This is not an easy blog to write.  Doctors Novella and Gorski want the entries to be formal, academic, referenced, with a minimum of snark.

For the most part I comply. But sometimes. Sometimes. It is hard, so hard,  not to spiral into sarcastic diatribes over the writings that pass for information on the interwebs. How should one respond to profound ignorance and misinformation?  I wish, sometimes, that I could be an irascible computer as well.

What brings on this particular bit of angst is a bit of whimsy on the Internet called “9 Questions That Stump Every Pro-Vaccine Advocate and Their Claims.”  by David Mihalovic, ND. Mr. Mihalovic identifies himself as “a naturopathic medical doctor who specializes in vaccine research.” However, just where the research is published is uncertain as his name yields no publications on Pubmed.  BTW. I specialize in  beer research.  Same credentials.

The nine questions show up frequently on the interwebs, similar to questions on what to ask when you want to stump an evolutionist.  Similar to the supposed stumpers for evolution, the vaccine questions are grounded in misinformation, ignorance or laziness.  Let’s go through them one at a time.

1. Could you please provide one double-blind, placebo-controlled study that can prove the safety and effectiveness of vaccines?

One trial? It took me 55 seconds to find  ”Efficacy of 23-valent pneumococcal vaccine in preventing pneumonia and improving survival in nursing home residents: double blind, randomised and placebo controlled trial” and that included time to boot the browser and mis-spell the search terms.  ’Vaccine’, ‘efficacy’,  ’randomized’ and  ’placebo control trial’  results in 416 Pubmed references; add ’safety’ to the search terms, you get 126 returns. 416 is easily more than one.  Of course, to find them you have to look.

Of course, I am a highly educated adult who constantly searches the web for medical information.  For hoots and giggles, I asked my 12 year old son, whose passions are basketball and filming comedy videos, to find me a reference that met the same criteria and I timed him.

Twenty two seconds, not including boot time,  to find “Randomized, Placebo-Controlled Trial of Inactivated Poliovirus Vaccine in Cuba” from the NEJM.  Can anyone beat my son?

12 yo one,  Mihalovic 0.  Served.

As long as we are on the topic, since he evidently place great store in science, could Mihalovic please provide one double-blind, placebo-controlled study that can prove the safety and effectiveness of naturopathy?  I would be happy at this point to know just to know he was able to do a pubmed search correctly just to make me look the fool.

2. Could you please provide scientific evidence on ANY study which can confirm the long-term safety and effectiveness of vaccines?

Long term is vague. What is long term?  Smallpox disappeared in 1977  thanks to the vaccine.  I have not seem a case of smallpox in my medical career, which now on it’s 31st year. No reported long term toxicities of the smallpox vaccine  and the eradication of smallpox appears to me to represent reasonable evidence for long term safety and effectiveness. But it would.

No vaccine has 100%  efficacy, and whether  infected naturally or by  a vaccine, immunity wanes with time.  In  earlier times, people would have their immunity boosted by exposure to disease and maintain their antibody levels.  It is not the initial infection that leads to better immunity from natural infections, as posited by some antivaccine people, but the the fact that people were constantly re-exposed to wild type disease.

It is interesting what is  occurring with shingles.  Everyone used to get chickenpox as a child, and then, as they raised their kids and grand kids, were re-exposed to the virus and boosted their immunity. Currently, due to the chickenpox vaccine and a change in the  way children are raised, older adults are not getting exposed naturally to chickenpox, immunity is waning, and there is an increase in shingles in older adults.  Part of why they need the zoster vaccine.

Clever conspiracy to increase the use of the zoster vaccine, huh?

Unless exposed to new infection, immunity, as measured by antibody levels directed against the infecting agent, can decline over time. That is to be expected.  The nice thing about the immune system, unlike water, is that it remembers the infection. It is primed so that if exposed again at a later date, it can almost instantly produce large amounts of antibody to nip an infection in the bud. So rather than prevent infection, in some people far removed in time from the vaccine, they may instead have a shorter, less severe illness and be infectious for a shorter period of time, thereby decreasing spread.

There is a nice review in the NEJM on duration of immunity (first search in Pubmed using duration of immunity vaccine, results in 17 seconds, including correcting typos.  Seriously, just how hard is it to find this information?  As would be expected, it depends on the disease and the vaccine (live better than killed). They estimated the half-life for the varicella zoster virus immunity at 50 years, 200 years for measles and mumps, and 11 years for tetanus.  If you peruse the references, you can find other studies that show variable but sustained response to vaccines,  for example 90% maintain immunity to smallpox up to 75 years after vaccination.

