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HW performs some needed trail maintenance. This was very near the White Line “trail” looming above the Chicken Point overlook in Sedona, AZ. You can see portions of it behind HW, a thin white streak set against the ferruginous sandstone. I put trail in quotes because to observe the White Line from the overlook below you’d think a person would have to be daft to try and traverse it on foot, never mind on a mountain bike. One slip up is all it would take to fall to the canyon floor below, some 150-200′ (?) Yet certain intrepid souls attempt it all the time

Completing the challenge requires cycling along the line right to left, and then at one point descending while turning 180º to ride a lower shelf back to the starting point. Seriously, take a look at that verticality! This is the most terrifying point in the traverse, because as you descend that 25′ or so you’re pointed directly downhill, right into the jaws of the canyon 😲 Like that first guy up there. The rider behind him stopped at that point, evidently deciding he’d prefer to live to ride another day, and butt-slid down it while holding his bike in front of him. On reaching the shelf below he carefully re-mounted his bike and pedaled back to the start. Even that part would be terrifying to ride if you ask me.

Yes, one could very easily die attempting this feat. According to locals nobody has, although some have fallen off their bikes but managed (somehow) to grab hold of the rock and “stick” to it to prevent falling to their death. Their bikes weren’t so lucky. The canyon floor, I assume, is littered with bike debris.

Unable to resist a closer look my friend Scott and I hiked up to the start of the line. The rest of our group followed a bit later. This is Scott with his hand on the start of the White Line. Gives you a real sense of the steepness and exposure of this beast

For sure we have ventured out on mountain bikes ourselves, to explore the red rocks and their various declivities. Although we limited our rides to the blue trails (intermediate) avoiding black diamonds altogether. As they say – Live to ride another day!

We’re here for about five weeks, chilling at a VRBO, with numerous friends visiting throughout.

By night, other visitors parade through the front yard. Black Dog’s never seen anything like em 🤨

We’re on the road. We shipped one of our cars to Washington state, I’m here with it now awaiting the arrival of HW and Black Dog. The car arrived days ahead of schedule and sat in a warehouse until yesterday. The battery was dead and even after a jump none of the features on the key fob worked (door lock, auto-start, open/close rear hatch). Drove to NAPA for a battery test, it passed, but barely. Stopped and restarted the car but the key fob features were still non-operational. So I drove to a nearby dealership for a new battery and key fob reset. Amazingly, service was open and not too busy, they got me in straight away, in about an hour I was good to go.

Shout out to Sharps Roasthouse. 1/2 rack of fruit-wood smoked St Louis ribs, mashers, coleslaw, rings of grilled corn. Played well with a glass of Washington State Pinot Noir. First restaurant I’ve been to that required proof of vaccination or a recent negative test to get in. Fortunately, I’d brought my vax card along.

Ukraine…smh. Can we get some adults in the foreign policy room, plz.

Headed further south this afternoon!

Afternoon Cortado with a flourish

HW, Black Dog, and Winter. We’re here four or five days a week. Not uncommon to have it all to ourselves. Only now and then do we pass by skiers, fat-tire bikers, or other dogs and their uprights. Soon we will leave this for a many weeks adventure to warmer climes, though surely none as tranquil as this. By the time we return the bears will be stirring and geese arriving. Steady as she goes.

The Optimist’s take on a birthday: A day younger than tomorrow. That assumes my tomorrow will come, the uncertainty of which gives credence to the Philosopher’s take: Live for the day.

Today I’m in search of a word that means the mixed feeling of relief and surprise one has on realizing an outcome or goal. At 62 my thoughts drift back to that early winter night, a young me in the passenger seat of a chopped Nova tricked out with ultra-wide racing slicks, the invisible black ice on the overpass, that feeling of the back end letting loose, fish-tailing wildly – left, right, then left again – before magically correcting and then we were off the overpass back on the frontage road like nothing had happened. Even as I turned to look at the driver, my friend, to see if he felt like I did, that what had just happened back there could have gone very badly for us, knowing full well there was no way that silly little guard rail was gonna stop no two-ton Nova douhnuting out of control from flying off the overpass and smashing on the road below. When finally he turned to look at me his eyes were like two full moons – I could have been looking in a mirror. One of those rare times between friends when no words need be spoken, he knew what I knew.

