The New Vaccines, DNA "damage", and Infertility

With the previous discussion on basic vaccine mechanics under our belts, we can now consider what sorts of dangers these vaccines might entail.

Can a vaccine cause a systemic problem in the body because of DNA damage of some sort?

The oldest type of vaccine, which is simply a milder disease, replicates throughout the body and--as viruses do--modifies and "damages" DNA in cells throughout the body as it does so.  So, there is some danger of systemic damage throughout the body.  But DNA damaged cells are disposed of throughout the body all the time, so this isn't usually a big deal.  Cells die and are disposed of naturally; even mild diseases like the cold "damage" DNA and cause more cells to die and be disposed of all the time and no one thinks twice about it.

More modern vaccines are not a milder disease, but rather an attenuated form of the disease: neutered virus particles.  It is *intended*  that the effects of these virus would be limited to a smallish number of cells because the virus replication ability has been (hopefully) mostly destroyed by whatever the neutralizing procedure was (UV lighting or something else).  How well you can trust that only a limited number of cells will be effected depends on how well you trust this attenuation process.

Adenovirus vector vaccines (AstraZeneca and Johnson & Johnson, among others) certainly do "damage" the DNA of cells at the injection site, by design.  They are limited to a set number of cells which they effect because their replication ability has been genetically removed.  How well you can trust that only a limited number of cells will be effected depends on how well you trust this genetic alteration.

Finally, the mRNA vaccines (Pfizer and Moderna) don't affect DNA at all.  They cause the production of spike proteins without needing virus particles at all; they deliver mRNA to the cell via mini lipid drops rather than via a virus of some sort.  mRNA vaccines are therefore absolutely incapable of reproduction, no matter what the circumstance.

Bottom line: new vaccines are less likely to cause systemic problems than older vaccines, because they are more precisely targeted to specific effects.  None of them, though, have a built-in mechanism that would cause a systemic problem throughout the body, despite some of them working via DNA.

How could a vaccine cause problems with infertility?

DNA "damage" is therefore not an issue, but that doesn't mean there is no mechanic by which a vaccine might cause some body-wide problem.  Almost all plausible mechanics of that sort are related to the immune response to the vaccine, however, not the vaccine itself (which only exists in the body for a short time).    Here's how something like infertility could potentially be caused by a vaccine:

As mentioned, the body's immune systems learns how to produce virus-specific neutralizing antibodies.  As we have also seen, sometimes these antibodies are not actually specific to a single virus--and this is sometimes the point.  The cowpox antibodies happen to match the smallpox viruses as well, which is why cowpox infection ends up in smallpox immunity.

The danger then exists that the body will produce antibodies in response to a virus, or in response to a vaccine, that will attack something good as well as the virus that it is intended to attack.  This is the mechanism by which it has been theorized that a vaccine could interfere with fertility.  There is a protein called "syncytin-1" that is used in the placenta, and it happens to have small stretches of genetic code that are similar to parts of the code for the spike protein of a coronavirus.  What if this similarity is enough that the antibodies produced against the spike protein are also able to attack syncytin-1?  This would, in effect, create an auto-immune response to the placenta and prevent or imperil pregnancy.

While not impossible, this scenario is very unlikely, for several reasons:

1. The amount of similarity between the proteins is actually quite small.  I know that scientists nowadays are actually pretty good at determining how likely it is that you can get cross-reactions between different proteins based on genetic structure.  I'm not aware of an actual study in which the similarities between syncytin-1 and the spike protein were computer-analyzed to estimate *how* similar they would be, but if you hear scientists say that the similarity is too small to matter, they probably have good reason for saying that.
2. Pfizer actually has some data on pregnancy from its phase 3 trial data.  No trial participants were recruited who were pregnant, but some became pregnant in the course of the trial.  Pfizer had 12 people who took the vaccine end up getting pregnant and 11 people who took the placebo end up getting pregnant.  This is a good indication that no effect on fertility is to be expected from the antibodies.
3. If the vaccine caused infertility, it would be because of the immune response and not the vaccine per se.  This means that recovering from Covid-19 itself would also cause infertility, because it would be the immune system's antibodies that would attack syncytin-1.  Worldwide, there have been about 95 million reported cases of Covid-19.  We're pretty sure that this is a large understatement of the total number of cases, and that there are a lot of people who had mild or no symptoms who are not accounted for by that number.  These people would also have generated these neutralizing antibodies.  So there should be something like 200 million people out there at this point who have neutralizing antibodies to the Covid-19 spike protein.
   
