We continue from COVID Resurgent: Of Hares and Foxes; Primer for Policy Makers, Part 3., which poses a list of questions.  With our Houston Astrodome experiment, we explored the natural balance between the predator (virus) and the prey (host, you.) We saw that in the extreme, mutual extinction could occur.  While this may have happened unobserved, the closest known example is a transmissible cancer that affects the Tasmanian Devil, an Australian marsupial.

The first question of our list is:

• How can a virus appear to have an intelligent strategy, when it isn’t even alive? Does Darwin’s theory of natural selection play a role?

If you think the mind has a monopoly on thinking, try to put this notion aside temporarily. When you think about a problem, you try to imagine all the ways it could turn out. At the level of atoms, molecules, viruses, and heredity, Nature tries combinations at incredible speed. The result appears thoughtful. Maybe it is.

So Nature rolls the dice constantly. The processes by which a virus or cell or any form of life reproduces has the chance of error. We call this error mutation.  The result of constantly occurring mutation is genetic diversity.

Genetic diversity is key to the survival of a species. Without it, the human species would already be extinct, killed off by something like COVID. This diversity prevents a virus from knowing its prey too well. It’s the difference between a burglar who has cased the joint, and one who hasn’t.

Genetic diversity saves us from one outcome of the Astrodome experiment. If the foxes are super-efficient at hunting rabbits, they kill off their food supply.  Both go extinct. But rabbits are wily and evasive. The foxes can’t catch all of them.

Genetic diversity is responsible for an axiom of infectious disease: No disease is 100% fatal. Rabies was thought to be. A few years ago, a young woman walked into a Texas hospital with rabies. With no specific treatment, she walked out three weeks later.

Likewise, if a virus did not mutate, the prey would develop universal immunity, so the virus would go extinct.  Mutation comes easily to RNA viruses like COVID, because RNA is fragile.  DNA is so tough you could make golf club shafts out of it. Yet mutation is so important, even DNA viruses roll the dice. (Science Daily) How poxviruses such as smallpox evolve rapidly, despite low mutation rates.

The viral mutations we see are the ones that enable one strain of COVID-19 to out-compete other strains; this is Darwin’s natural selection. Selection works on humans too, but we want to prevent it with medicine and public health policy.

We have addressed the first question of our list:  Even though they cannot think, viruses and immune systems have strategies that appear thoughtful.

The human race will survive COVID. But we want to prevent a Darwinian outcome.  And you’ve got some personal skin in the game.

Our next question: What drives virulence, and what holds it back?

 

 

 

 

With countless plaudits honoring the work of Ruth Bader Ginsburg, what can I add?

There is a folk expression to the effect that with every passing year, the personality is more deeply etched upon the face. By age 87, her personality was in clear display.

She was kindly, yet fiercely determined.

So many strivers are driven by  ambition. Hers was a calling, a vision of principles.

Like cellist Pablo Casals, who improved every year before he died,  Ruth Bader Ginsburg was born a mortal, and died a giant.

We need her still. Who will champion “Be all you can be”?

Although the opinions of a Supreme Court justice, even in dissent, tend to be monumental, I can’t think of her by other than her first name.

Thank you, Ruth.

Let’s see if we can find a smoking gun. To follow this, you need to read (CNN) AstraZeneca pauses coronavirus vaccine trial after unexplained illness in volunteer. Follow the links back.

(CNN) NIH ‘very concerned’ about serious side effect in AstraZeneca coronavirus vaccine trial. Quoting,

“The highest levels of NIH are very concerned,” said Dr. Avindra Nath, intramural clinical director and a leader of viral research at the National Institute for Neurological Disorders and Stroke, an NIH division. “Everyone’s hopes are on a vaccine, and if you have a major complication the whole thing could get derailed.”

The Oxford- Astrazeneca vaccine belongs to the most aggressively novel class of new vaccines: It transfects cells in the recipient with a vector, a carrier virus, to cause them to make COVID spike protein. For a COVID vaccine, transfection  means:

• Deliberate infection of cells near the injection site with an engineered virus, the vector.
• Transport of spike protein DNA into the cell.
• Modification of the cell machinery to make COVID spike protein.