Long term safety was more difficult, 5 years was the limit of time I could find  for safety studies of  Hepatits B.  Most vaccine toxicities are found in the first week or two after the inoculation and the studies follow most patients for a year.  Probably would not cut it as long term for Mihalovic.

BTW, could you please provide scientific evidence on ANY study which can confirm the long-term safety and effectiveness of naturopathy?

3.  Could you please provide scientific evidence which can prove that disease reduction in any part of the world, at any point in history was attributable to inoculation of populations?

Smallpox? Smallpox? Smallpox? Anyone? Smallpox? Buehler? Buehler?

Again I get back to the whole binary, black and white approach that characterizes many with whom we cross medical swords.  The decrease in infectious diseases has been multifactorial, due to improved nutrition, improved hygienic (lets hear it for the flush toilet) and understanding the epidemiology of diseases.  Knowing how a disease is spread has always been critical in decreasing its spread.  Note that none, none, none of the interventions that have decreased the spread of infections in the last 200 years or so have come from naturopathic tradition.

The teasing out the effects of vaccines on populations is always fraught with potential controversy. There are always multiple confounders.  The best example of the beneficial effects of vaccines was from JAMA.

“Objective  To compare morbidity and mortality before and after widespread implementation of national vaccine recommendations for 13 vaccine-preventable diseases for which recommendations were in place prior to 2005.

Design, Setting, and Participants  For the United States, prevaccine baselines were assessed based on representative historical data from primary sources and were compared to the most recent morbidity (2006) and mortality (2004) data for diphtheria, pertussis, tetanus, poliomyelitis, measles, mumps, rubella (including congenital rubella syndrome), invasive Haemophilus influenzae type b (Hib), acute hepatitis B, hepatitis A, varicella, Streptococcus pneumoniae, and smallpox.

Main Outcome Measures  Number of cases, deaths, and hospitalizations for 13 vaccine-preventable diseases. Estimates of the percent reductions from baseline to recent were made without adjustment for factors that could affect vaccine-preventable disease morbidity, mortality, or reporting.

Results  A greater than 92% decline in cases and a 99% or greater decline in deaths due to diseases prevented by vaccines recommended before 1980 were shown for diphtheria, mumps, pertussis, and tetanus. Endemic transmission of poliovirus and measles and rubella viruses has been eliminated in the United States; smallpox has been eradicated worldwide. Declines were 80% or greater for cases and deaths of most vaccine-preventable diseases targeted since 1980 including hepatitis A, acute hepatitis B, Hib, and varicella. Declines in cases and deaths of invasive S pneumoniae were 34% and 25%, respectively.”

Milhalovic,  could you please provide scientific evidence which can prove that disease reduction in any part of the world, at any point in history was attributable to naturopathy?

4. Could you please explain how the safety and mechanism of vaccines in the human body are scientifically proven if their pharmacokinetics (the study of bodily absorption, distribution, metabolism and excretion of ingredients) are never examined or analyzed in any vaccine study?

There is, superficially, some truth in this statement.  Most pharmacokinetics are done prior to the clinical efficacy trials.  That is why there are phase 1 and phase 2 trials. The assumption being that if you exam influenza vaccine pharmacokinetic studies in one group it can be extrapolated to similar populations.  I think that is reasonable. So no, there are no pharmacokinetic studies in the clinical efficacy trials, those were done prior to the efficacy trials.  But it is not hard to find the phase 1 and 2 trials if you are so moved.

Milhalovic, could you please explain how the safety and mechanism of naturopathic nostrums in the human body are scientifically proven if their pharmacokinetics (the study of bodily absorption, distribution, metabolism and excretion of ingredients) are never examined or analyzed in any naturopathic nostrum study?

Is this getting old?  There is something to be said for repetition.

5. Could you please provide scientific justification as to how injecting a human being with a confirmed neurotoxin is beneficial to human health and prevents disease?

I presume the issue is mercury. Maybe aluminum. The latter is not in most vaccines, although as been discussed at length on this blog, the amount of mercury and aluminum found in vaccines is minimal and, at the dosing and formulation, has never been demonstrated to cause neurotoxicity from vaccines.  Of course, I am old school and think there is a dose response effect of drugs, and that a greater amount leads to a greater response.  Most naturopaths receive extensive training in homeopathy, where the less the amount, the greater the response.  So I would presume arguments based on chemistry would have little meaning to an ND, although I would not want my appletini made by a practitioner of homeopathy.