   If that many people were out there with antibodies that cause a fertility problem, we should have already started seeing some of these problems materialize by now.  No greatly increased reports of fertility problems since the widespread proliferation of Covid-19 have, however, been forthcoming.
4. Covid-19 isn't the only virus that has a spike protein.  Many common colds / flus are caused by coronaviruses that have very similar spike proteins.  Presumably, these virus spike proteins *also* are similar to syncytin-1, and yet there have been no indications over the years that people who have suffered from a coronavirus of one sort or another have had any sort of fertility problems more than other people.

Therefore, it is extremely unlikely that the new vaccines cause any sort of fertility problem.

How Various Vaccines Work--Simplified

I was asked recently about whether the new vaccines could cause some unexpected trouble because they "modify our DNA", as opposed to previous vaccines.  To "modify our DNA" certain *sounds* kind of risky, I agree.  There was also some concern about these vaccines being able to damage the reproductive system and cause infertility.

The short answer is that this isn't a concern, but as I gave the answer, I realized there might be some important misconceptions behind this concern that could be cleared up by a longer answer.  So I'm going to give a very simplified (and therefore necessarily incorrect) explanation of some basic biology and how it relates to viruses and vaccines.

I'm going to follow this up immediately with an evaluation of the inherent risks of some of these different vaccine types and address the infertility question.

DNA, mRNA, and Proteins

DNA

Everyone knows that DNA is in some way the "master plan" for the whole body: it's the set of instructions that makes each person unique.  And I think it is a partial understanding of this that makes people very nervous when they hear about something that messes with their DNA.  I think they imagine their DNA as some single master plan that controls their entire body, and therefore anything that messes with their DNA has the potential to mess up literally anything about their body.

But there is no single "master" copy of DNA--that's not how it works.  Your DNA is replicated billions of time in cells all throughout your body.  There is nothing that can change your DNA throughout your whole body; it only exists one cell at a time and if you want to change it you have to change it one cell at a time.

Furthermore, aside from the very beginning of life when you exist as a very small set of cells, there's never actually just one version of your DNA.  DNA mutations happen all the time at the time of cell replication.  A mutation is usually just an error in cell replication--an incorrect copy.  And since these happen all the time, it's certain that you have many slightly different versions of your DNA in different cells all throughout your body.

The cellular replication process does have several error correction procedures it goes through.  For serious problems, badly messed up DNA or malformed cells are destroyed.  *Slightly* modified DNA can get through this all the time though.  Cancer exists in the grey area of this process, being mutated sufficiently enough to cause problems but *not* enough to be attacked and disposed of by the body's natural mutation clean-up system.

The bottom line is, something altering your DNA isn't the equivalent of mutating you into a different creature.  It's something that happens on the level of individual cells and the impact depends on how successfully the new cells replicate and how successful the body's immune system is at disposing of these mutations.

DNA, mRNA, and the production of proteins

Let's do a quick review on how the microscopic structures of the body are built from DNA.

Imagine DNA as a large book written in Braille.  It contains instructions for all the different things that the body builds at a microscopic level: the proteins.  It sits in the center of the cell.  When a new structure needs to be built, a piece of Play-Doh comes along and presses against the paragraph that has the instructions for this structure.  It then goes over to the cellular protein factory, which reads the impression and creates the protein by a reverse impression process.  This bit of "Play-Doh" is the "messenger RNA" or "mRNA", so called because it takes the production order "message" from the DNA to the protein factory.