The virus particles of the Astrazeneca vaccine are active micro-machines. This is not as radical as it sounds. Live-virus vaccines were the first devised. They are still used today. Some, such as the live virus polio vaccine, or yellow fever 17D, have known hazards. But in comparing with live virus vaccines of the past, there are meaningful differences:

• Trials were over a much longer period.
• Trials defined age groups, typically juvenile, when the immune system seems to handle well challenge with live virus.
• These vaccines contain large amounts of virus, easy for the immune system to spot, and weakened by multiple passages through nonhuman tissue, cold adaptation, or chemical degradation. This goes back to Pasteur.

There is no rigorous argument for why weakened live virus is usually safe, but it has 150 years behind it. AstraZeneca’s argument is weak, and they have about 3 months behind it.

Is the Astrazeneca event a random event or a smoking gun? Let’s see if we can smell smoke. Details of the event are important, not to establish fact, but possibly requiring the trial be halted.  Let’s begin with rabies, a virus with a stealth trick:

• Somebody gets bit in the deltoid muscle, where you would get the shot. Most immunizations inject into the deltoid muscle of the upper arm.
• Virus in the animal’s saliva incubates silently in muscle for weeks, months, or years. In perhaps 1/3 of bites, it evades the immune system.
• The deltoid muscle is served by the axillary nerve, which, combined with other nerves, exits the spine at the base of the neck. In the deltoid, the nerve has little bulbs, neuromuscular junctions.
• If the rabies virus has evaded the immune system, it breaks into the junctions. It then travels up the nerve, the spinal cord, and finally the brain, where it causes rapid death.

Besides rabies, any virus which incidentally penetrates a neuromuscular junction, or penetrates the brain in some other way, has a chance of infecting the nervous system. Once inside the nervous system, a virus is partly shielded from the immune system, which is why a virus like West Nile can be innocuous or fatal.

So a virus  that does not normally cause encephalitis can be big trouble if it gets into the brain. In a child who has not been vaccinated, measles can cause subacute sclerosing panencephalitis, invariably fatal, with a timeline unaddressed by COVID clinical trials.

Suppose somebody gets the Astrazeneca shot, and the tip of the needle nicks a neuromuscular junction, and virus gets into the junction. The vaccine contains two viruses. One is the Kamikaze, which carries the payload, spike protein, into the muscle cell target. Traces of the helper virus are also present.  But how does a virus which has no experience with nerves know how to climb the axillary nerve all the way to the cervical vertebrae, where it might cause transverse myelitis?

A virus doesn’t have to know a thing. The axillary nerve contains a conveyor belt, reverse axonal transport. Hooked onto the conveyor, even completely inert particles will reach the brain. This was shown years ago by an experiment with patients who had a few days to live. Colloidal gold was sprayed into their noses. When the patients died three days later,  their brains were sectioned, and the gold was found.

The rumored  adverse event is transverse myelitis. Instead of a lesion extending up, down, and sideways, it mainly goes sideways. It’s like nerve block anesthesia, which affects function below the the block. The lesion extends across the whole spinal cord near a few vertebrae. With the Astrazeneca patient, we would expect to see symptoms of a spinal lesion around C5 and C6, the lower cervical vertebrae, at the base of the neck.

This is the smoking gun. If the lesion is not around C5/C6, it could still be the vaccine, but we don’t smell smoke. We would have to consider more typical causes, such as autoimmunity caused by the vaccine. This too has happened.

Are the symptoms caused by the Kamikaze virus, or the helper virus? This is hard, but important. The Kamikaze cannot reproduce, so it cannot cause a slow virus infection, like subacute sclerosing panencephalitis. The helper virus, though present only  in trace amounts, can reproduce. There is a questionable presumption of safety.

This  scenario pertains to vaccines that use a virus to  penetrate cells in the recipient. It cannot happen with:

• Killed virus vaccines.
• VLP (virus-like particle) vaccines.
• RNA vaccines.
• DNA vaccines.

These vaccines have similarity-to-safe; for what this means, see Why I Defend FDA Commissioner Stephen Hahn. A single live-virus vaccine in use today, 17D for yellow fever, can cause fatal infection. See Moderna Partial Results Part 1.

