Brigham Young: Don't Expect God to Save You From Your Own Folly

In July of 1868, the Saints in Utah were struggling with grasshoppers destroying their crops. Twenty years prior had been the miracle of the seagulls, but it wasn't a permanent solution. Brigham Young spoke and noted that the Saints had been counseled for years to store up grain and hay, but had instead sold it to ouside markets for cheap. Below are some extracts from his lengthy speech [1].

I believe the Latter-day Saints are the best people on the earth of whom we have any knowledge. Still, I believe that we are, in many things, very negligent, slothful and slow to obey the words of the Lord. Many seem to act upon the faith that God will sustain us instead of our trying to sustain ourselves...

Some try to exercise faith and ask the Lord to remove this destructive power. I remember saying in the School of the Prophets, that I would rather the people would exercise a little more sense and save means to provide for themselves, instead of squandering it away and asking the Lord to feed them...

But some may say, "I have faith the Lord will turn them away." What ground have we to hope this? Have I any good reason to say to my Father in heaven, "Fight my battles," when He has given me the sword to wield, the arm and the brain that I can fight for myself? Can I ask Him to fight my battles and sit quietly down waiting for Him to do so? I cannot. I can pray the people to hearken to wisdom, to listen to counsel; but to ask God to do for me that which I can do for myself is preposterous to my mind...

[The people] are in want and in trouble, and they are perplexed. They do not know what to do. They have been told what to do, but they did not hearken to this counsel...

Let crickets, or grasshoppers, or frosts, or anything else come and destroy our crops, and we feel it then; but just as soon as prosperity comes we forget what has happened...

Take the people and I am proud of them; but there is a feeling with them that they must not be counseled in their temporal matters. I call this a sectarian notion, for we will find yet that God is Dictator in everything...

How much credit was due to [the children of Israel led out of Egypt]? Just as much as to us, for not saving our grain when we had an abundance, and, when the grasshoppers come, crying, "Lord turn them away and save us." It is just as consistent as for a man on board a steamboat on the wide ocean to say, I will show you what faith I have, and then to jump overboard, crying, "Lord save me!" It may not seem so daring; but is it any more inconsistent than to throw away and waste the substance the Lord has given us, and when we come to want, crying to Him for what we have wasted and squandered? The Lord has been blessing us all the time, and He asks us why we have not been blessing ourselves...

Who are deserving of praise? The persons who take care of themselves, or the ones who always trust in the great mercies of the Lord to take care of them? It is just as consistent to expect that the Lord [will] supply us with fruit when we do not plant the trees; or that, when we do not plow and sow and are saved the labor of harvesting, we should cry to the Lord to save us from want, as to ask Him to save us from the consequences of our own folly, disobedience and waste [2].

Notes:
1. Journal of Discourses, Vol 12, pp 238-245
2. This paragraph was quoted in the manual, Teachings of Presidents of the Church: Brigham Young

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Initial Thoughts on Omicron and Vaccines

You've no doubt seen discussion in the news and social media about the emerging coronavirus variant called Omicron. It was first detected in South Africa, but is now in many countries including the U.S. Because it is fairly new, it's hard to say much definitive about it. I recommend keeping an eye on knowledgable commentators (a few links below).

Initial data from South Africa suggest that it is spreading very fast, and that prior infection with COVID does not give protection (at least robust protection) against Omicron. How well the vaccines protect remains to be seen, but we will likely see a lot more breakthrough cases than with Delta. The reason, simply put, is that the Omicron spike protein has changes that will prevent some of the antibodies that were previously generated from recognizing the Omicron spike. It's not all or nothing; rather, it's degradation by degree.

I made the following figure to illustrate how I think about COVID vaccines. Ideally, most people stay in the first stage, and very few people proceed to the bottom stages. With Omicron, we will probably see more people (either vaccinated or previously infected) go further down than they would if this was just another Delta wave. People with no COVID or vaccination history are simply at the mercy of nature.

What can you do? The same kinds of things you've already been doing. However, you need to be fully vaccinated, including the booster. For one thing, the Delta variant is still very prevelant and we are heading into winter [1]. So you want to be as protected as possible against it. But even if the vaccine isn't as potent against Omicron, there is every reason to expect that it will still be helpful. Whether you have previously had COIVD or not, get fully vaccinated so that your immune system is as prepared as possible for Omicron. Even if the antibodies are not as good as they could be, having them at higher concentration will help. Also, there's more to the immune system than antibodies (namely, T cells), and they need to be on high alert too.

A Few Suggested Information Sources [2]:
Your Local Epidemiologist (Katelyn Jetelina) (Twitter / Substack)
Scott Gottlieb (former FDA commissioner)
Carl Zimmer (science reporter - one of the best in the business)

Notes:
1. As our family was leaving for our Thanksgiving trip, we learned of deaths in the extended family of some friends. The friends were vaccinated, but their rural relatives refused to get vaccinated (for the reasons you can imagine), even though an uncle had died of COVID. A birthday party for the father became a superspreader event, resulting in four hospitalizations. The father died, and at the last update a 31 year-old cousin was on a ventilator and expected to die [update: confirmed dead]. You make your choices, but you don't choose the consequences.
2. I've chosen a few relatively non-technical resources. Keep your eyes on these professionals and those they recommend. Beware of contrarians.

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Sure, Go Ahead and Undo Your Vaccine

I have to admit that I got a bit of a chuckle from an NBC News article about people giving in and getting vaccinated, and then "undoing" it.

In a TikTok video that has garnered hundreds of thousands of views, Dr. Carrie Madej outlined the ingredients for a bath she said will “detox the vaxx” for people who have given into Covid-19 vaccine mandates.

The ingredients in the bath are mostly not harmful, although the supposed benefits attached to them are entirely fictional. Baking soda and epsom salts, she falsely claims, will provide a “radiation detox” to remove radiation Madej falsely believes is activated by the vaccine. Bentonite clay will add a “major pull of poison,” she says, based on a mistaken idea in anti-vaccine communities that toxins can be removed from the body with certain therapies.

Look, unless you are under the care of a physician--probably at the emergency room, it's a virtual guarantee that anything that claims to 'detox' you is utter baloney. In fact, I'll go so far as to say that the word 'detox' is a bright red signal that you are probably dealing with a charlatan.

That's why I thought the article was funny. People who are into 'detoxing' themselves have already left the realm of medical/scientific reality. Why would they care about a news article that tells them that they can't undo or "detox the vaxx"? Excuse me, TikTok says otherwise.

But, since getting a high proportion of the population vaccinated is a good thing, there's a part of me that wants to go along with this. Here's what I might say:

Oh, no! Don't you dare get the vaccine and then take a bath and smear mud on your skin! You'll ruin everything, and the government can't do anything about it! Now you know why doctors are so mad and don't want you to know about this one wierd trick!

That kind of marketing has to be good for something.

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Anti-Vaccine Sentiment is Not Uncommon Among Chiropractors

Following my last post on anti-vaccine lies told by a chiropractor, I came across two news articles (one new, the other from last May) that highlight that chiropractors seem to be a concentrated source of vaccine mis-information, something that existed before COVID but that has become more prominent in the wake of COVID.

AP News: Anti-vaccine chiropractors rising force of misinformation
The Atlanta Journal-Constitution: Some Ga. chiropractors are stoking fears of COVID vaccines

Both articles state that anti-vaccine sentiment comes from a minority of chiropractors, but they seem to have outsized influence. How much of a minority? It's hard to say, but the AP News article offers this:

AP could find no national numbers of vaccination rates among chiropractors, but Oregon tracks vaccine uptake among all licensed health providers, and the numbers show chiropractors and their assistants are by far the least likely to be vaccinated -- and far less than the general public.

Just 58% of licensed chiropractors and 55% of chiropractic assistants in Oregon were vaccinated as of Sept. 5. That’s compared to 96% of dentists, 92% of MDs, 83% of registered nurses, 68% of naturopathic physicians, and 75% of the general public.

Of course, mainstream medicine has its share of quacks and hucksters, and although I have never sought treatment from a chiropractor, I am willing to believe that most of them provide useful medical services [1] in the vein of physical therapy. The problem is that pseudoscience is baked into the history, philosophy, and sometimes the training of chiropractic. The AJC article is particularly interesting here because the largest chiropractic school, Life University, is in Georgia and it is still rooted in outdated 19th century medical ideas.

Such beliefs trace back to the founder of chiropractic, D.D. Palmer, who postulated in the late 19th century that most diseases and maladies are caused by spinal or joint misalignments, and therefore chiropractic adjustments can boost immunity.

Life University still embraces this concept of “vertebral subluxation,” though there is no scientific basis for it. During the height of the pandemic, the school’s guidance for faculty and students on how to prevent getting coronavirus included, “Get your spine checked and adjusted regularly to ensure your nerve system is able to optimally adapt to these external stressors.”

This is such unadulterated horse crap. The notion that an adjusted spine could protect you from contracting COVID is just as stupid as if I were to tell you that the COVID vaccine can protect you from getting a herniated disc. The problem here is that if your beliefs about health are wrapped around notions of mystical energies and "natural healing," then your diagnoses and treatments are going to be primarily concerned with unlocking said mystical energies [2] and promoting "natural healing". But healthy living, good nutrition, and great posture can only take you so far [3].

And yet, graduates of Life University who absorb these views are seen as doctors (with accompanying authority) in the eyes of the public, which is reinforced by their licensure by the state. This in spite of the fact that they are not licensed to prescribe drugs or perform surgeries. In Georgia, they aren't allowed to puncture the skin, so they presumably couldn't offer vaccination even if they wanted to.

Look, I'm not trying to demean any chiropractors out there in my readership, or their friends and loved ones. If they provide genuinely useful treatments to people and stick to their sphere of training and licensure, then God bless them. But the public should know that a chiropractor's sphere of medical authority is rather narrow, and the opinions of chiropractors on vaccines should hold commensurate weight.

Notes:
1. Some patients may also find social/psychological benefit from their visits.
2. An old chiropractor I knew once said that he had to understand quantum mechanics for his job. I was too dumbfounded and incredulous to ask questions.
3. As an extreme example, rabies virus travels up the peripheral nerves to the central nervous system. Once there, it is virtually always fatal in humans. No vitamin juice to aid "natural healing" or spinal adjustment to optimize nerve adaptation to such an "external stressor" has changed that. Vaccination or passive antibody treatment after a bite is your only real hope.

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A Chiropractor Tells Blatant Lies that Feed COVID Craziness

Apparently there is a movement on Facebook by anti-vaccine groups to discourage sick people from going to the hospital. Via NBC News:

Anti-vaccine Facebook groups have a new message for their community members: Don’t go to the emergency room, and get your loved ones out of intensive care units.

Consumed by conspiracy theories claiming that doctors are preventing unvaccinated patients from receiving miracle cures or are even killing them on purpose, some people in anti-vaccine and pro-ivermectin Facebook groups are telling those with Covid-19 to stay away from hospitals and instead try increasingly dangerous at-home treatments, according to posts seen by NBC News over the past few weeks.

Where does this kind of craziness come from? I'll show you an example. I recently came across a video of a chiropractor named Bryan Ardis giving a presentation at a right-wing event. He was spinning some yarn about how the death toll of COVID in the U.S. is a result of the drug remdesivir (among the treatments given to President Trump), which Anthony Fauci knew to be fatal, and how this is part of a murderous plot Fauci and the government have been carrying out. He compared the use of remdesivir to--and I am not making this up--the gas chambers of Nazi Germany.

This is all crazy enough [1], but the evidence he presented was what caught my interest. He referenced a study published in the prestigious New England Journal of Medicine from 2019 where remdesivir was one of four treatments tested against Ebola virus. Ardis emphasized that HE actually read the study, and alleged that remdesivir was pulled early because it killed 54% of the people who received it. This, he said, is why Dr. Fauci pushed using the drug for COVID--so that it would kill lots of people.

To prove that he wasn't lying, Ardis showed Table 2 from the Ebola study, drawing attention to the number I have highlighted.

Sure enough, 53.1% of the remdesivir recipients died. And it is true that both the remdesivir and ZMapp (triple monoclonal antibody) treatent groups were stopped early because more people were dying. There's just one problem: THESE PEOPLE HAD EBOLA!

In case you live in a cave and haven't heard of the Ebola virus, it's only one of the most deadly viruses on earth. The virus, not the drugs, was killing people. The remdesivir and Zmapp treatments were halted because the other two treatments were saving more lives, so it would be unethical to continue using inferior treatment [2].

Ardis's spin is such an egregious distortion of the study that we should be excused from bothering with his other claims, most of which are equally bonkers. He has clearly marked himself as an idiot, a lunatic, or liar. I mean, for heaven's sake, the table even breaks the death rate down between high vs low viral load, so that should be a big clue as to what's going on. He made the same claim on a podcast I found while checking into his background, so this isn't an isolated incident.

Ardis went on to show an internal Powerpoint slide from the FDA, drafted prior to the vaccine rollout, that listed a variety of possible adverse events to be monitored. According to him, the slide is proof that the FDA knew that the vaccine would cause such adverse events. This is so obviously stupid, but people eat this stuff up. He also made a plea for people to avoid ICUs and keep their loved ones out of hospitals because they will be subjected to this genocide. Instead, you should go to his website and get HIS recommendations.

It's worth noting, again, that Ardis is (or was [3]) a chiropractor, which means that he is not licensed to prescribe ANY drugs. And heaven knows that there is a lot of quackery that operates under the banner of chiropractic [4]. So by all means, let's take this guy's advice on medical issues he has no training in.

But if you do want to get his recommendations, you have to give him your email address. Why? Probably so that he can market his line of health products to you. In other words, in my opinion he is a health huckster seeking to create customers and build his public brand, and his value proposition is that he can save you from the tyranny of government-medical industry conspiracies. But first he needs to convince you that there is such a conspiracy [5]. But whatever the case, he is clearly not someone with any relevant training. And even if he did have relevant training, his claims would still be wrong.

At the risk of spreading misinformation, I am recommending that you watch his video here. You need to see how confidently and charasmaticly this guy speaks. Then look at who is promoting him and the other things they promote. Perhaps it will help you to develop your own BS detector.

Notes:
1. But sadly becoming routine enough that we hardly notice any more. Ironically, Ardis is only one step away from agreeing with China's baseless accusation that it was the U.S. that leaked the virus into the world.
2. Similarly, from a purely scientific point of view it would be preferable to have a placebo control group to compare to. However, Ebola is so deadly that it wouldn't be ethical to do that. Instead, there is an evolvoing 'king of the mountain' of treatments. A prior study suggested that ZMapp was superior to the prior standard of care, so in this study the ZMapp treatment was considered the benchmark for measuring the others against.
3. During my drafting of this post, I found this fact-check by AP News, which refers to Ardis as "a former chiropractor."
4. I tried to be careful with my wording because I don't mean to imply that all chiropractors are quacks, but the profession sure seems to tolerate a lot of them.
5. Isn't it funny that, if Ardis is to be believed, the government so casually publishes the evidence that it is trying to kill or damage you?

