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Basic Theory of Vaccines for Dummies

Enlightening Comments and Discourse of Reason on article “Toward Understanding of Vaccines”

1. Discourse of Reason

The problem of vaccines understanding is essentially trivial. But it is also an over two-century-old formal logic fallacy, so it is very complex as well. Furthermore, comments>> from academic officials interpreting my work as “analysis of AIDS campaign” formally look as if they do not understand what the talk is about (of course, I think it was an intentional misinterpretation of my work). Therefore, here is my desperate attempt to write shortest and simplest popular discourse on this problem to help understand the problem of understanding vaccines.

Let’s draw an allegorical parallel between vaccines and understanding the process of making wine which is traditionally also often considered to be “more of an art than a science”. For many thousand years it is known that grapes may be converted into wine by numerous methods of special growing, crashing, cooling, warming, settling, aging etc… Similarly, since Pasteur time we know that deadly virus may be converted into vaccine by some magic tricks of special growing, passing, aging, warming, exposure to oxygen etc…
It is a “great art” or an “empirical understanding” of wine and vaccines.

Now let’s say that “wine is a modified (or enhanced, or enriched) grape juice”. Can it be accepted as scientific explanation of wine? Nope it is useless and it is meaningless.

It is not the case with vaccines. The statement that “vaccine is modified (or weakened, or attenuated) virus“ does have sense. If wine had been given to us by gods or extracted as mineral from wine-mines – there would be a controversy whether wine is modified grape juice or is it some other staff, rancid Coca-Cola for instance. This question would be ultimately answered when people learn to make wine with their own hands.

And that is exactly what Louis Pasteur did. First vaccine (against smallpox) was a naturally existing cattle disease - cowpox. Its protective effect against smallpox was discovered in 1796 by Jenner and there was indeed a fierce theoretical debate – mainstream doctrine was that cowpox is a modified smallpox which is essentially the same disease (actually, doctrine also erroneously included horse grease as third modification of smallpox). "Anti-vaccine" scientists maintained that relationships between cowpox,horse grease and smallpox are perfectly unknown, so they may say for example that cowpox looks more like syphilis (large pox).

In 1880 Pasteur found a method of preparing vaccine against fowl cholera by growing it in vitro for extended period of time. He claimed that now he knew for sure that this vaccine is an “attenuated” cholera so his vaccine was more scientific than cowpox. It was an anti-vaccine claim and though Pasteur made wise curtsey that he does not wish to make assertions about cowpox-smallpox relationship, he got lot of troubles with that work and even challenged to a duel after debating it in French academy.

Pasteur's invention of word “attenuation” was not assumed to be an ultimate universal understanding of vaccines. Word "attenuation" is not suitable for description smallpox vaccine which is more virulent than smallpox (shorter incubation period, large poxes instead of small ones, vaccination does not protect from cowpox). That is, cowpox looks more like "enhanced" rather than weakened or attenuated form of smallpox. Similarly, most glamorous Pasteur's vaccine against rabies should be attenuated from “fixed” laboratory strain of rabies virus, which is also more virulent than street rabies. Original 1880 Pasteur's fowl cholera article is quite readable – look here >>. It is easy to see that Pasteur did not pretend that he knows clearly what his new grand word “attenuation” actually means.

Now the most tricky part - explanation what sort of theory I'm talking about.
Parallel with wine works again presenting "full package" of theories available for every aspect of science of alcohol.
- First, we should know how wine works in human organism. It's a big science called "neuropharmacology of alcohol" studying how ethanol disrupts functioning of nerve receptors. Not too practical - I'm afraid it is not very helpful for developing better wine. Everything is fine with this aspect in vaccine science - it is all about antibodies, T-cells etc...
- Then, we need to know what happens with grape juice when it transmutates into wine. It's all about yeasts, fermantation - also a big science, surely more practical. For vaccines it is talks about attenuation described above. An obvious gap but this is not primary source of trouble.
- The talk is about the "basic scientific explanation" or "fundamental understanding" of what is wine and what is vaccine.
Most important from practical point of view, we need to know that ethanol is the factor defining effectiveness of wine and fusel oils are responsible for hangover as side effect. As a result of such understanding we have got the great scientific method of distillation giving us opportunity to get drunk quickly and with minimal headache. (yes, this is not quite correct account of science of alcohol) It is not mathematically rigorous theorem but just a common sense default hypothesis that there are usually two different factors in such things like alcohol or vaccines: one responsible for efficacy and another for safety. These are two different things that usually should be explained by two different explanations.
Alas, classical Pasteur's definition of vaccine as attenuated virus implies that all you need to make vaccine is to remove its pathogenicity, that is to make it safe. There was no slightest idea what is needed to make vaccine effective. This problem was lost in suppressed discussion on cowpox-smallpox relationship: smallpox inoculation was widely used as protection against smallpox before Jenner. So smallpox may be considered as worse vaccine and cowpox as better vaccine - it is the exactly the same problem of understanding vaccines efficiacy.
If vaccine happens to be ineffective, you should try another strain of virus or find another method of attenuation hoping that some day it will accidentally help.

Official views of modern science upon understanding factors defining vaccines efficacy are very difficult to describe. In my interpretation, it is something like that vaccines efficacy is some magic property defined mostly by favor of gods, which may be slightly improved by proper adjuvants, vaccination schedule etc. e.g. from Wikipedia: "The efficacy or performance of the vaccine is dependent ... on the disease itself (for some diseases vaccination performs better than for other diseases)"IMHO this rhetoric figure means something like that "we do not know why for some diseases vaccination performs better than for others", also hinting that "we should not know" or "we can not know".

Great gurus address this problem with even more vague phrases, e.g. "Salk believes that one of the main scientific obstacles is that many scientists r&d vaccines "don't have a clue" what's required to make an effective vaccine ... It's chaos... There is going to be a need for more awareness not of the pathogen, but of the host - says Salk" (Science, 265, 1371 (1994))

I have just an alternative suggestion that there is quite definite physical property defining efficacy of vaccine. My guess is that it is antigenic diversity of vaccine.
It's simple: For example there are more than hundred antigenic variants of common cold (rhyno)virus. So that we may get colds twice a year throughout whole life - every time with a different form of virus. The suggestion is that vaccine “attenuated” from single antigenic form of rhynovirus does not protect at all. Vaccine containing 10-20 most frequent antigenic forms is a bad vaccine which may show some protective effect in a statistical study. And at last vaccine containing almost complete repertoire of antigenic forms should be the real effective vaccine.

Here is why I like my suggestion better than official views:
1. Existence of universal factor defining immunizing power of vaccine is a common sense hypothesis.
2. It explains methods of deriving and characteristics of classical vaccines (in particular rabies and smallpox)
3. It explains why modern “high-tech” vaccines have MUCH lower efficacy than old empirical live vaccines.

Naturally, telling such God's Truth about vaccines was impossible without firm belief that vaccinology is governed by technical idiots. There is nothing unusual, it seems to be a typical scenario of degradation of once successful fields of techonologies. Let's call it "post-breakthrough syndrome" - after great advances there is little point to continue working, it is more reasonable to divert efforts to selling available achievments. My favorite story about a similar trounle in NASA - Richard Feynman's report on Space Shuttle Challenger Accident here>> (actually, article in Sci.American August 1986 is what did impress me at that time ).
Not sure about words - "technical idiocy" seems to be quite politically correct term for estimating probability of space shuttle failure at 1/100,000. Perhaps "folly which should be obvious even to a child" may look better.

I have written several notes reporting several other "technical idiocies" in vaccinology: