Thread by @akoz33

Most of us have, to a greater or lesser extent, have had to learn during this epidemic some molecular biology and even it’s subset, microbiology. In my own case, in addition to Twitter I have a daughter who has a doctorate in molecular biology from embl.org/sites/heidelbe… and

who works as a scientist for one of America’s best known biotech companies (which, however, does not make vaccines or create dangerous chimeric viruses) so she would often tell me a lot about DNA, RNA, gene editing etc, but it all seemed too lacking in overall unity & especially

mathematical structures to stay in my head for long. So only once this covid thing started I began to acquaint (or reacquaint) myself with the basic concepts of the subject. And it seems to me now that, while it’s an enormously rich subject, which had made huge advances, it still

give the impression of being in its infancy, at least when you compare it with a mature science like particle physics (it’s much closer to the situation in something like climate). In other words, there is a huge and impressive body of theory, on which there is a general

agreement, and there are some impressive practical applications in medicine (mRNA vaccines, for example) but when it comes to almost any of these applications, there is enormously wide disagreement between “experts”, so much that what one very credentialed expert (even a Nobel

prize winner) says will often be regarded as totally unfounded or even almost insane by another (so things happen very rarely in physics and, of course, even more rarely in maths, where “insane” usually has to be literal, but of course math is not an empirical science). Also, I

have to say, that although biological models if, say, the immune system, are subtle and impressive, when it comes to actual “medical practice” one finds that people often rely on their own “pet theories”, for which there is no solid basis, and when it comes to getting evidence,

there are just fairly primitive mathematical models and statistical techniques (“curve fitting”), which rarely can be very compelling (in other words, it’s definitely not physics).
A typical example that I have recently been thinking about: Inhave listened to microbiologists

arguing that our long isolation from microorganisms (through social distancing and masks) will make us more vulnerable to them when it ends. As the result we should expect more severe outbreaks of flu etc. According to one well known microbiologist, our immune system needs to be

in constant tension with microbes and when this is lacking it grows weaker, just like a muscle that is not used or exercised. But others say that this is nonsense and there is no evidence of any such thing.
When one tries to think in more detail about how this kind of thing

could actually come about, there seems to be little one can say for sure. Certainly, the immune system of children is only developing and they need contact with viruses and bacteria to develop antibodies and memory cells (these belong to the adaptive immune system). So children

may indeed find themselves having missed something that they need, although it’s not clear why a postponement of infections should make them worse. For grown ups, it’s difficult to see how getting actually infected maybe of any benefit at all - I’d say that superficially at

not having had a cold or a flu for almost two years should make us stronger. As far as I can make out, the so called “innate immune” system, which in a healthy person is often able to destroy pathogens before antibodies are made, is more mysterious. It involves such things as

interferons and natural killer cells. Now, there is a lot of evidence, that the innate immune system can be “trained” (see for example nature.com/articles/s4157… ). There is a growing body of evidence that vaccines involving a live virus, such as BCG and OPV have a strong effect on

innate immunity, they train the system so that it is able to respond much more effectively not just against the viruses they wired meant against but against all pathogens. Studies in many countries have shown quite convincing,y that people who received these vaccines tended to

suffer less from disease (including cancer) and tend to live longer. However, this does not seem to be true of vaccines using a dead virus.
Is it true of the current covid-vaccines? I have no idea and have not seen or heard anyone write or talk about this. The vector vaccines

(AstraZeneca, J&J and Sputnik) contain a live (though disabled) adenovirus - it would seem then that they should provide some of the well documented benefits of OPV (Soviet studies have shown OPV to be more effective against flue, purely through its effect on the innate immune

system) than specific flu vaccines. If the adenovirus vaccines have anything like this effect (I have no idea about the mRNA ones) we should be perhaps better defended against flu than we would have been after a flu season.