How viruses hijack this process

Viruses survive by invading and hijacking this process.  To be successful, a virus needs to do the following:

1. Spread: survive outside the body for a bit of time
2. Penetrate: get into the body and survive there among the cells but not in them for a while
3. Infiltrate: gain access to the inside of reproducing cells
4. Replicate: Use the cell's own replication ability to replicate themselves, using one of various strategies:
1. Some viruses have their own DNA replication abilities; they just need to get into the protein factory in order to hijack the facilities to duplicate themselves using their own DNA.
2. Some viruses modify the DNA in the cell.  They stick their own instructions into the DNA "book" in a place where the cell will read with the mRNA.  The mRNA then takes the virus instructions to the protein factory and the factory produces more virus instead of the normal things it would instead.  NOTE: in this case, the modified DNA is not replicated.  It's just been modified so that the *virus* will be replicated.
3. Some viruses just produce their own mRNA and arrange so that their mRNA gets sent to the protein factory instead of the normal mRNA.  The end effect is basically exactly the same as modifying the original DNA; it just skips a step.
5. After replication, each copy starts over again at step 2.

How the immune system defeats viruses

This is really complicated, but to overly-simplify (and skip a bunch of steps), the body determines that there is a foreign invader and starts working on developing new proteins that are custom-shaped to latch on to the foreign particles and somehow neutralize them ("neutralizing antibodies").

In the case of Covid (and other coronaviruses, actually), it seems that the primary thing that the body's immune system attacks is called the "spike protein".  This is the spiky protrusion around the outside of the virus, and it is used by the virus for step 3 ("Infiltrate")--it works kind of like a skeleton key to break into the cell.  The neutralizing antibodies that the body produces bind to the spike protein, so that it no longer fits into the key hole.  The virus particles are thus not able to enter cells and not able to reproduce.

How vaccines also cause the immune system to produce neutralizing antibodies

The goal of a vaccine is to trigger the same immune response that the real virus does, but without the virus actually replicating throughout the body, causing the disease.  There are several strategies that have worked for this:

1. Infect the person with a disease that is really similar to the original disease, but much less severe.  The smallpox vaccine was like this; cowpox is a disease that works much like smallpox, so that the antibodies that the immune system produces to counteract it happen to also work against smallpox.
2. Take a virus and somehow neuter it so that its ability to replicate is destroyed.  I believe the MMR vaccines work in this way; I think they use UV radiation to damage the virus.  Then they inject you with a quantity of the virus.  The virus particles retain the protein structures necessary to invade cells (I think) and the immune system generates neutralizing antibodies to those structures.  There is a risk in this method that the culture is not completely neutralized and enough viable virus is left to replicate and cause the disease you are trying to vaccinate against.  (It's a low risk; about 1 in 1 million).
3. There are new kinds of vaccines that try to be much more targeted in how they operate.  Rather than using a full virus (either a weak relation or a weakened form) for the body's immune system to react to, these vaccines get cells to produce just small parts of a virus.  There are two main new technologies being employed to do this, which I will now describe.

The newer vaccines

Adenovirus vector vaccines

Adenovirus vector vaccines are essentially genetically modified cold viruses.  They still operate like normal viruses up until they invade your cells.  After this, when it comes time for them to inject their genetic replication DNA into the cell, this genetic replication code has been replaced with a specified set of instruction instead.  So the messages that get sent to the protein factory aren't "build another copy of this virus", but rather just "built this specific structure" instead.  In the case of a coronavirus vaccine, the specific protein that they cause to be produced is the spike protein.  The infected cell therefore generates that spike protein, which the body's immune system recognizes as foreign material.  The immune system therefore generates antibodies to the spike protein of a virus without ever having had exposure to the whole virus.