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Example of a COVID Chart Crime

A chart crime is when a chart is used in a misleading way [1]. It could be that the data are manipulated, cherry-picked, or the chart is simply designed such that true data lacks correct context.

Recently the cynical side of me was imagining how I could use COVID data to commit a chart crime. Here is what I came up with.

This chart showing U.S. COVID deaths per capita is extremely misleading, but I haven't monkeyed with the data at all. Can you tell why it is misleading?

Think about it this way: who are the people dying in this chart--especially in the peak on the right? Are they vaccinated or unvaccinated? If you are reading the news at all, you know the answer is that the vast majority of people dying of COVID have not been vaccinated. In fact, according to CDC data, as of Sep 13 there have been 3,040 total fatal breakthrough cases (i.e. vaccinated people who nevertheless died of COVID). By comparison, just since Aug 1 there have been about 60K COVID deaths (U.S. data only). So the mere fact that there is a spike in COVID deaths occuring in the face of the vaccine rollout means nothing for whether vaccines are efficacious or who is at risk of dying. You need more granular data to draw those conclusions.

Assuming the data are good, population-level data are useful for making comparisons between populations, and for developing hypotheses for further investigation. But you need to be careful about what conclusions you draw about particulars from population data alone because even if it is accurate, it masks complications in sub-groups going on underneath.

A word to the wise.

Notes:
1. The term was coined in the finance industry, where apparently chart crimes are common.

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COVID Vaccines: Letter to a Friend

An old friend recently contacted me with some questions about the COVID vaccines. I spent enough time composing my response that I thought I would post it here in case anyone finds it useful. Below is a lightly edited copy of my emailed reply.

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These are good questions. Instead of taking them point by point, I think it makes sense to address them in the course of a longer discussion. (Probably too long, but I can’t help it.) First, I should state that I am only giving general information and not specific medical advice. Ultimately, I would follow whatever your kids' doctors advise.

Messenger RNA (mRNA) is an intermediary between the genome and the cellular machinery that makes proteins. It essentially tells cells which amino acids to link together in order to make a protein. All proteins in the body (specifically in cells) are made using mRNA. When a virus infects a cell, it starts making its own viral mRNAs, which causes the cell to start making viral proteins. The spike protein is one of a number of proteins that the coronavirus makes. The spike protein is important because it is responsible for attachment to cells, and then entry into the cells. From an immunology and vaccine perspective, it is the most important protein because if you can make antibodies that bind to it in the right spot, the spike protein is unable to attach to or enter new cells. Thus, the virus is neutralized.

Right now there are two basic classes of approved coronavirus vaccines.

1. Moderna and Pfizer use mRNA technology. They take chemically synthesized mRNA (coding for spike) and formulate it with some lipids and cholesterol to form a nanoparticle that can be taken up by cells. mRNA is easily degraded, which is why it can't be simply injected by itself. It needs that lipid nanoparticle to protect it until it is delivered into cells. Cells have various mechanisms of sensing RNA that is out of place, so to speak, so the vaccine mRNA has slight chemical modifications to help avoid alerting cells to its presence. This is done in order to help maximize the amount of protein produced; otherwise the cell would try to shut down protein production, which would negatively impact the ability to generate a good immune response. Currently, two doses are considered fully vaccinated.

2. Johnson & Johnson and AstraZeneca (Europe) take a different approach. They use a different kind of virus called adenovirus as a delivery vehicle (a 'vector'). (They actually use different adenoviruses, but the principles are the same.) The adenovirus is modified in two basic ways. First, it is missing some key parts of its genome such that it can only replicate in special laboratory cells, but not in people. Second, the gene for the coronavirus spike protein has been added into its genome. When the adenovirus is injected, it can "infect" cells, but it can't make copies of itself. However, it does make spike mRNAs, which are then turned into the spike protein by the cell. Currently one dose is considered fully vaccinated.

Aside from a small mutation in the spike protein that helps keep it in the optimal shape for an immune response, there is no difference between the spike protein made by the vaccine vs spike made by the virus. The production of spike by both vaccines is transient. Ultimately, the mRNA and/or adenovirus are degraded, as is the spike protein that was produced. How long does the spike protein stick around? One study of some people who got the Moderna vaccine detected spike in blood for about 7-10 days after the first vaccination, and then barely at all after the second vaccination--presumably because the immune system was poised to deal with it quickly. I don't know whether comparable data has been generated for the adenovirus vaccines, but it would probably be something similar (but only one dose). There could be some trace amounts retained in lymph nodes for longer, which is normal and allows further honing of antibodies, but for all practical purposes I think it's safe to say that vaccine-produced spike is gone by 2-3 weeks. There is nothing about the vaccines that would make spike a permanent part of your body any more than natural infection would.

Any new vaccine or drug is tested in animals (if possible) and then gradually introduced into humans. First, 10s of people are tested for safety. Then a few hundred or thousand are tested for efficacy. Any obvious problems should be apparent at this point. However, in a genetically and biologically diverse population, it is impossible to predict whether more rare problems will arise. This is further complicated by the fact that weird and unexpected medical events happen every day. Sorting out coincidences from causal connections is a challenge, and the more rare the adverse event, the larger the population is needed in order to reach statistical certainty. Even when there is statistical certainty, the adverse events need to be weighed against the benefits.

I'm not intimately familiar with the FDA licensing process, but several factors came together that enabled the quick development of the COVID vaccines. First, the delivery systems (mRNA or adenovirus) already had a lot of research behind them. Second, previous coronavirus research made the choice of targeting the spike protein a natural one. Third, the expanding pandemic made it easier to generate the needed data to compare vaccinated vs non-vaccinated. It takes a lot longer to do this when a disease is less common. Finally, the federal government took on a lot of the financial risk. Ordinarily vaccine companies would wait until near the end of the process to invest in manufacturing facilities. In this case, the federal government essentially said, "Go ahead and start preparing for manufacturing while collecting the data from the early phases of evaluation. If it turns out that the vaccine fails safety or efficacy standards, we will cover the cost of having prematurely invested in manufacturing."

There are a few garden-variety side effects that often occur with vaccines. Things like fevers, aches, and so forth--basic flu-like symptoms that are really just automatic parts of an immune response. Other side effects become apparent over time and with larger populations. The CDC and FDA monitor these other side effects and provide updates on the most important ones here: LINK

As you noted, the adenovirus-based vaccines (J&J in the U.S.; Astrazeneca in Europe) have been associated with a rare clotting issue, resulting in a pause in their use earlier this year in both Europe and the U.S. I think the exact mechanism behind this isn't known for sure, but it doesn't seem to be as simple as the presence of the spike protein because the same thing has not been seen with the mRNA vaccines. Clotting issues of this type need to be treated differently than other clotting issues. Part of the reason for the pause was so that the word could get out to physicians that they needed to be aware of this association so that they did not inadvertently use the wrong treatment. The J&J vaccine has also been associated with a rare nerve issue.

