Wednesday, 5 January 2011

Autism and Vaccination: A Trench Warfare Scenario

A particular kind of argument that I have noted emerges when both sides in a dispute believe they are right, and the evidence "proves" their case. What seems to happen is a retrenchment, when both sides get dug unto fixed positions, very much like the opposing sides in the Great War, and lobby shells across the no-mans land to try and strike at the enemy. Rationality seems to take a back seat. There is no denying the sincerity of the people involved, but what they do is to seek confirmatory instances which prove their case, while ignoring any data that does not fit.

Imre Lakatos noted this in his seminal paper "Proofs and Refutations", which was a study in the history and logic of mathematical discovery. Given a "monster" which represents a challenge to an existing model or position, the options are:

Surrender - Throw the model away and start again

Monster barring - Reject the exception as invalid, a "monster". This usually involves refining the definition of one or more constructs, to explicitly exclude the exception as a monster. (1)

A case in point last year was a resurgence of the dispute over whether there is any link between vaccines and autism. In September 2010, CBS News reported on the case of Hannah Poling:

Terry and Jon Poling spoke publicly for the first time Thursday about a case being watched by thousands of families with autistic children. "My daughter, who had been completely normal until getting nine vaccinations in one day, was suddenly no longer there," said Terry Poling, mother of 9-year-old Hannah. Hannah Poling appeared to be like many children. At 19 months, her pediatrician noted she was "alert and active" and "spoke well." At that same visit, she got five shots - nine doses of vaccines. She almost immediately developed fever, seizures and severe health problems. Eight years later, the government has quietly conceded that vaccines aggravated a cell disorder nobody knew Hannah had, leaving her with permanent brain damage and autistic-like symptoms. (2)

The first court award in a vaccine-autism claim is a big one. CBS News has learned the family of Hannah Poling will receive more than $1.5 million dollars for her life care; lost earnings; and pain and suffering for the first year alone. Hannah was described as normal, happy and precocious in her first 18 months. Then, in July 2000, she was vaccinated against nine diseases in one doctor's visit: measles, mumps, rubella, polio, varicella, diphtheria, pertussis, tetanus, and Haemophilus influenzae. Afterward, her health declined rapidly. She developed high fevers, stopped eating, didn't respond when spoken to, began showing signs of autism, and began having screaming fits. In 2002, Hannah's parents filed an autism claim in federal vaccine court. Five years later, the government settled the case before trial and had it sealed. It's taken more than two years for both sides to agree on how much Hannah will be compensated for her injuries

In acknowledging Hannah's injuries, the government said vaccines aggravated an unknown mitochondrial disorder Hannah had which didn't "cause" her autism, but "resulted" in it. It's unknown how many other children have similar undiagnosed mitochondrial disorder. All other autism "test cases "have been defeated at trial. Approximately 4,800 are awaiting disposition in federal vaccine court.(3)

The language can be seen to be deliberately slippery. What is the difference between "caused" and "resulted"? It seems the legalese is being used to differentiate between a kind of direct cause - A and only A caused B, and indirect causality, A with C caused B.

There is a difference, but it is one of ignorance. If I give someone penicillin, not knowing that they are allergic to that antibiotic, I may kill them unintentionally, but I have not deliberately set out to do so, and I have given them an antibiotic that is very effective for a good many people. Drug allergy is a good case in point, because it occurs in smaller numbers:

Around 15 per cent of patients hospitalised in the UK report adverse reactions to medication, but less than five per cent of those reports are true allergic reactions (mostly to antibiotics). Of this five per cent, less than one per cent are fatal. (4)

But testing for something which is definitely known to happen - there are no "drug allergy deniers" out there - is in fact incredibly difficult:

Most medications are chemicals that bind with various proteins in our body, called haptens. It's this drug/hapten complex that may trigger an allergic reaction. As a consequence, these reactions are difficult to recreate on the skin or in a blood test, so blood testing for drug allergies is unreliable and inaccurate, with false positive and negative results.

Only penicillin, amoxicillin, sulphonamide and cephalosporin allergy can be checked by skin and RAST testing, and in such cases still has only 50 per cent reliability. (4)

Given this problematic scenario with regard to known allergies, it is probably that any autism / vaccine / genetic indirect causality would be even more problematic. That does not stop Congress Rep, Doctor Dave Weldon, for pushing for more research into screening:

Weldon has long been pushing the government to aggressively work to develop ways to screen for children who might be the most susceptible to ill effects from vaccines. The government has been telling the public for more than a decade that there's absolutely no reason to be concerned about any link. "I wouldn't recommend they say something like that in light of the Poling case and the admission on the part of the government," Weldon said.

While the Poling case is the first of its kind to become public, a CBS News investigation uncovered at least nine other cases as far back as 1990, where records show the court ordered the government compensated families whose children developed autism or autistic-like symptoms in children including toddlers who had been called "very smart" and "impressed" doctors with their "intelligence and curiosity" . until their vaccinations. They were children just like Hannah Poling. (3)

The Poling's had a special advantage, Jon Polling is a neurologist and had co-authored a peer-reviewed study on the his daughter, which was not contested by the government -

Autistic spectrum disorders can be associated with mitochondrial dysfunction. We present a singleton case of developmental regression and oxidative phosphorylation disorder in a 19-month-old girl...

