light runner! And down the moral rabbit hole we go…

Tom says:

“Under voice command” is not the (current) law, so you are a selfish scofflaw. Can you run red lights because your car is under your command?

I reply:

Tom, if a trail user steps off the trail to pee, is she an irresponsible trail user, and/or a selfish scofflaw? If a cyclist has not registered his bike with the city or has not clearly marked it as such, is he an irresponsible trail user and selfish scofflaw? If so, by all means, help us identify these individuals so we know where to send the fine(s).

Another reply to Tom by Shawn (no doubt another scofflaw):

I love all these holier than thow people on here, because im sure you obey all traffice laws, bikers never break rules either, skiers always ski in control, i mean get serious. If his dog is not attacking anyone and is behaving who cares? There is no room for well behaved dogs because of bad behaved dogs?

The loopy “logic” of people like Tom makes it clear to me and others this has nothing to do with off leash dogs threatening public safety. That’s a joke. Has a dog never bitten a trail user? Of course it has, and there are existing laws that give the victim recourse, if need be. More likely the conflict is resolved by the parties involved. I know, one of my dogs years ago was badly injured when another dog attacked it on the trail, unprovoked. The dog’s uprights were appalled and did everything possible to make sure I sent them the vet bills. So yes, shit happens. Point is, it’s rare, really rare. Camaraderie rules the day. Something you might appreciate if you’d used the trails regularly for, oh, I don’t know, maybe thirty years or more?

What this is really about is a special-interest minority of trail users who 1) don’t like dogs, period, and/or 2) want to limit other trail user’s activities to favor their own. Combine that with an officious-minded worldview and you get activists weaponizing ordinances.

These are multi-use trails the city is obliged to maintain for the benefit of all of users – skiers, bikers, skateboarders, roller bladers, tourists, stroller pushers, and yes, dog walkers. And of course your criminal element is out there as well –  many of the trails run through heavily wooded areas. Illegal drug use and physical assault, even murder, are unfortunately not unknown. But let’s not talk about that. No, the real bugaboo to public safety is unleashed dogs 🙄

Nothing will change on the trails, passage of the ordinance or not. The existing one hasn’t been enforced. Never in thirty years have I been stopped by an animal control officer and ordered to put my dog(s) on a leash, not once. The state is broke, the city is broke, there’s no money for increased enforcement. Crime in the city (including on the trails) is increasing. Why make more criminals with a new ordinance?

The Problem with Countrymen

Back in October of 2019, Happy Wife and I along with two other couples bicycled from Pittsburgh to Washington D.C. Part 1 was chronicled here. Somewhere near the halfway point of the ride, in southern Pennsylvania, the six of us hopped on a shuttle to go visit the Flight 93 memorial.

United Airlines Flight 93 was one of four planes hijacked by terrorists on 9/11. The flight manifest revealed a light passenger load, a feature of that particular flight which, among others, the terrorists preferred during their planning of the suicide missions – fewer passengers would mean less resistance, a lower chance of failure.

A lower chance, maybe, but fortunately not zero.

About forty minutes into Flight 93, now aware it had been hijacked by terrorists, some of the passengers stormed the cockpit door in order to break through and foil the terrorist’s plan. How? Exact details of what happened during the ensuing minutes are sketchy (the transcript from the recovered cockpit voice recorder was unclear at best), though pretty clearly wresting control of the plane from the terrorists had to be the first step. Once the terrorists in the cockpit were convinced the passengers would eventually breach the door (or maybe after they had), the pilot (Ziad Jarrah) initiated a rapid descent to crash the plane, knowing there was not enough time left to reach the intended suicide target.

Pause here a while to reflect on that.

Excluding the terrorists, there were 40 people aboard Flight 93, passengers and crew, 37 were Americans. All of them thought they were flying to San Fransisco that morning. At the memorial there is a multi-wall display showing a large photograph of each passenger and crew member, accompanied by a written narrative devoted to the details of their lives. I recall the six of us lingered there a long time, solemnly transfixed on the photos. Personally, I couldn’t get over just how ordinary many of these people were. And then to try and comprehend that such ordinary people could be suddenly thrust into unimaginable circumstances, all of them of one spirit and knowing they were likely going to die soon, to be able to concoct a plan for the most physically able among them to storm the cockpit to thwart the terrorist’s goal – to crash into the White house – I just couldn’t get my head around it. From where in the soul does that kind of courage come?