The mRNA vaccines (Pfizer and Moderna), on the other hand, have been associated with rare cases of myocarditis, especially in young men after the second dose. The majority of these rare cases have resolved with minimal treatment. It is also worth noting that COVID infection itself can also cause myocarditis.

The duration and effectiveness of natural immunity vs vaccine immunity is still a developing story. It does appear that people with natural immunity have good protection against re-infection. Some studies suggest that they are better protected against re-infection than vaccinated people, and there are good immunological reasons to think that would be the case. However, studies also indicate that natural immunity can be further improved with one dose of vaccine, including better ability to neutralize variants. So as a generalization, I would say that when it comes to re-infection, natural immunity + 1 dose of vaccine is superior to either natural immunity alone or fully vaccinated without prior infection. (For people who have been previously infected, the second dose doesn't seem to add much additional benefit. On the other hand, keeping it at 2 doses (mRNA only) helps to ensure that all people are fully vaccinated.) To be clear, that doesn't mean that natural immunity is preferred, since that implies getting infected and likely having disease, something we want to avoid. It is impossible to predict what future variants may come our way. However, it looks increasingly likely that they will be sub-variants of the current delta variant. Presumably, future booster shots will incorporate updated variant spikes.

But let's come back to natural immunity for a moment. Like most things biological, there is a spectrum. Some people develop fantastic immunity, and others develop mediocre immunity, which is borne out by documented cases of re-infection. Although antibodies are only one part of the immune response, studies suggest that antibody levels correlate pretty well with protection. As far as I know, current commerically available antibody tests cannot be interpreted to indicate the level of antibodies or level of protection. They only indicate that antibodies are present. (The FDA warned about this in May.) If I had to guess where someone who never had symptoms falls on the spectrum of natural immunity, my guess would be on the weak, less durable side. My reasoning is that if the virus didn't cause symptoms, then it probably didn't replicate enough to really get the attention of the immune system. (The scientific literature is a little bit conflicted on this point, but some studies support my view.) Unfortunately, absent a more robust test designed to assess the levels and/or neutralizing capacity of antibodies, there's no way to know where any individual stands. This is part of the reason why people who have recovered from COVID are still encouraged to be vaccinated.

I take your point about long-term safety. (Although I would note that the long-term consequences of COVID aren't known yet either.) We obviously can’t see into the future, but I think this framework might help. Virtually all of the adverse events—even the rare ones—that have been observed have occurred within days to a couple of weeks of vaccination. That is the time when vaccine components are present, spike is being made, and the immune system is most active. So let’s call these acute adverse events. As I explained earlier, the vaccine and spike protein are gone within 2-3 weeks. After that point, any adverse events would have to either be leftover consequences of the acute adverse events, or some aberrant immune activity—like maybe the vaccine provoked the immune system to start attacking some part of the body (autoimmunity). With the possible exception of rare cases of Guillain-Barré Syndrome, I’m not aware of any such thing having been observed. There’s a sense in which anything is possible in nature, but it is hard for me to imagine how there could be any long-term adverse events—not connected to the acute events--that would spontaneously arise months/years after vaccination. Moreover, inasmuch as virus infection and vaccination both stimulate an immune response against the spike protein, it is hard for me to imagine how such a long-term adverse event could be specific to vaccination. That’s not a guarantee of long-term safety, but I think we should have every expectation of long-term safety for the vast majority of vaccinates.

I think I have taxed your patience enough for now. I hope this helps. I am happy to answer any follow-up questions, provide references, or explore other sources of information as you may desire.

Jared

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Why Anti-Viral Drugs are Hard to Come By

This post isn't specifically about hydroxychloroquine or ivermectin, but the craziness over using them as a treatment for COVID made me think that it might be worth a quick explanation as to why they, or any other known drug, are inherently unlikely to be anti-viral therapies.

Let's start with antibiotics--the medicine that you use to fight a bacterial infection. How do they work? Put simply, they work by screwing up the molecular processes of bacteria. They are small molecules that bind to or alter important bacterial enzymes. It's like throwing a wrench (spanner, for the British) into a machine, or a broom stick into the front wheel of a bike. Except, here we are talking about specific interactions between molecules because they have just the right shape and chemical properties. Antibiotics screw up the chemical processes that bacteria need to live and grow. The reason that antibiotics don't also screw YOU up is because bacterial enzymes are different enough from ours that they can be selectively targeted. You don't have peptidoglycan in your cell membrane, for example, and the ribosomes in your cells are a little different than those in bacteria. Thus, scientists have been able to find small chemicals that, at the right concentration, can kill bacteria and not you [1].  The same applies to parasites. This general concept is called selective toxicity.

So how come there aren't more anti-viral medicines? Why is it that a doctor will diagnose you with a virus and then usually say there's not much you can do but manage the symptoms? The answer is that selective toxicity is much harder to achieve with viruses. That is because viruses mostly commandeer your cellular machinery for their own purpose. They do use some of their own enzymes, but there aren't that many targets to go after. This is further complicated by the fact that there are dozens of viruses that can infect people, each with different enzymes, and even if you could find a small drug molecule to screw up that enzyme, the virus has a decent chance of evolving resistance. Also, you usually don't know that you are infected with a virus until you develop symptoms, and by then an anti-viral probably isn't going to do much for you anyway (unless it is a chronic infection). Simply put, it is hard to screw up a virus without screwing up your own cells too. That's just the science side of it; the economics of drug development are a whole additional dimension to the issue. So for the most part it is up to the immune system to deal with viruses, hence the importance of vaccination.

So the idea that some random drug that is good for something else would also just happen to specifically inhibit some part of the SARS-CoV-2 replication cycle is just inherently unlikely. Not impossible, but really unlikely. And just because something works in cell culture does not mean it will work in you. Cell culture is a starting point, not proof of efficacy!

But maybe we don't need the drug to specifically target the virus. Maybe it can just perturb some cellular process enough that the virus has a hard time reproducing while the immune system ramps up to take care of it. That's a theortical possibility, but if the drug isn't screwing up your cellular processes enough to cause you some really unpleasant side effects, then it probably isn't doing much of anything to stop the virus either.

In summary, unless approved by regulatory authorities, you should be very skeptical of claims that an existing drug also happens to be an anti-viral. The same goes for any kind of dietary supplement or non-FDA approved therapy. Remember, it takes chemcial sharpshooting to kill a virus without killing you. If you take a drug that isn't approved as an anti-viral, you are probably shooting the wrong target.

Notes
1. The drug, of course, has no idea what it is supposed to target. It just follows the laws of physics and chemistry.

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Time to Clean Up Some Vaccine Information Pollution

There is a viral video going around of a pathologist claiming that the COVID vaccines are toxic. It is a compeling talk, but it is garbage...in a sort of glorious way. Time for cleanup.

First, who is this guy? Dr. Ryan Cole is apparently an independent pathologist in Idaho who has previously attracted the attention of FactCheck.org, and has affiliated with a group called America's Frontline Doctors, which is a group of doctors with...let's say a contrarian take on COVID and public health. The video is of a presentation he apparently gave on July 27 to his like-minded colleagues.

Cole's basic claim seems to be that the Spike protein of the virus is responsible for most of the pathology and disease manifestations of COVID. Therefore, we should not be pushing vaccines that use the Spike protein on people, and especially children, since we don't know what the long-term effects will be. (As if we do know the long term effects of COVID infection?) Also, we should be doing more autopsies of people who die after having had the vaccine in order to determine whether there is a causal connection.