To determine the frequency of routine laboratory abnormalities in similar patients, we performed a retrospective study including 159 patients with autism (Diagnostic and Statistical Manual of Mental Disorders-IV and Childhood Autism Rating Scale) not previously diagnosed with metabolic disorders and 94 age-matched controls with other neurologic disorders. Aspartate aminotransferase was elevated in 38% of patients with autism compared with 15% of controls (P < .0001). ... These data suggest that further metabolic evaluation is indicated in autistic patients and that defects of oxidative phosphorylation might be prevalent. (J Child Neurol 2006;21:170-172; DOI 10.2310/7010.2006.00032). (5)

There was some criticism of Jon Polling for using his daughter (if anonymously) as the subject of a paper, and of a potential conflict of interest. This seems to have stemmed from the "no problem at all with vaccines" lobby, which is a good example of how ad hominem arguments enter the fray, as if somehow because it was his daughter who was one of the test subjects, that his research would thereby be definitely biased.

However, this line of research seems to have been followed up later in the "Journal of the American Medical Association" in an article entitled "Mitochondrial dysfunction in autism." published in December 2010

Objective To evaluate mitochondrial defects in children with autism.

Design, Setting, and Patients Observational study using data collected from patients aged 2 to 5 years who were a subset of children participating in the Childhood Autism Risk From Genes and Environment study in California, which is a population-based, case-control investigation with confirmed autism cases and age-matched, genetically unrelated, typically developing controls, that was launched in 2003 and is still ongoing. Mitochondrial dysfunction and mtDNA abnormalities were evaluated in lymphocytes from 10 children with autism and 10 controls.

Results The reduced nicotinamide adenine dinucleotide (NADH) oxidase activity (normalized to citrate synthase activity) in lymphocytic mitochondria from children with autism was significantly lower compared with controls (mean, 4.4 [95% confidence interval {CI}, 2.8-6.0] vs 12 [95% CI, 8-16], respectively; P = .001).

Conclusion In this exploratory study, children with autism were more likely to have mitochondrial dysfunction, mtDNA overreplication, and mtDNA deletions than typically developing children.

Now this is a small study, and has been seized upon as "proof" that vaccines cause autism. In fact, the author of the study, Professor Giulivi, clearly regards this as a pilot study, as revealed in an interview:

KL: Do you think, based on available science (including your paper) that vaccines cause autism?

CG: We do not have any evidence for this in our study. Our study was cross-sectional not longitudinal so it cannot point to any cause (not just vaccines), meaning we do not have any data supporting one way or another.

KL: "Do you believe your own paper adds weight to any opinion regarding autism causation by any means?"

CG: "No. At this point we do not know if it is mainly genetic, environmen­tal or a combinatio­n of both. Again, with a cross-sect­ional study you get a snapshot of the situation but not how you got to that situation

The author of the interview (Kevin Leitch) is clearly determined to debunk the idea that there could be any autism vaccine link, and notes that this means that the "study in question does not add weight to any hypothesis of autism causation, let alone vaccines." He rightly has also observed that a biological malfunction could cause side effects from causes other than vaccines, such as illnesses, but if it is a weakness to the immune system, why is he so concerned to absolve vaccines from the possibility of being involved?

It is obvious that a study of 20 individuals could hardly lend much "weight" to anything, but equally Professor Giulivi is open to the idea that autism could be "genetic, environmen­tal or a combinatio­n of both"; any kind of complex causality has not been ruled out as rapidly as the author of the interview suggests.

What strikes me is the way in which those people arguing the case for an autism vaccine link jump rapidly to any kind of causal link, and magnify results, while those who deny any link at all seem quite content to defend the status quo.

From my own examination of the situation:

a) there are a number of subsets of biological markers with associations with autism. Fragile X is well known, Mitochondrial dysfunction could well be another. This field is very much in its infancy.

b) At the moment, autism is defined largely on the basis of behavioral markers. This is a major weakness. To take an analogy from evolution, "convergent evolution" is when environmental pressures cause widely differing species to develop the same kind of characteristics - water born mammals, such as dolphins, and fish being one example. The present state of play with autism is rather like classifying creatures by the look of the thing, in which dolphins are a singular kind of fish - by the original Greek etymology, most likely the name means "a 'fish' with a womb".

c) Even when we have biological markers, the small numbers involved, and the complexity of reactions (just considering allergic reactions, and problems of determination) suggest either proving or disproving any causality would be a long way off. However, determining conditions such as mitochondrial dysfunction could help isolate "at risk groups" for whom single vaccines, carefully monitored, would be a better option. However that would not take away all risk, but only reduce it, because any other environmental insult could also cause problems.

d) Better reporting of adverse vaccine reactions is required. In Jersey, for example, in the early 1990s, not only were vaccine batch numbers not recorded properly, there was also no procedural mechanism to enable any reporting of adverse reactions; it was purely the discretion of the health visitor, who would usually suggest taking Calpol, and make no file notes. I don't know if matters have improved, or are any better in the UK. In the USA, Adverse Vaccine report documents can be downloaded and completed by anyone, from health professionals to parents. This is not the case in the UK or locally.