Since an adenovirus vaccine does not have replicating code, it will not replicate throughout the body.  The modified virus will infiltrate those cells with which it comes into contact at the site of the injection, those cells will operate differently for a time, and those cells will then be destroyed and disposed of by the body's immune and waste disposal systems.

mRNA vaccines

mRNA vaccines aim for the same effect as the adenovirus vector vaccines, but with an even simpler delivery method.  With these vaccines, we just straight up manufacture the messenger RNA fragments that will tell the protein factory to produce the spike protein.  Our chemical gene manufacturing processes have gotten good enough where we can mass produce small segments of RNA--so that's what we do.  We then encapsulate bundles of these mRNA fragments into lipid nanoparticles so that they can survive for a while inside the body.  ("Lipid nanoparticles" sounds exotic, but it is less so than you might think.  It's actually not dissimilar to the process of making mayonnaise, it's just a much finer emulsion.) When these are injected into someone, a lot of them bump into cells and get absorbed into them.  The mRNA fragments then get into the cell protein factory, causing those cells to start producing some spike proteins, thus triggering the immune response.

As with the adenovirus vector vaccines, there is no replication code injected, so the vaccine can only cause a set number of cells to produce spike proteins.  Again, these cells will be disposed of by normal waste disposal processes.

Risk Analysis of Moderna and Pfizer Vaccines: Update

Since I first published my vaccine risk analysis, one person (the first) has died shortly after receiving the vaccine and possibly because of the vaccine: click here for an article on Dr. Gregory Michael.

I think it's worthwhile to take a look at this and see if this affects the bottom-line risk analysis.

Did Dr. Michael die because of the vaccine?

Bottom line: not certain, but quite possibly.

In more detail:

Dr. Michael developed a condition 3 days after having been vaccinated called "acute immune thrombocytopenia" (ITP), which happens when your immune system begins attacking your own blood platelets.  In about 5% of adult cases, this can lead to death by hemorrhaging, which is what happened to Dr. Michael.

Since vaccines work by triggering the body's immune system, I had already identified immune system overreactions as the most likely cause of adverse side effects from the new vaccine.  It is therefore quite plausible that the vaccine was the cause of, or at least the trigger for, the condition that lead to Dr. Michael's death.

However, we also cannot rule out tragic coincidence at this time.  As of today's date (January 14th), about 11 million doses of the new vaccines have been administered in the U.S. alone.  ITP is rare, but it occurs in about 2 adults per 100,000 each year.  This means that if you picked 11 million adults at random in the U.S. and did nothing to them for one month, you would expect about 18 of them to develop ITP just by chance, and given a 5% fatality rate, one of those 18 or so would be likely to die.  One death from ITP out of 11 million doses in one month therefore is not above the level where it could be an unfortunate coincidence.

However, I feel that it is somewhat more likely than not that the vaccine triggered the condition in Dr. Michael in this case.  ITP is normally triggered by something that activates the immune system: either a pathogen or a medicine such as a vaccine which triggers the immune system.  In Dr. Michael's case, the only such cause we know of is the vaccine; he wasn't otherwise sick, nor had he taken another medicine that could have triggered the condition (that I could tell by the report, anyway).  So I think it is reasonable to suspect that the vaccine had a part in causing his death, even if we can't rule out coincidence and an unknown other cause.

Was Dr. Michael susceptible to ITP even aside from the vaccine?

Probably, yes.  In my risk analysis, I emphasized that many of the mechanisms by which the vaccine might cause serious side effects in its recipient are also possible as side effects of the virus itself.  It stands to reason that if the side effect (ITP in this case) is caused by an immune reaction to the vaccine and if the whole point is for the vaccine to trigger the same immune reaction that the virus would, then that side effect of the vaccine would also be a side effect of the virus.

This does turn out to be the case with ITP.  Although not listed in my short-list of known serious side effects of Covid-19, it turns out that ITP has already been identified as one of the myriad possible symptoms and syndromes that can be triggered or caused by Covid: see this article here.  We don't know the specific reasons why some people can be susceptible to ITP and other people aren't, but genetics are vaguely suspected.  It is therefore more likely than not that Dr. Michael was in some danger of developing ITP from catching Covid, as well as from taking the vaccine.  This is, however, impossible to know for sure at this point.

