(CNN) A new Covid-19 variant could show immune evasion and enhanced transmissibility, South African scientists warn.

COVID Winter Predictions; Napkin Calculation #6, Part 2 does not mention  a new variant; this is not yet predictable. This may change after a few years of virulent variants, or research into the potential of viable mutations. The record so far is roughly one mutation of concern per 6 months.

In COVID Winter Predictions; Napkin Calculation #6, Part 2, I wrote,

When a system of thought produces a decision as wrong in delay as the FDA decision,  it demands critical examination — of the system, not the decision.  Otherwise, the system will continue to deal out similar, deadly errors, correct in form, wrong in hindsight. No decision process should have sanctity. Figure it out.

This applies not just to boosters, but also to modification, semi de novo vaccines for a new variant. We will shortly have the results of in vitro antibody neutralization tests against current vaccines. The results will  offer preclinical estimates of vaccine immunity evasion. If the tests show  current vaccines neutralize Omicron/B.1.1.529,  the story ends here.

If Omicron evades current vaccines, the story continues, with vaccine development a hybrid of now-tested platforms against a new target, spike protein with an unprecedented number of mutations. The clock starts in a race between enhanced COVID mortality and the risks of partly de novo vaccines. The booster question was decided in strict accordance with FDA protocols, delaying rollout relative to feasible, with the yet-to-be-seen consequences.

Let’s explore what may become a real world sequence of administrative decisions in vaccine development for Omicron:

• In vitro tests imply antibody evasion.
• Case-control studies look at vaccination history of individuals with Omicron infection, for confirmation of in vitro tests.
• Omicron continues to spread, confirming real-world selective pressure for the variant.
• Vaccine makers select spike protein targets. Small quantities of antigens are made, to test against Omicron in the dish.
• Pilot (small scale industrial) vaccine production.
• Animal trials, then human.

Moderna partially and ethically overlapped animal/human, with Stage 0 human trials – can-it-work?, before completion of animal trials.  (Stat) Researchers rush to test coronavirus vaccine in people without knowing how well it works in animals. It saved lives, a potential example of foreshortening strategies. Stages 1,2, and 3 follow, double-blind, where neither the participant or the investigators know who got the shot and who got the placebo until the stage is unblinded.

• Stage 1 safety trials on volunteers with ethical consent.
• Stage 2 trial, does it work?  Months elapse as the study cohort is followed until statistical confidence is obtained.
• Stage  3, efficacy compared to no or other vaccine.
• Mass production/EUA, or EUA/mass production.

There is risk, and opportunity to save time, by overlapping stages. Techniques of data fusion, applied to multiple stages and studies, can shorten time to statistical significance. In Operation Warp Speed, the big players were capitalized to risk mass production before EUA, risking only money.

Before EUA, the risk of skipping/overlapping steps is limited to study volunteers, and financial loss. The public remains at risk to  COVID.  If in vitro tests were accepted as temporary proxies for case-control studies, several months could be gained, at no risk.

The delay by the FDA of boosters, with implications for Omicron, signifies blind adherence to what Hippocrates never said: “First, do no harm.” We need sighted adherence to the same: First, do the least harm and the most good. Within our sight is one question, which may cut the knot, leaving the remaining risks, of the vaccine platforms, pretty well known and tolerable.

The mRNA vaccines cause cells within the recipient to  produce fragments of spike protein as the antigen, in the case of Omicron, a highly mutated form.  Spike protein is  toxic. (PubMed) Be aware of SARS-CoV-2 spike protein: There is more than meets the eye.

Released into tissues unbound to an adjuvant, spike protein fragments have higher mobility than the antigen of a typical protein based vaccine, diffusing through body tissues. The vast majority of mRNA recipients have experienced no untoward side effects. While the current mRNA vaccines are an unqualified success, the Omicron spike protein is an unknown risk factor.

Is there a way to telescope this risk evaluation into a smaller interval than typified by FDA protocols? One stratagem is very high dosing of animal models,  including higher primates, such as the African Green Monkey. (Nature) Animal models for COVID-19.

We will shortly know if the Omicron clock has started running. Vaccine researchers will undoubtedly identify more issues. Omicron may require the fullest exploitation of knowledge to shorten the development cycle, to abide a sighted version of the Oath:

First, do the least harm and the most good.

We continue from COVID Winter Predictions; Delta+/AY.4.2; Prediction Follies, Part 1.