Whether a vaccination can introduce live virus into neuromuscular junctions was not formerly a troublesome question. Now it is. Rigorous safety demands an answer to: Why did this  adverse event happen? It cannot be well studied in humans, because the spinal cord of a living person is not available. It can be studied in animals in a far more detailed way. The answer will not come quick.

So do the right thing.

 

(CNN) AstraZeneca pauses coronavirus vaccine trial after unexplained illness in volunteer. Quoting,

“In large trials, illnesses will happen by chance but must be independently reviewed to check this carefully. We are working to expedite the review of the single event to minimize any potential impact on the trial timeline. We are committed to the safety of our participants and the highest standards of conduct in our trials.”

Chance is one possibility. For another, see  Why I Defend FDA Commissioner Stephen Hahn. Quoting,

This sounds informative, but it leaves out a crucial safety question, discussed in Why I Would Not Take the Russian or Oxford – AstraZeneca Vaccines – Part 2. Quoting the nut of it,

After a while, we’re ready to harvest the culture medium for the virus we want, the Kamikaze, purifying it of the helper virus. We don’t want the helper virus in our vaccine, because it  does not contain the code for the spike protein, and it can replicate…

Very small quantities of live, helper adenovirus are present in the finished vaccine product.  Supporters of these vaccines make these claims:…

(Reuters) Putin critic Navalny was poisoned with Novichok nerve agent, Merkel says. Quoting,

She said Berlin now expected Moscow to explain itself and that Germany would consult its NATO allies about how to respond, raising the prospect of new Western sanctions on Russia, sending Russian asset prices tumbling.

You read it here first:  Alexei Navalny, Poisoned Again? The Russian Poison Trick. Quoting,

The modern syndrome is near-death, prolonged illness, partial recovery, and prolonged or permanent disability. It is characterized by stealth and extreme precision,  a sub lethal dose of a  substance so poisonous it completely evades standard toxicology. Vil Mirzayanov revealed the existence of the Novichok family of nerve agents in 1992, but hope for a “new Russia” delayed assessment of the threat.

You read it here first, and there isn’t a subscription fee!

But you might have guessed as much if you read (NPR) Navalny Was Poisoned, But His Life Isn’t in Danger, German Hospital Says. Quoting,

Navalny is now being treated with an antidote called atropine; the medical team says there’s the possibility of long-term effects on his health and particularly his nervous system.

Treatment with atropine as the only named substance suggests a partial truth. Atropine is only part of a treatment protocol. Additional chemicals are required to reactivate cholesterinase, and scavenge loose  Novichok. According to the inventors of Novichok, the bond is much harder to break than with VX. The Russians considered Novichok exposure to be untreatable, except for supportive care.

Since Porton Down chose not to disclose the protocol that saved the Skripals, it is reasonable to suspect that Charité Hospital told a little white lie, to protect British innovation.

How did the Germans or Brits determine the poison? The Raman microscope, with the ability to perform spectroscopy on  microscopic quantities, is probably involved.

 

 

Edit: Dr. Fauci’s remarks in KHN interview.

(CBS) COVID-19 vaccine will be made available “on the basis of science and data,” FDA commissioner says.

Suspicion says Hahn is under pressure to approve a vaccine before completion of Phase 3 trials. I have been writing articles about caution with new vaccines. This is about the other side of the coin.

Clinical trials are supposed to safeguard reason with the power of statistics. In the minds of the public, and possibly you, they are a complete replacement for something they have no understanding of. This is natural. It’s also a kind of intellectual poison.  There is no replacement for intellect, except to rely entirely on expert judgment, which you might fear is caving to political pressure.

In a court of law, expert witnesses for the prosecution and defense compete for the minds of the jury. We think this works better than the alternatives. It could work better here.

If you are interested in Hahn’s decision making process, how he thinks, you have to go beyond trials-phase 1,2,3. Plans, procedures, and  statistics cannot replace human reason.   Human intelligence connotes adaptation to circumstances as they evolve. You have to understand Hahn’s intelligence, which requires a little more about vaccines than the media provide.

With apologies to Reuters, look at Scientists see downsides to top COVID-19 vaccines from Russia, China. Quoting,

Researchers have experimented with Ad5-based vaccines against a variety of infections for decades, but none are widely used. They employ harmless viruses as “vectors” to ferry genes from the target virus – in this case the novel coronavirus – into human cells, prompting an immune response to fight the actual virus.