These are the close calls that give parents gray hairs to hear retold. And I’ve had others over the years, hasn’t everyone? Certain times when the laws of probability might have broken left instead of right. And some close calls we’re not even aware of. I sometimes remark in mixed company when the discussion turns to lucky breaks and getting old that we’re all one cell division away from our next birthday not arriving. Replicating 23 pairs of chromosomes every time a cell divides need go wrong just once to get the big-C going. But DNA replication mistakes aren’t something you experience happening. Multiple sclerosis afflicts many people, although the typical decades of onset for this disease are your 20s or 30s. Not that you’re out of woods in your 40s, but that’s roughly when the law of probability starts to bend in your favor, when you’ve dodged another bullet. The list of close calls goes on.

Still, it remains true that the strongest correlate for no more birthdays is age. There is no better predictor. So live for the day and don’t skip on the treats. I famously like to remind people (as HW would tell you 🙄 ) – “Don’t forget, half the people on the Titanic turned down the dessert tray!”

It’s a sad story what happened to Ms. Holmes. Sad in the sense that I wish the fraudulent claims about Theranos’ technology had in fact been true. What I don’t understand are Ms. Holmes’ true motives. Did she want to transform the way blood tests were performed and analyzed, to improve accuracy, reduce the cost, save lives? Did she only want to get rich? Did she overfeed on vanity and praise bestowed on her by those in her entrepreneurial orbit, some who thought she may be the next Steve Jobs? (The black turtle neck and hypnotic stare make the comparison hard to avoid). In other words, was she merely a victim of a runaway ego? When you lure otherwise very smart people to invest tens of millions of dollars in what you know is fairy dust, maybe you eventually come to believe it too.

A short review of Ms. Holmes ascent to tech stardom. In 2002, at age eighteen, she attended Standford University, nominally to study the Mandarin language, but she also dabbled in chemical engineering only to drop out in 2004 to open a healthcare technology company, which she later renamed Theranos (a portmanteau of Therapy and Diagnose). OK, so, fluent in a foreign language – check. Has the academic chops to study chemical engineering at Standford (where I assume she did well) – check. Has a good pedigree, i.e. smart parents and entrepreneurial ancestors – check. Has gained the confidence of a full professor of chemical engineering (also Standford) that her invention is going to transform healthcare forever – check. In short order she becomes the darling of venture capitalists – check. Who, by 2010, had invested $92 million in Theranos, where Ms. Holmes was the CEO – check, check. Not too shabby for eight years of effort!

By 2014, Theranos was valued at over $9 billion, way more than enough to join the Unicorn Club. Even less shabby for twelve years of work!

And then the bubble sprung a leak. The transformative technology Ms. Holmes duped investors into believing Thernanos had (and, to be fair, others were in on the dupe – her ex-boyfriend and co-worker has also been indicted for fraud) was all smoke ‘n mirrors. A special pin inside a tiny plastic capsule (the “nanoliter”) would draw a single drop of blood from a patient’s finger that would then be swiftly analyzed by Theranos’ proprietary software called “Edison.” Supposedly, Edison could detect and measure the levels of all kinds of bio-molecules (sugars, proteins, enzyme products, etc.), maybe even cancer biomarkers! This last being the holy grail of any number of biotech startups. Think “Cologuard” here. Maybe you want to know if you have colorectal cancer. Sure. But why push a camera up your butt and take biopsies when you can simply poop in a cup instead. Better yet, instead of poop, Theranos only needed a nanoliter of your blood. And then, Ms. Holmes said with the voice of a sage, software would do the rest.

Well, turns out, the most of the patients subject to the Theranos “tech” did not, in fact, have their blood drawn by the nanoliter, it was was drawn with a conventional syringe. And then most of samples had to be diluted to increase volume so as to be useful for analysis on a conventional blood analyzer, not Edison. The small percentage of samples that were analyzed by Edison gave irregular values and showed serious problems with reproducibility. The so-called transformative technology Ms. Holmes had been describing to investors for years (and patients as well) was fiction.

I agree with one reporter who was disappointed the jury did not find Ms. Holmes guilty of defrauding patients, only the investors. More than a few patients named in the lawsuit were told they had a medical condition based on a Theranos test when in fact they didn’t. Sure, even conventional, well-vetted medical tests can be wrong (false & negative positives), and patients have the right to be angry and sue, but being told the underlying technology of your test is as good as the current standard, or better, when in fact it was BS seems to me a quantum leap in criminal misconduct. But then again I’m pretty cynical toward the law in general, plus I wasn’t privy to the facts of this case as testified to in court. In any case, Ms. Holmes is likely facing many years behind bars for the three counts on which the jury found her guilty. Sentencing is scheduled for September.