I've stated his thesis using calmer and more neutral language than Cole, and put this way it seems like a reasonable position. When watching the video, I quickly determined that this was a guy with an axe to grind. There's nothing wrong with being passionate, but the way that he derided the vaccines made it clear that this wasn't just a doctor with some scientific concerns. It was almost like he was trying to come up with his best insult. At one point he said, "these are not vaccines," which is kind of a stupid thing to say because they are, in fact, vaccines. (Maybe he has his own special definition?)

Before I address his claims, I need to do a spoiler alert. Just like knowing how a magic trick is done or how a mystery ends can take away the feeling of wonder, what I am about to explain may deny you the opportunity to feel the same sense of fear and indignation toward the vaccines and medical establishment that you might otherwise feel. So if you want to feel the tension build and wonder how it could possibly be resolved, go watch now and do not read further.

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OK, I'm going to do the big reveal up front, but we'll still go through the journey. Here it is: NONE of the scary pictures of inflammation that Cole shows are from a vaccine. Even worse, some of them are actually from COVID patients. You may find that hard to believe, but stay with me.

Inflammation
If you haven't watched it, much of the talk consists of Cole showing slides of tissues and commenting on the inflammation. You could be excused for thinking that these were from cases that he investigated or experiments that he did. In fact, at the 4:45 mark he says, "We did studies in lab animals." He must have meant the royal 'we' because there's no evidence, that I can find, that he has been involved with any animal studies dealing with COVID. None of the image slides contain references, but thanks to the magic of Google I was able to track them all down. They are all pulled from the scientific/medical literature, or from medical news articles.

I'm going to go through each of them and comment on his claims. Because I am lazy, I don't feel like reproducing all of the images here, so I'll just give a description, where in the talk they can be found, and provide links to the image sources so you can check them out for yourself.

1. (5:20) Endothelial cell mitochondria (black, purple, and rainbow colors) - Claim: The damage is caused by Spike alone from the vaccine, not the virus. Fact: This is wrong. No vaccine was involved. What the researchers did is to make inert viral particles that have the Spike protein and treated endothelial cells (in the lab) with these particles. Yes, they attributed the observed, effects to Spike, but it is a logical leap to say that the vaccine would do the same thing--or be biologically meaningful if it did. In fact, the article suggests that a vaccine would be protective.

2. (6:57) Lung tissue (the image appears to come from news articles, like this one, that describe results that were later published) - Claim: disease is from the vaccine. Fact: Again, no vaccine was involved in the study. The researchers injected part of the Spike protein directly into the trachea of mice. Perhaps it shouldn't be surprising that putting a foreign protein directly into the airway caused inflammation. It's an interesting finding that helps inform us about the disease process, but it's another logical leap to say that the vaccines would cause the same effect. More about this later, but for now the practical takeaway is don't snort Spike powder.

3. (8:16) Brain cells - Claim: inflammation from Spike. Fact: This comes from the autopsy of a man who had the first Pfizer dose but caught COVID 3 weeks later while at the hospital for other health problems. His death was ruled not to be due to COVID infection, since they did not see typical signs of COIVD, but many of the tissues sampled (including brain) had viral RNA and he was well past the point when Spike would have been present from the vaccine. At any rate, it's no surprise that having virus in the brain would lead to inflammation.

4. (8:28) Heart images, myocarditis (scroll down) - Claim: "That's after a shot." Fact: These images are from a public database of radiology images. The case description does not mention COVID or the vaccine. It's true that there are some rare cases of myocarditis associated with mRNA vaccination (but not the Johnson and Johnson vaccine), and it could be that this image is representative of such cases (I'm not qualified to say), but this image is not from someone who had a vaccine. Cole probably pulled it from an online news article that used it as a stock image (like this one) and mistakenly thought it was actually from a vaccine patient.

5. (8:55) Heart tissue - This image does not have anything to do with COVID at all. The top pictures are from an entirely different virus, enterovirus A71.

6. (9:50) Kidney - The rest of the images are shown in rapid succession and can be addressed together since they can all be found in the same article. Fact: All of these images are from people who actually had COVID.
7. (10:05) Liver
8. (10:15) Testes

If you are wondering why Cole would show tissue slides of people who had the disease (or even a different disease) and then claim that this is what the vaccine does, you're asking a good question! I think the most charitable answer I can give is that Cole has taken the data from the mice with Spike injected in their airway and extrapolated to the conclusion that all COVID inflammation comes from Spike and therefore the vaccines (which cause your cells to make Spike protein) cause pathology equivalent to COVID disease. That's quite the extrapolation! And it's plainly false just from a clinical perspective. (Are vaccinated people having to monitor their oxygen levels?) So if you follow Cole's logic, you should avoid the vaccines and instead leave yourself open to becoming infected and getting the types of pathology that he has shown in his slides. (Joke: maybe it's best that Cole's patients are already dead.)

Miscellaneous
The images are really the main story, but there are a variety of other claims and issues that need to be addressed.

First, let's go back to the mice that had Spike protein (actually only part of the Spike protein, S1) injected in their airway. Consulting the paper, the scientists gave the mice 400 micrograms of Spike per kg of the mouse weight. Cole mentioned a Harvard study that measured the circulation of Spike in the blood of people given the Moderna mRNA vaccine. Spike (S1) was only detectable for 9 days or so after the first shot, and virtually not at all after the second shot (consistent with the rise of antibodies). At the peak of S1 circulation, the average amount was 68 picograms/mL. Let's do some math. The Internet tells me that an average adult human has about 5 liters of blood. Let's make it 6 L, which is equal to 6,000 mL. 6,000 mL x 68 pg/mL = 408,000 pg = 0.408 micrograms total. Let's assume a weight of 90 kg (~198 lbs). Divide 0.408 micrograms by 90 kg = 0.0045 micrograms/kg. Do I need to continue in order to make the point that the mouse study used WAY more S1 protein than was found in the blood of vaccinated people?

(7:43) Spike crosses blood brain barrier (BBB). The slide accompanying this claim contains the only references provided in the whole presentation. Note that the slide title, "Spike as Toxin" comes from Cole, not the referenced articles (here and here). Poking around the literature, the focus seems to be on the ability of the virus to invade the central nervous system. I am unable to find any literature that addresses the BBB in the context of vaccination. However, I think you would be hard pressed to show that neurological outcomes of vaccinates are worse than COVID patients, and that's putting it lightly. Perhaps there's a kernal of truth here that could improve the next generation of COVID vaccines, in terms of tolerability or side effects. But that's just me trying to be charitable.

(10:30) Pfizer biodistribution study submitted to Japanese regulators shows accumulation in ovaries of rats, with a 16% decrease in fertility. Fact: First, the study shows that the percent of nanoparticle lipid that goes to the ovary is less than 0.1% of the dose, compared to the injection site (roughly 25%) or liver (~15%). As for the decrease in fertility, I was unable to find a source for this claim in the limited searching I did. But I DID find a recently published study from Pfizer showing that female rats given four doses of vaccine were not different in any way from non-vaccinated rats in terms of fertility, including estrous cycle.

(15:00) Cole makes a variety of claims about immune dysregulation leading to reactivation of other viruses and increase in cancer. These claims are purely anecdotal so they are difficult to address. He mentions a study from Germany and the Netherlands, but that's not much to go on. I suspect that, like his other examples, he is extrapolating data from COVID patients and inappropriately applying it to vaccinated people.