This paints a picture:

• (CNN video) WHO Official: It’s too late to prevent another Covid wave in Europe
• (CNN) Germany’s Covid cases hit record high with Merkel warning of ‘dramatic’ situation.
• (CNN) Ireland, home to one of Europe’s highest vaccination rates, imposes curfew on pubs and clubs as cases rise.

A picture of the failure of COVID vaccines to benefit public health in the way they benefit the individual, which is indisputable. While medical knowledge of the disease is significant and growing, it paints a picture of almost total ignorance of the epidemiology of COVID. The distinction is important, since the medical profession is under siege by a large contingent of the public who have descended to idiocy, exacerbated by unscrupulous politicians and social media.

Quoting from COVID Winter Predictions; Delta+/AY.4.2; Prediction Follies, Part 1,

This is one of those occasions where it is constructive to undermine. To allow the predictions to remain unchallenged invites possible public health whiplash, as happened with (CNN, 2021/05/14) The CDC says masks are no longer needed inside or out if you’re fully vaccinated. By now, we should realize that COVID has more fake-out moves than the Harlem Globetrotters.

A model is a means to simulate a real world process, usually on a computer, sometimes on a napkin. The current state of the art, COVID-19 ScenarioModelingHub, Round 9, takes as input the plateau-uptick that began on 10/23/2021. But as of  11/20-present, the uptick barely registers in the predictions. In isolation, you may be forgiven your trust. But you can’t ignore Europe, which is not fundamentally different from the U.S. A sinking suspicion invades your brain: You can do better reading the news.

The predictions of COVID-19 ScenarioModelingHub, Round 9 look no better, and possibly worse, than a math technique that dates to about 1960, the linear Kalman filter.   In the 60’s, this mainstay of systems engineering was a game toy, used to predict things like weather, for which it should not have worked at all. It worked better than nothing.

I’m not going to bother you with the meaning of “linear”, except to note that many problems can be broken into linear pieces. This is why the ScenarioModelingHub models seem to work — until there is a change in the trend. The inability to predict a change in trend is characteristic of a bad model. Only the simplest part of the models work, the crude linear approximation. Garbage in, garbage out. 

Our napkin calculations are guilty of same, but they make no pretense of accuracy.  The wisdom of John von Neumann applies: “There’s no sense in being precise when you don’t even know what you’re talking about.” A napkin calculation is not to be believed, but usefully undermines pretenses of sophistication.

Let’s enumerate recent public health pronouncements for contradictions:

• Two shots are all you need. This was recently turned on its head.
• Cell mediated immunity, plasma cell growth, and antibody quality continue to improve long after antibody titers decline, providing durable protection. On its head.
• The reproduction numbers, R_o and R, are useful in prediction modeling. False beyond trivial napkin calcs.
  
• A vaccination sequence that works when people stand 6 feet away works when people stand 3 feet away. Numbers, breakthrough versus distance, versus date of vaccination, unknown.
• Three shots are all you need. Doubtful.
• Breakthrough cases are  minimally infectious. Correctness,  with normal waning of immunity is  unknown.
• When, after this winter, in analogy with  German Health Minister Jens Spahn, (CNBC) “probably by the end of this winter, pretty much everyone in Germany will be vaccinated, recovered or dead…”, we will finally be done with COVID. Doubtful.
  
• COVID is like other respiratory diseases. Manifestly false. It seems to re-arm after a short interval.
  
• Herd immunity will happen. Not to the extent you might hope.

Taking note of this poor state of knowledge, we paint what went wrong with a broad brush.

Empirical. Diligence in social distancing has declined. At the Willow Grove, PA Home Depot store, 80% of employees faked the wearing of masks, nose uncovered, or around their necks. At the Moreland Road Walmart, 50% compliance was observed.

Theoretical.  Quoting Becker’s Hospital Review) States ranked by percentage of population fully vaccinated: Nov. 23,

“As of 6 a.m. EDT Nov. 22, a total of 196,398,948 Americans had been fully vaccinated, or 59.2 percent of the country’s population, according to the CDC’s data.”

Not anymore, they aren’t. In the crude world described by John von Neumann, where we don’t know what we are talking about, cut that in half, to 30%. It will do for argument. Now dredge up Napkin Calculation #4, which resides at (CNN) White House frustrated with Irresponsible Delta Variant Coverage…Napkin Calculation #4. The relevant equation:

• • Effect of a vaccine: R = R_o * (breakthrough%)/100.