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Not so long ago I was a vice president at a biotech startup, albeit an embryonic one much smaller than Theranos. I presented our technology at conferences and to scientists at pharmaceutical companies (we also won an NIH grant). I tried to convince would-be customers (not VCs) to invest in our solution for discovering novel biomarkers of human disease. We did OK for a few years, financially speaking, especially given we were a small startup. Eventually we had to close up shop, for a variety of reasons. But it wasn’t because the company principals (myself included) were ignominiously dragged into court with our tails between our legs. I may never have achieved the status of “player” in biotech but I’m also not facing ten years (or more) in jail. Moral of the story: Tell the truth. Ms. Holmes would have done well to add that to her list of self-improvement notes on hotel stationary. Not trying to sound morally superior, just sayin’. Certain words of wisdom are eternal.

An amusing view of the year in the rear.

Happy New Year. 🤞

I feel much better, dare I say fully recovered. There is no trace of the horrible hives visible anywhere on my skin. My hands and forearms occasionally still itch, weird given there’s no evidence of a rash or reddish skin. Truly, I thank all of you who wrote or called to inquire how I was coming along, and to wish me well. Life at 61.2° north latitude can make one feel a bit isolated, especially now on the eve of the annual Endarkenment. Bless you all.

November 9th: This is Kincaid Bluff where I often walk with Black Dog. A place where owls and eagles sometimes come to hunt, and a great place to be alone with your thoughts. During the week there are very few people here. If you’re not careful, though, as one walks about the mind can get caught up in what seems like an infinite loop of self rumination. When that happens to me I know it’s because I’ve slacked off on my meditation practice.

Eleven days later in downtown Anchorage outside a restaurant where HW and I stopped for a drink. By then it had turned unseasonably cold, evidenced by a clear night sky, rising smoke and condensed water vapor. The west wind that night didn’t help either (note the three flags – American, British, & Alaskan).

Wait, the Union Jack? Yes, that’s the Captain Cook hotel. Some British based company still holds an ownership interest (iirc). There’s also a statue of Captain James Cook near the hotel, erected on the bluff overlooking Cook Inlet. Rather than revere him, certain folks want to cancel him. I’m of two minds about this. Actually, three. One, I’m not big on statues to begin with. It seems to me there are better ways to commemorate the life of an individual who has done good things for society other than erecting a massive metal likeness in the public space. Especially where controversy exists over whether the person is really good or not, like someone more deserving of an anonymous grave than a memorial (looking at you Saddam). Two, back to Captain Cook, he was unquestionably an intrepid explorer (cancelers would counter exploiter) sailing about the globe checking off a number of firsts for global navigation and the Royal Navy. He deserves a bit more than a hat tip for that if you ask me. But (thirdly), he wasn’t exactly Mother Theresa in every encounter with indigenous people, and I get that, but it seems to me too often cancelers cherry-pick their objections where they feel culturally aggressed. Heck, you can even find people who don’t believe Mother Theresa was the saint the Pope declared her to be.

Wine Turkey Friends, in case you’re wondering

And then Thanksgiving arrived. Our friends and hosts (left) had us out to their house on the lake, an hour drive north of Anchorage. We all imbibed generously and packed our pie holes with prime rib, smoked turkey, salads and sides galore. For desert, we plied our pie holes with pie. The hives would start three days later, not caused by anything to do with Thanksgiving, of course.

It’s become a custom of ours at Thanksgiving to go around the table and have each person offer one thing s/he is thankful for. When it came to me I said, sincerely, I was thankful for the Covid vaccines. If not for the vaccine then Thanksgiving with friends, and other gatherings throughout the year, may not have been possible out of an abundance of caution.

…

If that thing I was thankful for surprises you, if it seems inconsistent somehow with my worldview of things or political tribalism, then allow me to disabuse you of that misconception right here.

By now there is so much accumulated misinformation about the Covid vaccines, mostly the mRNA variety, that trying to correct an individual’s mistaken beliefs is like a game of Whac-A-Mol. “They’re unsafe, they’ve never been approved by the FDA!” or “Nobody really understands what’s in those shots, I ain’t puttin’ that shit in my body!” or “Don’t do it, it will alter your genome!” or “The shot is pointless – you can still get Covid!” or “It’s a conspiracy by the Democrats to control us, they want to take away our freedoms!” Or or or… you get the idea.