Finally, the CDC asked me to hide this from you, but I'm going to let you in on the secret if you promise not to tell. You can find information on COVID vaccine adverse events here and here, among other places.

Conclusion
I have shown that Dr. Cole's claims about vaccines are not connected to any of the images that he showed in his presentation, and that others of his claims are either false or missing important context. It is plainly dishonest to use images of tissues damaged by the virus in order to argue that the current vaccines are dangerous. I think it is reprehensible, and even unethical, that he would claim that vaccines are ruining the hearts of children, while showing a picture of a heart that was damaged for unrelated reasons. Never does he say that these are just examples of the kind of thing he is worried about. And it is worth stating again: following Cole's argument to its logical conclusion leads to the idea that people are better off facing the virus than being vaccinated. On a population level that is clearly false.

Buried in his screed are some questions and issues that perhaps have scientific merit, but he has overshadowed and distorted them with his sensationalism and misdirection. At a certain point we leave the domain of scientific debate and enter information pollution.

Now that you've taken all of this in, go back and watch the video again and see if it still has the same punch. Hopefully, my cleanup has been worthwhile.

P.S. I've tried to make sure my ducks are all in a row in this, but please bring any errors to my attention.

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The COVID Lab Leak Hypothesis

Humans abhore uncertaintly like nature abhores a vaccum. The exact origin of the SARS-CoV-2 virus that is responsible for the COVID pandemic is still a bit of a mystery, which leaves the issue open for lots of storytelling. And what makes for a better story: that the virus arose naturally, or that it was released from (and maybe engineered by) a Chinese lab? If I were making a movie, I know which plot I would use. However, my position is like that of a lot of scientists: that a lab leak is possible, but that a natural origin is more likely. It is nevertheless amusing how adamant some people are that the virus could not have just come from nature. The issue is a complicated one, but I think this article from FactCheck.org is a nice summary: The Facts – and Gaps – on the Origin of the Coronavirus

I just want to make a few additional comments. Some have asserted that the furin cleavage site in the Spike protein is evidence that the virus was engineered. More specifically, they point out that two arginine amino acids in a row are coded by the DNA sequence CGG. The FactCheck article addresses the CGG part (and if you want to dig in further, check out this archived Twitter thread), but I want to make something more explicit.

If you look at the figure of the furin cleavage site, you will see the DNA sequence of this region along with the amino acid translation. The insertion into the SARS-CoV-2 sequence is in red and underlined. Notice that the novel sequence appears to split apart the original serine codon, moving the A (green and italicized) to the end [1]. There doesn't seem to be any logical reason for this from a genetic engineering point of view. If you wanted to insert a DNA sequence to create those PRRA amino acids, you would most likely do it in a way that didn't disturb the surrounding codons, such as what I've shown on the bottom [2]. I'm not saying that this PROVES anything one way or another. I'm simply saying that this is a weird way to genetically engineer a furin site into the protein, and in my mind it cuts against the idea.

One further point not addressed in the article is the argument that the CGG-CGG sequence results in a restriction enzyme site (FauI) that could be useful in laboratory genetic manipulations. Since each arginine could be coded by any of 6 DNA codons, that means that there are 36 possible DNA sequences to code for RR. Isn't it suspicous that this one codes for the FauI site?

I took a look at all 36 possible combinations. To begin with, there are 2/36 ways to get a FauI site. So now we're down to 1/18 vs 1/36. But more importantly, I found that an additional 15 possible codon combinations resulted in the presence of a restriction enzyme site that was as good (or better) as FauI for the presumed laboratory manipulations [3]. In other words, that FauI site isn't so special after all because if all codon combinations were equally likely, it is roughly a flip of a coin as to whether a potentially useful restriction site would be created in the RR of the furin cleavage site. And that's not taking into account additional possibilites that could be created by different codons for the flanking P and A amino acids.

So for now I end where I started. I think it is most likely that SARS-CoV-2 was transmitted to humans in a natural chain of events, but a lab leak is theoretically possible and difficult to disprove. We may never know with absolute certainty.

Notes:
1. I say 'appears' because it might not be that straightforward. The A at the end of the new sequence isn't necessarily from the original serine.
2. To be clear, I'm not saying that you would expect that exact DNA or amino acid sequence if the furin site was a product of human engineering. I'm saying that it would be spliced in differently.
3. Since FauI is a 5-cutter (i.e. recognizes a sequence of 5 nucleotides), I only considered enzymes with a recognition site of at least 5 nucleotides.

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How To Get the Church's Stock Returns

And now for something different: Today my attention was drawn to news articles highlighting the Church's U.S. stock holdings (via Ensign Peak Advisors) [1]. To my eye, the articles have a bit of a sensational air to them, intended to impress (and perhaps anger [2]) people who don't pay attention to the stock market and/or have limited financial literacy. So I thought some added context was warranted [3]. Let's take a look.

Ensign bought GameStop in Q4 of 2020, turning $870,000 into about $8.7 million, a 900% gain. Wow, what a profit!

What is $8.7 million in proportion to the size of the portfolio? Answer: 0.019%. On a normal trading day the portfolio fluctuates that much, or more, almost with every heart beat. That's like writing a news story that someone made $20 off of penny stocks as part of their $100K next egg. Also note that it's still an unrealized gain. If GameStop went belly-up tomorrow, the Church would lose all $8.7M...and the portfolio wouldn't even notice. By the way, what is GameStop's weight in the Russell 3000 index? Answer: 0.02%.

Ensign increased its Tesla stake by 39% after growing it 3,500% last year. Wow, the Church really believes in Tesla!

Again, what proportion of the portfolio is that? Answer: 0.93%. Let's compare that to Tesla's weight in the S&P 500: 1.28%. How about in the Russell 3000: 1.07%. So the Church's "agressive" purchase of Tesla brings it to a portfolio weight that is...less than in two of the major U.S. stock indicies. Still impressed?

During a pandemic year the Church's portfolio gained 16.5%, and in the first quarter of this year it has already gained 5.5% Wow, Ensign must employ some real financial whizzes. If only I could get in on the action!

Let's compare the annual and quater-by-quarter performance of Ensign to the S&P 500.

It looks to me like the Church has built a diversified portfolio that more-or-less tracks the S&P 500 [4]. The good news for you is that you don't need the whizzes at Ensign after all [5]. You can easily and cheaply invest your money in the S&P 500 or Russell 3000 using one of a number of ETFs or mutal funds.

Notes:
1. Ensign has been reporting its U.S. stock holdings quarterly to the SEC for just over a year. I assume that Ensign also holds international stocks that are not included in these reports.
2. Some people have strong opinions about how the Church manages its money. I consider it none of my business.
3. All of the analysis, and any errors therein, are mine.
4. We don't know what kind of moves Ensign makes during each quarter, so their actual returns may be more or less than it appears.
5. As a general statement, you shouldn't be trying to match the Church's investments anyway. It is a large institution with long-term goals that will make it's risk profile different than yours. In fact, it's entirely possible that the Church's overall asset allocation is too conservative for what you need.

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U.S. Excess Mortality was Not Higher in 2017

Yesterday over at Millenial Star, Geoff B. asserted that, according to a recent study, the U.S. had higher excess deaths in 2017 than in 2020. He then went on to bemoan government efforts to stop the spread of COVID and asserted that all of the worry was just media and political hype, since 2020 was less deadly than a normal year. Why, he asks, did we fall for the propaganda?