Twenty years later, instead of acting to protect it at all costs, even death, different Americans, craven ones, would storm and breach the White house. Simply to defile it, and to do who knows what other harm to their fellow countrymen inside. And then to return to your cozy little suburban home and smugly show “pride” in having taken part in it, as some self-described patriot? Disgusting.

To try and reconcile these two classes of Americans into any coherent concept of my fellow countrymen, for me is frankly impossible.

A photo I took outside the entry to the memorial

And another looking back at the memorial, near the debris field where Flight 93 crashed. The orientation of the walls was designed to align with the most likely path of the plane as it came over that hill. NTSB estimated its speed at 536 mph at the time of impact, 10:03 am. It left a crater over ten feet deep, fifty feet wide. The collision registered on area seismographs.

Could Never Happen Here

Yesterday gave us all a lot to think about. As I expect is true for many of you, I have tried to avoid making assumptions about the intent of the people who did this. I certainly understand how easy it is to paint them all as dangerous criminals who came to create mayhem and take hostage – or even kill – the people they believe are standing in the way of reversing the election. Of course, even if that was the real intent of the mob as a whole, the ultimate goal to change the election result would never have been achieved, Biden would still be declared the president, eventually.

On the other hand, nothing I witnessed on real-time news coverage, or saw in the reporting afterwards, could possibly lead me to conclude a benign intent of everyone involved. Pipe bombs and firearms were confiscated, and at least sixty people were arrested, people who likely (hopefully) will face serious criminal charges. Indeed, the more I think through this and read what others have written about it, I want to lean toward saying we simply don’t know enough now, and may never know enough, to speculate what the aggregate intent of the mob was, and thus what legal classification is correct. And maybe it’s pointless to even try.

What does seem to be clear is that this was a very disorganized mob lacking any coherent plan of execution or even a common notion of what the endgame was, or could be. And it’s equally clear that, to a one, these people were tRump idolaters, summoned by him via tweets to bring the fight directly to the White house. As such, I hold no sympathy for the supposed innocent ones hiding behind naivete, “We just came to protest, to make our voices heard, we didn’t want anybody to get hurt.” Really? In years past, lone gunman (real and imagined) have been shot on the White house lawn before even reaching the walls of the White house. The seriousness and consequences of that kind of trespass were made unambiguously clear in the days that followed. Yet you thought the actions to overcome security, occupy the steps right outside the front door, and remain there until your grievances were heard, would be met with, what, understanding? Really? (In fact, that is kinda what happened, but I’ll leave that for another post).

Protesters, rioters, criminal trespassers, insurrectionists, seditionists, terrorists – I don’t care to go down the semantic rabbit hole, though pretty clearly which one sticks will matter come prosecution and judgment time. But at the very least, unprecedented, misguided stupidity – yeah, I can get behind that.

Turning to something with more levity… had everyone in the mob been as freakishly harmless as this fella, I might judge them all as just hapless and misguided, deserving of our pity maybe. Seriously, give it a listen

One Percenter

The population of the United States is approximately 326 million. Vaccinating 80% of the population (the current estimate to reach herd immunity through vaccination) equates to roughly 262 million people. To date, 2.6 million people have received an initial dose of the vaccine (mostly the Pfizer version), i.e. about 1%. As of yesterday Happy Wife is in that count.

At this rate, reaching herd immunity via vaccination would take ten years. Clearly, a very different nationwide deployment model is going to have to be implemented if we’re going to “return to normal” by summer or fall of 2021.

Her Majesty

This was not here two days ago when we walked by. We asked others about it but nobody’s talking. The look ‘n feel is not otherworldly, not like the monolith in Utah (though I didn’t trudge through the snow to touch this thing – it kinda creeps me out). We’re going to keep an eye out and see what happens to it. It’s right off the path of one of our favorite low mountain hikes with The Dog, who issued his own wary, guttural growl as we passed by. Whether that was directed at the monolith or that brooding sky I can’t say.

It’s not always brooding. Even in our dimmest days it pays to look up now and then to take in the powdered treetops set against bluesky

This time of year in Anchorage it’s 10:30 am before Her Majesty rises over the Chugach mountains to paint the eastern sky, lately visible from the window in our new spa shower in the master suite

Pardon the items on the sill. Being the remodel was my idea, although with important design inputs from Happy Wife for sure, the spa has become a feature in the house that I, in a sense, am responsible for. This new role amuses Happy Wife to no end. Admittedly, I do tend toward over doing it when it comes to squeegeeing damp surfaces, keeping the grout tidy, hanging towels where they belong (ahem), etc. However, as I am wont to point out, “Important chores don’t complete themselves.” Also, I am a minimalist when it comes to the sundries of ablution. That is, I much prefer all such items be contained to the built-in shelf on the back wall of the spa. You know, the one I designed specifically to be used entirely and only for that purpose? Nevertheless, being I am not an unreasonable man, I have compromised my personal preferences in this matter to permit the pumice stone and soap dish a permanent place on the sill. Unsightly as it is, I’m sure you will agree.

Update: Since this photo was taken, I have insisted lovingly inquired of HW if she might find an alternative container for the soap – one consistent with her own sense of aesthetics, to be sure – to replace that ghastly bamboo soap dish that leaks goo out the bottom all over my otherwise spot-free sill! This request she granted, somewhat tersely, although without any real feelings of displeasure directed at me whatsoever. 😘

In certain places outside the home the caretaker role is often reversed. Especially where appointments of seasonal swag are concerned. The back porch, for instance, is HW’s domain. There you will find lights all twinkling, wreaths a-hanging, and this year no less than six luminaries a-glowing, homemade by HW herself. I sneaked the garden gnome (aka Norman) out of the house one night to photo-bomb the festive Feng Shui

Note that feral sky. I think we got hammered with like a foot of snow that night. Ho hum. All I know is we’ve turned the corner so far as daylight’s concerned. I’ve lived up here now the better part of thirty-one years. Winter solstice is my favorite “day” of the year, if for no other reason than it marks the return of Her Majesty, sloth-like yes, but eventually she never disappoints.

Recall: As usual on Rod’s Alter Ego, most photos may be embiggened with a simple click (or touch), which are then opened in a new tab.

Plug ‘n Play Molecular Biology

It interests me that both the Pfizer and Moderna vaccines exploit the same molecular biology to fight the novel coronavirus as the virus itself does to make us sick. You may have heard by now that these two vaccines are mRNA vaccines. mRNA stands for messenger RNA, the intermediate molecule between DNA and protein – DNA->mRNA->Protein – aka the Central Dogma.

The”active ingredient” of the virus is mRNA. It carries the instructions required to make more copies of the virus. But the virus can’t replicate itself, it first needs to get inside a human cell, break apart, and release the mRNA. From there, the cell recognizes the viral mRNA and translates it to proteins, specifically proteins required (in part) to create another viral particle. In a separate (more complicated) step, more copies of the viral mRNA are also made inside the cell. With all the required parts copied, in a final step they are re-assembled into a new virus particle which is effectively spit out of the cell (Exocytosis) to enter the circulation. From there the particle will infect more cells, make even more copies of itself, and so on. The point is, all of the hard work of replication is done inside your normal cells because they don’t recognize the mRNA as foreign. Detail

Stay with me now, almost there. Recall from above that an mRNA carries the instruction to make a protein. Also, as you’ve probably heard, the protein that enables coronavirus to enter your cells is the so-called spike protein – those pin-like protuberances sticking out of the viral particle’s shell (membrane). The spike protein is crucial to the virus’s ability to get into your cells. Unfortunately, your immune system can’t recognize the spike protein because it’s “cloaked” in other molecules, so no antibodies against the spike protein are produced that would bind to it and interfere with the virus’s ability to enter your cells. Fortunately, there are small pieces (peptides) of the spike protein that are “visible” to the immune system.

Enter mRNA vaccines. You create a synthetic mRNA to code for the specific part of the spike protein that is visible – just that small part – and get that mRNA into the cell and have it translated. Synthetic mRNA is the easy part, readily doable in any modern lab. Then, just like the viral mRNA, the cell translates the synthetic mRNA into protein, presents it to the immune system, which in turn creates specific antibodies against it. This is what it means to “train” the immune system. With that, you’ve now got circulating antibodies that will bind to any peptide that looks like that, including the “visible” peptide on the spike protein of the virus! Bind they do, and now the virus is prevented from getting into your cells. Game over, immunity achieved. Detail

The point is the “active ingredient” of both the virus and the vaccine is mRNA. Both leverage the normal molecular machinery of the cell to do all the hard work for free! This is a very different approach compared to how previous vaccines were developed. The most difficult part of getting this approach to work is getting the vaccine mRNA into the cell, which evidently Pfizer and Moderna scientists have figured out. mRNAs are also easily degraded which is why the vaccines need to be kept so cold during distribution.