This sounds informative, but it leaves out a crucial safety question, discussed in Why I Would Not Take the Russian or Oxford – AstraZeneca Vaccines – Part 2. Quoting the nut of it,

After a while, we’re ready to harvest the culture medium for the virus we want, the Kamikaze, purifying it of the helper virus. We don’t want the helper virus in our vaccine, because it  does not contain the code for the spike protein, and it can replicate…

Very small quantities of live, helper, adenovirus are present in the finished vaccine product.  Supporters of these vaccines make these claims:…

Don’t trust me. Read the abstract of (PubMed) Evidence of frequent recombination among human adenoviruses. With elisions so you can see the point:

Genome stability is a prerequisite for the production and use of adenoviruses for therapy of genetic diseases and cancer….Our results suggest that recombination among circulating adenoviruses is very frequent and plays an important role in shaping the phylogenetic relationships of adenovirus genomes.

This line of reasoning now presents:

• For adenoviruses to be used, they must be stable.
• Adenoviruses frequently recombine. Hence they are not stable.
• Adenoviruses must not be used.

This is similar to unsafe. Maybe this makes you uncomfortable; you’d like to disengage. It’s not your specialty, you don’t know anything about it, so you’d rather rely on experts, who you don’t trust either. But you can’t disengage, because you are a juror in the court of public opinion.  With or without you, there will be a verdict, You may as well help it be a good one.

So how do you use the above? It’s  an argument, not a fact. You can show it around to prospective “experts”. And like a juror, you might see something in a face, a tone, or a gesture that inclines you to doubt. Or you might find their reasons  unconvincing.

A while back, I’m embarrassed to say, I cited the Thorotrast debacle as preventable by thorough clinical trials. It is actually exactly the opposite. It’s an example of a disaster that could have been prevented only by human reason, because the cancers produced by Thorotrast take 20+ years to develop.

The only way the Thorotrast disaster could have been prevented is by recognition, in radioactivity introduced into the body, of similarity to unsafe. In this phrase, we stumble on what a court would call professional expertise. An expert should have the ability to recognize  two basic similarities:

• Similarity to unsafe. “It looks dangerous.”
• Similarity to safe. “It looks safe to me.”

Similar to unsafe should require extensive, prolonged, exacting investigation in every avenue of potential hazard. Novelty enhances this similarity. Familiarity, or precedence of use, reduces it.

Some novelties remain similar to unsafe, because the current state of knowledge does not resolve the difference. (PubMed) Evidence of frequent recombination among human adenoviruses offers no more foundation than quicksand.

Similar to safe requires another faculty embedded in professional expertise, using what we call good judgment to abbreviate investigation. Influenza strains mutate yearly. But vaccines manufactured by established processes do not repeat clinical trials. They are accepted as similar to safe.

By now, you should have one  takeaway: Vaccine safety is not served by a mechanical process, 1,2,3.  That process is a theme with variations, working in concert with expertise, which unlike the scientific method, still resists bottling.

What are Commissioner Hahn’s choices? The nearest term options are controversial ones, to approve a vaccine that has completed:

• Phase 2 or 3, but highly novel, with a similarity to unsafe.
• Phase 2,  but less novel, with less or no similarity to unsafe, with high immunogenicity.
• Phase 2 or 3, which appears inherently safe, but less immunogenic, and hard to store and transport.

Hahn knows that within 6 months of the above, more and probably superior options, free of traces of live virus, will have completed phase 3. During the wait, people will die.

Dr. Fauci has another criteria. (Kaiser Health News) There’s a legitimate way to end coronavirus vaccine trials early, Fauci says. Quoting,

The Data and Safety Monitoring Board could say, “‘The data is so good right now that you can say it’s safe and effective,'” Fauci said.

Yet  numbers do not replace  judgment and ethics.  A vaccine could reduce fatalities, with unapparent change in average severity. What of  the risk that the trace helper virus of an adenovirus vaccine does something horrible long after clinical trials? Are ethics served by immediate need or unknown risk?

With a little effort, and a little help from the media, you can think along with Hahn. And maybe, when he makes a decision, you won’t have to cry “foul!” The jury is still out, and you’re on it.

Will the media step up? These are tough times for the inquiring mind.