The claim that the U.S. had higher excess death in 2017 seemed unbelievable to me, but at first glance that's what the paper seemed to say. Looking closer, however, it appeared that Geoff--or whoever brought it to his attention--misunderstood the point of the study. Comments at MS are moderated and unfortunately it appears that, rather than argue the merits, my comment was rejected for unknown reasons. Luckily I saved a copy, which I have reproduced below in its entirety. Fewer people will see my explanation here, but I still think it's worth posting.

I don’t think the authors are saying what you think they are saying.

What you think they are saying: U.S. excess deaths in 2017 were greater than deaths from COVID in 2020, therefore 2020 was no big deal in comparison to 2017.

What I think they are saying: Using Europe as a mortality reference, since 2000 the U.S. has a trend of increasing excess deaths, to the point that in 2017 the U.S. lost an excess of people (vs Europe) comparable to COVID in 2020. In other words, mortality in the U.S. sucks compared to Europe. The fact that much of that excess mortality occurs in younger people, resulting in higher years of life lost (YLL) compared to the 2020 pandemic simply highlights the tragic nature of the status quo.

I offer three items in support of my view:
1. The method section states: “We estimate the number of US deaths that would not have occurred at age x, year t if the United States had the set of age-specific death rates of the European standard…”
2. A university press release that quotes the authors.
3. This CDC dashboard (scroll to the bottom) where the effect of COVID compared to other years (including 2017) is visually obvious. If you play with the options, you can find that the total U.S. predicted excess deaths (in comparison with itself, not Europe) for 2020 is 570,621 – 696,637.

So to to re-state, what we consider to be a normal number of deaths is actually an excess of deaths when compared to Europe, and the magnitude of that difference is comparable to 2020 U.S. COVID deaths.

Below is a picture from the CDC dashboard I mentioned. It shows U.S. weekly deaths beginning in 2017, with COVID deaths in blue and non-COVID deaths in green. The orange line indicates the threshold for excess deaths. Bear in mind that the highest point of the peak on the right marks the beginning of 2021, so the nunmbers for 2020 don't tell the whole COVID story. Moreover, based on provisional data, there were 3.36 million total deaths in 2020 compared to 2.81 million in 2017, with COVID as the third leading cause of death.

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Worries about COVID vaccines and infertility are ridiculous

Public Service Announcement: Claims that the COVID vaccine could cause infertility are somewhere between misguided and malicious. There is no more reason to think that COVID vaccines can cause infertility than that they could cause diabetes, or heart attacks, or arthritis, or irritable bowel sydrome, or anything else.

Vaccines are not entirely irrelevant to pregnancy. As a general rule, pregnant women are advised against vaccines that consist of a live attenuated virus or bacteria, out of abundance of caution. The the MMR (measles, mumps, rubella) vaccine stands out as one example. However, women are sometimes vaccinated before they know that they are pregnant and, fortunately, adverse effects on the fetus have not been demonstrated. Thus, the risk to pregnancy seems to be more theoretical than real. (And just for clarity, COVID vaccines do not contain live attenuated virus.)

Pregnancy aside, in the history of vaccination there have been a few vaccines that were pulled from the market due to safety problems. In the 1960s, an RSV vaccine for children was found to actually exacerbate disease [1]. In the late 1990s a vaccine against rotavirus was pulled after it was associated with a small risk of intestinal intussusception (where a segment of the intestine folds back on itself). Other vaccines have special safety considerations. The live polio vaccine, for example, is no longer used in countries with low polio risk because the virus can sometimes revert to virulence due to mutation in its genome [2]. As another example, the smallpox vaccine is still used in certain laboratory situations even though smallpox has been eradicated [3]. However, skin conditions like eczema and psoriasis pose a safety risk for this particular vaccine. The kinds of issues that I have described are well known among vaccine researchers and clinicians.

It is one thing to worry about how a live vaccine might theoretically affect a fetus, which doesn't have a functioning immune system. Similarly, I can understand being cautious when there are no safety data on pregnancy. But I cannot think of any vaccine used in the U.S. or internationally that is even suspected of causing infertility. It just isn't a thing.

There certainly are infectious diseases that can cause infertility, which leads me to a question: Why would you be more worried about a vaccine causing infertility than about the disease itself? It makes no sense. But that's probably because it isn't supposed to make sense; it's just supposed to scare.

Notes:
1. That a vaccine could make a disease worse is counter-intuitive at first glance, but there are exceptions to most rules in biology.
2. The live polio vaccine is superior to the killed vaccine in several respects, which is why it is still used in certain geographies where health infrastructure is poor.
3. It's not because they are doing smallpox research. It's because the virus that was used as the smallpox vaccine--called vaccinia--is a useful laboratory tool. Inadvertant infections can be nasty, so lab workers may be vaccinated as a precaution.

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Vaccination: What If I Already Had COVID?

Current recommendations are that people who had COVID should still get vaccinated. Does it do any good? In looking into this, I found two recently published papers (there may, of course, be others) that address this question with interesting results [1].

First, yes, the first dose of the mRNA vaccines significantly boosted the level of antibodies of people who previously had COVID. But interestingly, the second dose didn't seem to add much additional benefit.

At the same time, systemic reactions (fever, chills, fatigue, et.) to the first dose were more common in people who previously had COVID than in people with no prior exposure. Reactions to the second dose were similar irrespective of exposure history.

Does this mean that if you've already had COVID you can skip the second mRNA dose? Well, on average the data seem to point that way, although there will always be variability in the population. We don't know what the longer-term effects would be, like how long the antibody levels stay elevated. But if you previously had COVID and were miserable from the first mRNA dose, you might talk with your doctor and/or health department to see what they think.

I don't know whether or not recommendations will change based on these data. One problem is that people are often not reliable in recounting their health history. I know people who think they had COVID very early in 2020--so early that it is unlikely to be true. One person was convinced they had it in the fall of 2019! So if health officials said, "If you had COVID you only need one dose," there is a legitimate fear that we would end up with a bunch of half-vaccinated people because they self-diagnosed themselves as having had COVID. So I can't blame health officials if they just stick to two doses to help ensure everyone is fully vaccinated. But if you are really sure that you had COVID, then it might be a conversation worth having with your doctor and/or health department.

Notes:
1. Pre-print versions of these papers came out in February. However, official publication was within the last two weeks, and both can be viewed for free: here and here.

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Vaccine #2 Achieved

This week I received my second dose of the Pfizer COVID vaccine. Hooray! The next day was no big deal for me. I had some minor aching in my back and legs, and of course a sore shoulder, but if I had woken up with amnesia I wouldn't have had any reason to think that day was out of the ordinary (except for the shoulder, which was fine by the second day). Soon I will be considered fully vaccinated (i.e. second dose plus 10-14 days).

I'll be honest that things weren't as smooth for my wife. She started feeling increasingly ill the next day and developed a fever that got as high as 100.8 degrees F, along with a lot of aching (she said even her toes hurt) and chills. It hit hardest about 24 hrs after the vaccine, but after another 7 hrs the fever broke. On the second day she was feeling better, but still recovering from the soreness. By the third day she was pretty much fine [1].

It's impossible to know, but I can't help but wonder whether our respective responses to the second dose would have any correlation to severity of disease. If so, my wife would have been in pretty bad shape. Or, if it were an inverse correlation, I would have been in bad shape. Fortunately, we'll never know.