Should I update the risk analysis bottom line because of this occurrence?

No, that isn't necessary.  Previously, I had set the risk of death from getting both doses of the vaccine at a maximum of 1 in 1 million, which was based on 2 million doses administered at the time with no deaths.  We now have 11 million doses administered and 1 known death.  If we attribute this death completely to the vaccine, that means I should adjust the chances of dying from the vaccine down to 1 in 6.5 million.

However, as I purposefully decided to under-rate the risks of the vaccine and over-rate the risks of the virus and data is still relatively sparse, I will keep the risk at 1 in 1 million for now.

Asymmetrical Processing of Ideas: Part 1

In connection with theories that the recent presidential election was fraudulent (with which I strongly disagree), I've had some discussions recently about how people can become very mistaken about reality, holding theories as certainties when the actual evidence for those theories are very thin.  Someone commented that they wondered whether people who do this were just unaware of the concepts of burden of proof or Ockham's Razor (aka the "principle of parsimony").

I disagreed, for the reason that I believe you can usually see a perfectly good understanding of those principles in operation when the person is critiquing someone else's theories.

The problem is therefore not a lack of understanding of correct intellectual procedures, but a radical asymmetry in the application of those procedures. Theories that fit into a certain a priori favored worldview are subjected to token scrutiny only, while anything that challenges that worldview is subjected to skepticism of the most stringent kind. I think there are several common manifestations of this:

1. A too-complete rejection of arguments coming from entire classes of people because they are of the opposition. "Wait, you're seriously quoting something from the Washington Post? LOL! Don't you know you can't trust anything they say?" Or, "I only need to see somebody quote from Matt Walsh to know I can safely ignore anything they ever say again."
2. The complement to this: an extreme generosity in forgiving the failures of someone or some set of ideas because they pushed some idea or goal that is very important to you. "Fr. So-and-so is accused of sexual molestation?? But he's a conservative priest who loves Latin . . . this must be a setup." Or, "OK, so yeah, some people have taken this ideology to an extreme and it resulted in socialist hell-holes of a country. But this is *so* much more generous to the poor, there must be some good in it we can keep!"
3. Excessive focusing on one aspect of a theory you like that you know to be true, while ignoring crucial parts that are way less certain. "The media is absolutely biased against conservatives, and they hate Trump with a passion. This would need to be the case for a widespread conspiracy to defraud Trump of the election to be successful. Therefore, it's reasonable to believe that this is absolutely happening!" Or, "The actions of this policeman against this black man is an obvious, complete outrage. It's reasonable to believe that the police in general are a complete hotbed of racism and hatred!" Emotionally, you can take certainty in one thing and spread it out to a lot of related things, without a rational justification.
4. The complement to the above, finding one aspect of your opponent's argument that you know with certainty is false and focusing excessively on it, but without questioning how badly this error damages the overall argument. Not all flaws in an argument are fatal, but to someone determined to reject an argument, oftentimes any flaw is sufficient reason to throw away the whole thing in disgust.
5. Radical disengagement from people or activities that could give you sources of information that support your opponent's argument over yours. The time someone is willing to spend listening to his opponent, or looking for evidence that will support his opponent, is a fantastic indication of how objective he is willing to be overall. For the social media conspiracist, the amount of time he is willing to spend reading lengthy, often repetitive treatises from his favorite internet talking heads is usually vastly greater than the time he is willing to spend reading opposing viewpoints.

I would like to look at examples of all of these types of thinking in the current social media debate over the Capitol Building riot.  Since I am in the camp of "Trump deserves to be impeached for what he instigated" and "the violence of this riot was primarily coming from extremists who have been part of the Trump movement, not primarily from leftist plants", I am going to try to make more of an effort to find examples of this type of asymmetric thinking from proponents of these viewpoints.  However, I will be looking at this from both sides as well.