With loss of social distancing, we have to pick a number for R_o. Estimates have been as high as 9. (Journal of Travel Medicine) The reproductive number of the Delta variant of SARS-CoV-2 is far higher compared to the ancestral SARS-CoV-2 virus offers the result of a survey, R_o = 5. Since some people are still wearing masks properly, let’s fold it into R_o, as R_mask = 3.5, so we can see what the vaccine does.

Now pick a breakthrough rate for the poorly vaccinated U.S. population. 70% breakthrough is plausible. Reduced immunity from aged vaccination status may tamp down mortality, but many breakthroughs will experience the worst sickness in their lives. Let’s plug in the numbers:

• • For Pfizer, possibly Moderna, and Delta, R = 3.5*( 0.7) = 2.45. Disaster!

On July 10, I began to agitate for a booster: Pfizer versus FDA & CDC; Booster Shot Needed Sooner than Later. On July 12, Pfizer Booster is Needed? Breakthrough Case Infectivity; Managing Public Health Communications. Quoting from  {9/15) FDA advisers consider Covid-19 booster shots Friday, 

So why the resistance? FDA/CDC are constituted to render decisions of the kind that A nationwide study… presents fact in the state of Israel. Nothing in the FDA/CDC charters permit rubber-stamping the authority of another national establishment, even one as competent as Israel.

Following form, and the requirements elucidated by Drs. Philip Krause,  Marion Gruber, and Paul Offitt, for evidence based medicine,  the FDA did not approve a booster. On 11/19, they approved boosters for everybody, though 6 months after the 2nd shot may not be timely.

When a system of thought produces a decision as wrong in delay as the FDA decision,  it demands critical examination — of the system, not the decision.  Otherwise, the system will continue to deal out similar, deadly errors, correct in form, wrong in hindsight. No decision process should have sanctity. Figure it out.

If I was prescient, napkins deserve the credit. Napkin calculations facilitate mental flexibility, because they are so easy to change. The models of ScenarioModelingHub are enormously complicated, involving automated data collection, normalization, and complex calculations. The modeler becomes a slave to the model.

As for the rest of us, we can free ourselves.

 

 

 

 

 

 

 

 

 

(CNN) Pence says he looked to James Madison as he certified the 2020 election for Biden. Quoting,

Asked during an event at the University of Iowa who had told him to buck Trump’s plan, Pence responded, “James Madison.”…The former vice president also cited the Bible, saying, “Psalm 15 says he who keeps his oath even when it hurts.”

What did Pence mean? I thought the media would engage constitutional scholars  for a view of the inside of Pence’s head. But they didn’t, leaving Madison’s contribution in the shadow of Dolly Madison’s purported introduction of ice cream to the White House.

Madison is thought to have written 29 of the 85 anonymous Federalist Papers, widely considered the most important political texts of U.S. democracy. Pence most likely referred to No. 51, written by either Hamilton or Madison, The Structure of the Government Must Furnish the Proper Checks and Balances Between the Different Departments. The lack of formatting makes the  .gov versions  hard to read. Alternate sources are publicly available; see (The Avalon Project) No. 51. A formatted version with interpretation: (Bill of Rights Institute) Federalist Papers No. 51 (1788).

I re-read  No. 51, picking at it as Pence may have. The likely interpretation comes out of  textual order. The problem: The executive branch might seek to be self perpetuating, a form of dictatorship. Quoting,

Ambition must be made to counteract ambition…If men were angels, no government would be necessary. If angels were to govern men, neither external nor internal controls on government would be necessary. In framing a government which is to be administered by men over men, the great difficulty lies in this: you must first enable the government to control the governed; and in the next place oblige it to control itself.

In the pivotal moment, Pence, as President Pro Tempore of the Senate, saw his obligation as control, as check on power.  Though he did not have No. 51 in hand, he backed up a few hundred words, and recalled,

In order to lay a due foundation for that separate and distinct exercise of the different powers of government, which to a certain extent is admitted on all hands to be essential to the preservation of liberty, it is evident that each department should have a will of its own; and consequently should be so constituted that the members of each should have as little agency as possible in the appointment of the members of the others.

By implication, it should not be a power of Congress, the legislative branch, to select the President,  head of the Executive Branch.