Of course, it is not the ‘neurotoxin’ that is being used to prevent disease, but the antigens of the potential infection. That is assuming that the author of the nine questions does not consider the antigens to be neurotoxins, and to judge from his understanding of disease later in the post, I am not so certain he warrants the benefit of the doubt.

Could you please provide scientific justification as to how applying naturopathy to a human being is beneficial to human health and prevents disease?

6. Can you provide a risk/benefit profile on how the benefits of injecting a known neurotoxin exceeds its risks to human health for the intended goal of preventing disease?

Since there is no longer mercury in most vaccines, I will assume, for the sake of argument, he is referring to aluminum.  Risk from aluminum in the H. influenza type b vaccine, where aluminium is used as a adjuvant: zero.

The benefit from the vaccine:

“From eight trials, the protective efficacy of the Hib conjugate vaccine was 84% (OR 0.16; 95%CI 0.08-0.30) against invasive Hib disease, 75% (OR 0.25; 95%CI 0.08-0.84) against meningitis, and 69% (OR 0.31; 95%CI 0.10-0.97) against pneumonia. Serious adverse events were rare.”

Seems a good trade off. No risk from aluminum, significant decrease in morbidity and mortality from disease.

7. Could you please provide scientific justification on how bypassing the respiratory tract (or mucous membrane) is advantageous and how directly injecting viruses into the bloodstream enhances immune functioning and prevents future infections?

Well, things really get off the rails here.  Vaccines are not injected into the blood stream, they are infected into the soft tissues.   At a simple level, an infection enters to body, the body makes a variety of antibodies to the constituent parts of the infecting organism and next time the patient is exposed, the pre-existing antibody can, if there is a match with new strain, inactivate the new infection.

It doesn’t matter how the antigen is presented to the immune system, the response is the same. Natural influenza, inhaled influenza vaccine, or injected influenza vaccine, the same antibody will be made to the proteins.

Mihalovic says later

“All promoters of vaccination fail to realize that the respiratory tract of humans (actually all mammals) contains antibodies which initiates natural immune responses within the respiratory tract mucosa. Bypassing this mucosal aspect of the immune system by directly injecting viruses into the bloodstream leads to a corruption in the immune system itself. As a result, the pathogenic viruses or bacteria cannot be eliminated by the immune system and remain in the body, where they will further grow and/or mutate as the individual is exposed to ever more antigens and toxins in the environment which continue to assault the immune system.”

This is what we call in the trade, gibberish. At least it makes no sense to me.  I will leave to the readers to search, Bible Code style, for truthiness in the above selection.

8. Could you please provide scientific justification on how a vaccine would prevent viruses from mutating?

That is actually a very interesting question. It has nothing to do with why we give vaccines and  I fear our intrepid ND does not have a firm grasp on what he is talking about as he says

“Despite the injection of any type of vaccine, viruses continue circulating through the body, mutating and transforming into other organisms. The ability of a vaccine manufacturer to target the exact viral strain without knowing its mutagenic properties is equivalent to shooting a gun at a fixed target that has already been moved from its location. You would be shooting at what was, not what is!”

Mutating and transforming into other organisms. Sigh.  Either the author is a sloppy writer  (sloppy writing (not typos, but logic and word selection) reflects a sloppy mind) or his understanding of microbiology is so profoundly mistaken it boggles the mind that he takes care of patients.  And in Oregon he would allowed by the state to prescribe antibiotics and other pharmaceuticals.

If you have a population of viruses and a specific antibody against the virus, then those naturally occurring mutants that are not recognized by the antibody should have a replication advantage.  It is possible that the vaccine can help select for new strains of an infection, but not new organisms.

Vaccines selecting for new mutants has been looked at for the Hepatitis B vaccine, and found not to be a issue.

In HIV, there is an ongoing interaction between the immune response and the virus, driving mutations that escape the immune system and, in some patients leads to a marked increase in HIV replication and a clinical decline decline. Oh wait, this is a natural infection. That shouldn’t happen.  It is the vaccines that do this.

There is nothing unique about the vaccine response acting as environmental pressure on the evolution of infections; the response from the natural infections should be the same.  I would wonder, since the response to  a natural infection is broader, with antibodies made to numerous parts of the infection, rather than the few key antibodies provided by the response to the vaccine, whether a natural infection would lead to a faster mutation rate.  As a rule in the microbial world, the more intense the stress, the faster and more varied the mutations.  More antibiotics leads to faster development of resistance in E. coli, not its delay.