Let’s talk about the science. Actually, I already got started on that here, a summary of what I found to be an interesting feature of the mRNA technology around the time the vaccines were first approved by the government under an emergency use authorization (EUA). Does EUA mean the government bypassed the usual rigor of FDA clinical trials (Phases I-III) that ordinarily must be passed to finally approve a drug (vaccines included) for use in humans? Yes, technically speaking, that entire formal process was bypassed for the mRNA vaccines. However, what is emphatically not true is the nonsense that no testing was done in real humans before the EUA. Over 30,000 people were enrolled in a trial to assess the efficacy of the Moderna mRNA vaccine, and 40,000+ volunteers were enrolled in a separate trial for the Pfizer vaccine. Roughly half the people in each trial were given the vaccine, the other half placebo. They were followed for a time and the results published (Moderna, Pfizer) in a highly respected scientific journal. The efficacy in both trials was astoundingly good (>90%) at preventing Covid-19. Specifically, against the founder variant of SARS-CoV-2, but later both vaccines proved highly efficacious against the Delta variant as well. In the end, over 35,000 real adult humans received 2 doses of an mRNA vaccine and not a one of them grew a third eye or suffered any near term pathology. None of them died. Most of them, however, avoided getting infected by the virus and sick with Covid-19. Infections and illness in the placebo group were, of course, significantly higher.

For skeptics who might still complain this “experiment” was too small to merit rapid approval, I have to wonder, how on earth would they know? How can it be so many people, who before Covid couldn’t tell you a single fact about what ingredients are in a given drug, never mind how its safety and efficacy were assessed, suddenly become experts in assessing the results and experimental design related to the mRNA vaccines? This is especially suspicious in light of the long-standing harsh criticism of the FDA that, if anything, the drug approval process in this country has been – and continues to be – far too slow. Thus delaying (or preventing) potentially life-saving (-extending) therapies to Americans suffering from major illnesses. But now, suddenly, some of these same people are suspicious that a highly efficacious vaccine to prevent death by infection from a virus, was hurried? Sorry, that trips my BS detector. I would bet you that any person who advises against getting a vaccine shot merely because it is “experimental,” had this person failed standard treatment for his cancer and was offered an unapproved, experimental drug that might save his life or delay dying from it, would jump to volunteer for that trial! But a vaccine against a virus that’s killed hundreds of thousands, that by now has been safely injected into tens of millions of people’s arms – well, one can’t be too careful you know 🙄

I intend no disrespect by that. It’s just that for people who are ordinarily rational and clear-minded, to lapse into this kind of epistemic brain fog…I dunno, I just don’t understand it. The only explanation that makes any sense to me is they’ve been swindled by pseudo-scientific grifters on the Internet.

Another thing: mRNA. Prior to 2020, ask your average person what mRNA is and you’d be met with a blank stare. Or ask ’em how a chemical car battery works. “What?” Point is, your average person (me included) doesn’t understand even the basic principles of many of the technologies we benefit from. I’ve talked about this before. And, as I concluded in that piece, it’s no different for drugs, which are a kind of technology. Except when it comes to drug technology I personally do know more about how the technology works (including the mRNA vaccines) than the average person does. So it peeves me to no end when I hear people’s vaccine hesitancy is based on misinformation – nay, complete nonsense.

I recently gave a short presentation to co-workers on this very topic, and for the same reason, to reduce any vaccine hesitancy among them and/or their friends and family. This is from the last slide in my deck

Focus on the first step (left) – DNA –> RNA –> Protein. It shows how protein is made, naturally, in every cell in your body. Unless you’ve had a class in molecular or cellular biology you likely would not know that mRNA (messenger RiboNucleic Acid) has been known since the discovery of the DNA structure by Watson & Crick to be the intermediate molecule whose sequence specifies the precise kind of protein to make. Far from being a toxic or scary substance, mRNA is in fact 100% natural! Every single cell in your body is constantly making new mRNAs for the ribosome to translate into protein. If that didn’t work, you’d soon die, or worse, you’d never have been born.

Fact #2: The Sars-CoV-2 virus is itself an mRNA virus! When it infects your cell it spills its contents (mRNA + other stuff) and hijacks the ribosomes in the cell to translate its own proteins (including the so-called Spike protein). This is the way it makes more copies of itself, and eventually makes you sick. The genius of the mRNA vaccines is this: We’re fighting fire with fire – brilliant! This is because the active ingredient in the vaccine (mRNA!) codes for just the Spike protein. Once inside your cells the vaccine mRNA is translated into viral Spike proteins. Once those proteins are booted out of the cell they train your (adaptive) immune system to be recognized as foreign. So that if you subsequently get infected with the virus it will be targeted and destroyed by the immune system. The only other stuff in the vaccine formula is a little sugar and fat to stabilize the mRNA so it can get into your cells to develop immunity. That’s it, nothing super different, chemically speaking, than what you’d find in a Starbucks latte.

“But wait – I heard the mRNA can alter my genome!”

No, false. Generally speaking, neither the mRNA in the virus nor the vaccine can be converted back into DNA inside your cells. It’s possible to achieve experimentally, but suffice it to say it doesn’t happen in this context. Advanced topic that.

“But you had a nasty adverse reaction to the Moderna booster shot, didn’t that cause hesitancy in you?”

No. I’m evidently in a minority of people who experienced a bad reaction, an overstimulated immune response, I believe. As I’ve mentioned before on this blog, biology is hard, very hard, and drugs have side effects, which can be variable across individuals who take them. But the benefit of vaccination against Covid clearly outweighs the chance of an adverse reaction. The latter being something I can (and did) endure, the former may kill me. If your calculus is different, if you don’t think Covid will kill you, fine, don’t get vaccinated to protect yourself, do it for your family and friends and others in your social sphere, to reduce the chance of spreading it to them if you do get infected. Don’t not do it because the Democrats urge you to, or because Joe Biden wants you to, or CNN implores you to; do do it because it’s the rationally correct choice to prevent yourself and others from getting sick and possibly dying. Otherwise, self-isolate. Those are the only rational options as I see it.

Still hesitant? Consider the above photo: One of eight (!) aisles at our local Natural Pantry store packed with over-the-counter pills, potions and tinctures for whatever ails you. What do you wanna bet “The Cleaner” (foreground) is nearly sold out because some debunked, quackpot ophthalmologist in Oklahoma convinced tRump it works as well as a swig of household disinfectant to kill the virus. 🙄 Point is, lots of people exhibit no hesitancy to waste their money on this crap, the lot of which has zero credible evidence of efficacy in any pathology they intend to treat. Yet many of these same people are deeply wary of a vaccine proven, in real human beings, to prevent getting severely sick and dying from a virus. Go figure.

“They mostly come at night…mostly.”

-Newt (Alien the movie)

I suffered (and still am) a severe outbreak of hives. First time in my life. They erupted suddenly in the wee hours of the morning eleven days after receiving a booster of the Moderna vaccine. We ruled out allergens as a cause, such as food, exposure to weird animals, travel-related interactions, laundry soap & dryer sheets, etc. And I’ve never had an allergy to anything in my life. So nothing made sense as the cause except the booster. But eleven days delayed? I was dubious. Then I started reading around. Sure enough, I’m not alone.

Spent the better part of the last four days since the onset of symptoms researching disease pathways in Chronic Spontaneous Urticaria (aka Hives). The chronic form of hives refers to a condition lasting more than six weeks, less than that and it’s classified as acute. I’d like to think this crap will resolve before six weeks, but everything I’m reading where the vaccine was the likely cause indicates maybe not.

Thing is, my particular brand of this misery, since it was not caused by an allergic reaction to food or medicine or what have you, is classified as “etiology unknown”, doctor speak for we don’t know what the cause of your type of hives is, Rod. As I said, I’m quiet certain the cause was the vaccine but I don’t think it was an allergic reaction to anything in the vaccine formula (e.g. Polythelene Glycol (PEG)). If so I would have had this problem after the first or second shot earlier this year, and I didn’t. Rather, somehow the booster shot over-activated an immune response pathway in me (and apparently in roughly 1% of all vaccine getters), presenting similar to what is seen in an allergic response, but through a different biological pathway. If this turns out to be a chronic form of hives there’s not much information on how long beyond six weeks the hives might last and what treatments work best to deal with the symptoms. The worse symptom, as any hives sufferer will tell you, is the inability to fall asleep and stay asleep. This is because the hives come out at night and are intensely itchy. During the day the itchiness is way down, and scratching more easily resisted. Creams, ice, and antihistamines all help inhibit the itchiness and hive production but they don’t stop it entirely. Something about trying to fall asleep in a supine position in a warm bed makes it worse. Standing or sitting and focusing the attention makes the itchiness fade away I’ve found. Steroids (e.g. prednisone) suppress the immune system and they have helped tone mine down and curtail hive production, but hard to say how much.

This unfortunate experience hasn’t turned me into an anti-vaxxer, although to be completely honest, had I known this would happen I would not have gotten a booster. There are other ways to protect yourself from getting infected with the virus and getting sick with COVID, like staying home and going out only when necessary. Not ideal, but practically speaking HW and I are now able to do that.

And now if you don’t mind I’m off to try and get some sleep. Not optimistic.