The Federalist Papers are not law.  They are essays written by some of the framers of the Constitution, providing insight into their intent not visible in the terse text of the Constitution. A scholar or jurist of  “strict construction” literalness might never refer to the papers in opinions. More interpretive jurists often refer to the Papers.

Mike Pence, arch-conservative,  chose to immortalize the intent of the Founding Fathers in tandem with their creation, the Constitution of the United States.

You may or may not like the political views of Mike Pence.  Yet history will grant him this: He was the man of the hour. 

Thank you, Mike.

 

Everyone is free to scrape the blog as much as they want. Please scrape slowly, one per minute, so as not to impede other users. You will not be blocked unless you overload the system.

(CNN) Russian diplomat found dead on street outside Berlin embassy. Quoting,

The death of the diplomat came nearly a year after an investigation by CNN and Bellingcat revealed that an FSB toxins team of about six to 10 agents trailed Russian opposition leader Alexey Navalny for more than three years before he was poisoned in August 2020 with the lethal nerve agent Novichok.

An excellent factual summary: (Bellingcat) Russian Diplomat Who Died at Berlin Embassy is Senior Intelligence Figure’s Son

Limited by policy typical of reputable news organizations, CNN does not directly speculate that the diplomat/spy was executed. With the understanding that what follows is speculation informed by precedent, we can be more direct.

With the notable exceptions of Vitaly Yurchenko and Oleg Gordievsky,  the sanction for Soviet/Russian nationals guilty of treason has been death. Yurchenko escaped punishment because his cover story had propaganda value that would have been destroyed by disclosure he had been an ambivalent traitor.

Gordievsky, a double agent, ultimately escaped punishment with exfiltration by British intelligence. (Haaretz) How Double Agent Oleg Gordievsky Changed the Course of History.

Gordievsky’s survival had another factor. Perhaps in response to the horrors of the Stalin era, the post-Stalin KGB developed a standard of internal adjudication with some of the protections customary in the West. The KGB did not prejudge traitors in their ranks. In 1985, in an informal weekend retreat, Gordievsky was interrogated with remarkably effective truth drugs. As the drugs produce complete amnesia, Gordievsky himself would not have known what he said. As his personality is controlled rather than impulsive, it is possible he did not reveal enough for conviction by then prevailing KGB standards . He was blacklisted, set free, then exfiltrated.

During the Stalin era, many executions occurred in the offices of superiors; post-Stalin, with more formalized adjudication, in prisons. There was little need to terminate a double agent in the target country; the double remained tied to the motherland by cultural distance from the West, with family held hostage to loyalty.  Soviet tradecraft was excellent, which meant that  a Soviet double had the skills to avoid detection until fingered by a U.S. double, such as Aldrich Ames.

This skill also resulted in lack of awareness by the double that he had been fingered. He would simply be called back to Moscow on pretext, subjected to a trial/interrogation which obtained the important “confesssion”, and legally executed. Now that tradecraft has crumbled, there is a reasonable possibility a double knows he has been detected, and will bolt, escaping punishment.

Bellingcat:

…the diplomat was the son of the deputy director of FSB’s Second Service and the head of the FSB’s Directorate for Protection of Constitutional Order, Gen. Alexey Zhalo. …As previously reported by Bellingcat and its partners, the FSB’s Second Service has been linked to the assassination of Georgian asylum seeker…

It is natural to wonder if the son was in the same line of work as his father. While nepotism remains strong, and the post would have formerly  been part of the nomenklatura, this is unlikely.  Germany is sufficiently porous there would be no need to cloak “assassin supporting services” with diplomatic cover.

His real  job, with cover of  “second secretary”, likely involved contact and recruitment in the German government. He may have decided to go double. Sadly for him, Germany is so permeated with Russian spies that the person he approached may have been an agent for Russia, who fingered him.

Why did the Russians not call him back to Moscow on pretext?

• He could have known he was fingered, the consequence of poor compartmentalization — tradecraft.
• He could have been warned by his father.
• His father could have assented, to avoid the stain.
• He could have been acting for his father, as a conduit to the West.

Hence the necessity of execution on embassy premises, before he could bolt. Watch for the untimely demise of Gen. Alexey Zhalo.

 

 

 

 

Mop and Broom  escape by the light of the silvery moon! (Read down.)

(Click to enlarge.)

Wherever they end up, let’s hope the detergent is gentle and the soap has a delicate scent. Love triumphs over all, the saying goes. In actuality, only in movies, animation, and song:

By the light of the silvery moon