9. Could you please provide scientific justification as to how a vaccination can target a virus in an infected individual who does not have the exact viral configuration or strain the vaccine was developed for?

Mr. Black and White.  Antibody response is not all or nothing, there is a gradient of response between the developed antibody and the site to which it is directed.  A good example is the H1N1 influenza.  People exposed to the strains from the first half of the century had antibody that was partially protective for the 2009 strain.  The reason?

“The pandemic influenza virus (2009 H1N1) was recently introduced into the human population. The hemagglutinin (HA) gene of 2009 H1N1 is derived from “classical swine H1N1″ virus, which likely shares a common ancestor with the human H1N1 virus that caused the pandemic in 1918, whose descendant viruses are still circulating in the human population with highly altered antigenicity of HA. However, information on the structural basis to compare the HA antigenicity among 2009 H1N1, the 1918 pandemic, and seasonal human H1N1 viruses has been lacking. By homology modeling of the HA structure, here we show that HAs of 2009 H1N1 and the 1918 pandemic virus share a significant number of amino acid residues in known antigenic sites, suggesting the existence of common epitopes for neutralizing antibodies cross-reactive to both HAs. It was noted that the early human H1N1 viruses isolated in the 1930s-1940s still harbored some of the original epitopes that are also found in 2009 H1N1. Interestingly, while 2009 H1N1 HA lacks the multiple N-glycosylations that have been found to be associated with an antigenic change of the human H1N1 virus during the early epidemic of this virus, 2009 H1N1 HA still retains unique three-codon motifs, some of which became N-glycosylation sites via a single nucleotide mutation in the human H1N1 virus. We thus hypothesize that the 2009 H1N1 HA antigenic sites involving the conserved amino acids will soon be targeted by antibody-mediated selection pressure in humans. Indeed, amino acid substitutions predicted here are occurring in the recent 2009 H1N1 variants. The present study suggests that antibodies elicited by natural infection with the 1918 pandemic or its early descendant viruses play a role in specific immunity against 2009 H1N1, and provides an insight into future likely antigenic changes in the evolutionary process of 2009 H1N1 in the human population.”

Oops.  Not simple.

But the result?

“Over 75% of confirmed cases of novel H1N1 occurred in persons < or = 30 years old, with peak incidence in the age range 10-19 years. Less than 3% of cases occurred in persons over 65, with a gradation in incidence between ages 20 and 60 years.The sequence data indicates that novel H1N1 is most similar to H1N1 viruses that circulated before 1943. Novel H1N1 lacks glycosylation sites on the globular head of hemagglutinin (HA1) near antigenic regions, a pattern shared with the 1918 pandemic strain and H1N1 viruses that circulated until the early 1940s. Later H1N1 viruses progressively added new glycosylation sites likely to shield antigenic epitopes, while T-cell epitopes were relatively unchanged.

CONCLUSIONS: In this evolutionary context, Original Antigenic Sin exposure should produce an immune response increasingly mismatched to novel H1N1 in progressively younger persons. We suggest that it is this mismatch that produces both the gradation in susceptibility and the unusual toxicity”

The better the antibdy fit for the epitope (where the antibody binds) the better the effect, but it doesn’t have to be all or nothing. Mihalovic would probably ask, what good is half an eye, why have half a wing, or half a brain?

He finishes,

“I have never encountered one pro-vaccine advocate, whether medically or scientifically qualified, who could answer even 1 let alone all 9 of these questions. One or all of the following will happen when debating any of the above questions:

- They will concede defeat and admit they are stumped.

- They will attempt to discredit unrelated issues that do not pertain to the question.

- They will formulate their response and rebuttal based on historical arguments and scientific studies which have been disproved over and over again. Not one pro-vaccine advocate will ever directly address these questions in an open mainstream venue.”

I am neither stumped not defeated. I know how to search Pubmed for medical information.

My response directed specifically to the questions.

My arguments are based on modern studies that a 12 year old can find in less than a minute, none of which have been disproved once, much less over and over.

SBM is an open mainstream venue.

I do feel like I just had won Jeopardy playing against Prof. R.J. Gumby; where is the honor in that?

And people wonder why I question the wisdom of allowing naturopaths to function as primary care providers.