Some may think, "Well if I have a chance of getting sick with or without the vaccine, then why get the vaccine?" That's the wrong way to look at it. First of all there is the simple matter of duration. My wife was miserable for 1 day, and then it was over. People who get COVID are miserable for many days. Second, although my wife felt ill as a result of her immune system kicking into gear, there was no underlying disease. There was no virus causing damage to various organs, no loss of smell, no coughing, no extreme fatigue, and no breathlessness from simply going up the stairs. There was also no wondering when (or whether) recovery would come, worrying about whether a trip to the hospital would be needed, worrying about whether anyone else in the family would be next, or worrying about long-term effects. Other than some special cases, there is no rational risk assessment that would suggest that it's better (or neutral) to not get vaccinated.

We can't completely throw caution to the wind yet, since our 13-year-old is still vulnerable. But Pfizer has reported 100% efficacy in his age range, so I think it's probably only a matter of days before it is approved for him. At any rate, our family is close to being immune (our daughter was previously vaccinated due to some lucky circumstances--with no side effects), and I can soon go out to lunch with coworkers without worrying about getting sick myself or bringing the virus home to my family.

So my advice is to get vaccinated, but if you get the Moderna or Pfizer vaccines [2], just assume that you may need a sick day after the second dose. If your experience is more like mine, then great! But if your experience is more like my wife's, then at least you will be prepared.

Notes:
1. My wife had/has a bulging disk in her neck, so if she's not careful with her posture there is a domino cascade of muscle cramping in her upper back and a resulting headache. We think that the hunching and shivering set off that cascade, so technically on the third day she was still recovering from that.
2. I'm not as familiar with the Johnson & Johnson side effects. My wife's social media intelligence is that they are less severe, but last longer.

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Vaccine #1 Achieved

This week I received my first dose of the Pfizer COVID vaccine. Hooray! Right now, cells in my body have taken up the mRNA that was delivered by the vaccine and are producing the Spike protein of the coronavirus. Dendritic cells are starting to notice, and will make their way to lymph nodes to alert B cells and T cells that this foreign protein is in my body. Soon B cells that recognize the Spike protein will start to make antibodies--little proteins that bind onto the Spike protein whenever they come in contact with it.

In three weeks, I will receive my second dose, and the process will repeat except that the B cells that were activated the first time will really kick into high gear. At that point, my assimilation into the Bill Gates--Tony Fauci--George Soros conspiracy will be complete! (Also, I'll be immune to COVID.)

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How the New COVID Vaccines Compare to Other Viral Vaccines

The leading vaccines against SARS-CoV-2 are based on a new technology that delivers mRNA to cells. This novelty, combined with political and social division, has resulted in a fair amount of nonsense commentary about them. The AstraZeneca and Johnson & Johnson vaccines are also somewhat novel. I thought I would quickly put these new technologies into perspective by comparing them to other viral vaccine technologies.

The first thing you need to know is that the principal purpose of a genome is to store the sequence information for all kinds of different proteins. Our genome is made of DNA, but it does not directly make the proteins. Rather, a similar intermediate molecule called messenger RNA (mRNA) is produced from DNA, and it is the mRNA that is directly read by the cell's machinery to make proteins. DNA -> mRNA -> protein. (Additional variation on this scheme can be found among viruses, but RNA -> protein always holds.)

Next, the immune system can be conceptually divided into two arms that work together: innate and adaptive. The innate system responds in ways that are not specific to a pathogen (disease-causing microbe). It's what makes you feel lousy and gives you a fever, and it kicks in quick. The adaptive immune system takes longer to respond, but produces antibodies and other cells that specifically target a pathogen. The value of vaccines comes from their ability to engage the adaptive immune system such that it is ready to go when the actual pathogen shows up. When we talk about being immune to something, we're really talking about the adaptive immune response.

In order to gain immunity, the immune system needs to come in contact with components (usually proteins) of the pathogen. There are several ways of doing this. I've listed the basic strategies for viruses along with some well-known examples in human medicine. Almost all of them are also used in veterinary medicine. There are some further variations to these strategies, but I think this captures the major themes.

1. Infect someone with a weakened virus that does not cause disease. The virus commandeers the cells to produce viral proteins (via viral mRNAs). This is the oldest and classic strategy. (Examples: smallpox, measles, mumps, rubella, yellow fever, and oral polio.)

2. Inject a virulent virus that has been inactivated such that it cannot replicate. This is also a relatively old method. (Example: injected polio, hepatitis A)

3. Inject purified viral proteins. (Example: hepatitis B)

4. Inject virus-like particles (VLPs). These are essentially virus particles that do not have any genome, and thus no ability to replicate or produce more viral protein. (Example: HPV)

5. Use a different non-pathogenic virus as a Trojan horse to make proteins of the virus of interest. (Examples: the AstraZeneca and Johnson & Johnson COVID-19 vaccines are, I believe, the first approved human vaccines of this type. However, this strategy is used in a number of veterinary vaccines.)

6. Inject DNA that codes for viral proteins. DNA -> mRNA -> protein. (Doesn't seem to work well in humans, so it is not used in human vaccines. But there are a few examples in veterinary use.)

7. Inject mRNA that codes for viral proteins. This is the newest technology, first used by Moderna and Pfizer/BioNTech. The challenge of this method has been to deliver RNA to cells, since RNA is easily degraded. The technology advancement has been figuring out how to encapsulate the RNA in lipid nanoparticles such that the RNA is protected until it is delivered inside the cell.

In each of these cases, the adaptive immune system is exposed to viral proteins--proteins that were either produced by the body's cells, or were produced by cell culture prior to injection. mRNA vaccines are the cleanest vaccines in the sense that they don't involve any extraneous viral proteins or genetic material. They really get to the heart of the process: mRNA -> protein, and it's exciting to envision how they might be applied to other diseases.

Each method has pros and cons, and has to be matched to the biology of the virus and the resulting immune response. For example, in some cases antibodies directed against a single protein are sufficient to give you immunity. In other cases it's not that simple, so you wouldn't use a strategy that only delivers a single protein. But in every case, it really boils down to exposing the immune system to the right viral proteins in the right way.

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Four Years Ago: What I Got Right and Wrong About Trump

Four years ago today, on the first day of the new Trump administration, Sean Spicer called a press conference to tell lies about the size of the inauguration crowd. Here is what I then wrote:

What to Expect: A constant stream of this kind of thing, and four years of attacks on media, science, and any other sources and institutions that don't go along with his narrative of greatness, or that attempt to hold him accountable. You can especially expect him to project on others his own liabilities....

Here is my warning and plea: Do not give your mind over to his efforts to delegitimize truth. You can like his policies. You can think he's better than Hillary or Obama. Whatever. But make him earn your trust! Don't take anything his administration says at face value. [I'm grabbing you by the lapels]...don't let him (and his acolytes) control your perception of truth. You will regret it.

I think the only thing I got wrong is that not enough people regret it.

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I Was Told That Trump is Like Captain Moroni, Doesn't Seek Power

This is just a reminder that, days before the election, Sen. Mike Lee (R-UT) compared Donald Trump to Captain Moroni, asserting that he doesn't seek for power.

 “To my Mormon friends, my Latter-day Saint friends, think of him as Captain Moroni,” Lee said pointing to Trump. “He seeks not power, but to pull it down. He seeks not the praise of the world or the fake news, but he seeks the well-being and the peace of the American people.”

I expect to remind you again in two years.

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