Statistics are only as good as their collection, and while there were no extreme cases of reaction locally requiring hospitalisation, no reliable data is available on any less severe reactions which might have shown a pattern. Part of the problem here is that the medical establishment (less so in the USA) "know" that vaccines are definitely safe, hence don't see the need for proper procedures to monitor that this is true, and then cite the statistics to "prove" their case, without checking the reliability of those statistics.

e) In most cases, I am sure vaccines are safe. But not all vaccines have the same safety record, even if they have the same desired outcome. In 1992, for example, the Urabe strain MMR was withdrawn because of significantly severe side effects - asceptic meningitis (8), which is why more detailed studies are now done on new vaccines to check safety. There is also the problem associated with risk. A minute risk to a population may loom larger to an individual; statistics are good for generalisations over the large population, but general fatality statistics don't tell me what my personal risk would be if I decided to climb Everest, for example, where factors such as my personal fitness might well play a more significant role.

See also Proofs and Refutations: The Logic of Mathematical Discovery. Edited
by John Worrall & Elie Zahar. Cambridge University Press, 1976.


Nick Palmer said...

I saw Ian Evan's link to an anti-vaccine website which looks plausible if you don't have enough background knowledge.

The problem with vaccine conspiracy theorists is they use the sort of thinking that makes people expect to win the lottery, only in reverse.

They skate over the fact that virtually everybody wins with vaccines by not getting the consequent disease and concentrate on the very few who get problems with the vaccine and "lose".

Thus, they criticise some flu vaccines because they contain thimerosal (contains a mercury compound), "live" (weakened virus) or squalene.

In a very few, probably immunocompromised people, the weakened virus is still strong enough to give them the disease. Squalene (a substance naturally present in the human body) is portrayed as a substance that can destroy one's immune system and, in large doses, this can be true but in the very small doses of a vaccine, it stimulates the immune system to more speedily form antibodies to the viral particles - which is what vaccination is for. Once you have pre-existing antibodies to the virus, you are very unlikely to get the disease itself. Dose is the crucial aspect. 10 million gallons of water can drown you but half a litre can form a nice hydrating orange squash.

Thimerosal is put in to multi-dose ampoules to prevent growth of bacteria or fungi between doses. It contains the "neuro-toxin" mercury but so what? It is in a compound. Table salt is made up of two substances - one (sodium) a highly reactive metal that forms explosive hydrogen and caustic soda when it touches water and the other a toxic gas (chlorine) that was used in WW1 as poisonous gas in trench warfare. Yet the compound is vital to life.

I've only posted at length on this because I am concerned that some might follow these websites and choose not to get vaccinated. The websites distort the probabilities by representing the dangers from vaccines as a high probability event whilst simultaneously not mentioning (or skating over) the vastly greater and massively more likely benefits.

TonyTheProf said...
This comment has been removed by the author.
TonyTheProf said...

I've noted the mercury compound problem - yes it is like salt before.

I do think however that not enough consideration is given to tracking adverse vaccine reactions. I don't know if Jersey has improved, but I know that in the early 1990s, there was no proper recording of batch numbers, and no recording at all of any adverse effects.

If people are to be convinced that vaccines are safe, then the apparatus for collecting accurate statistics must be in place.

The very worst thing, in my opinion, that the British government did was to use political muscle to enforce a vaccine regime - namely MMR or no alternatives. France, for example, did not and does not do that.

The British government did it as much for commercial reasons as for scientific ones - (a) the MMR is cheaper to administer and record properly (b) the vaccine manufacturers were wedded to the MMR. Contrary to popular belief, Wakefield never said not to vaccine, he simply said it would be wise to use single vaccines.

Concentrating on the very few who get problems with the vaccines and "lose" is important when a government is so concerned about the public relations part of the exercise that they produce "evidence" that vaccines are "completely safe". That's what all the medical officer of healths say. That is not science, that is PR.

TonyTheProf said...

All drugs contain side effects - my favourite is flecanide (a heart medication) which lists "sudden death" as a side effect. But unless there are figures on the risk factor, the probability of a side effect, it is useless information. To say, as with some vaccines, that they are perfectly safe is to ignore the small probability of serious risk.

But unless you have better research into those "very few", you will not have any good data to test for possible causal factors. Some people are extremely allergic to peanuts. I know someone who is allergic to penicillin peanuts, gluten and dairy products, and mussels. For many people, such combination is unlikely, but unless you know the factors, you cannot assess personal risk. If there is some evidence of compromised immune system in one family member, it would certainly be wiser to opt for single vaccines, available from some doctors in Guernsey and France.

I've posted a long reply, because I am not happy with blanket assurance - such as that by the UK - which seem to be largely politically motivated, and which don't give any assessment of risk at all, and effectively treat people like idiots.

By ignoring the small "very few", governments and vaccine manufacturers are coming down very one sidedly on the position that " it is better for you that one man die for the people than that the whole nation perish".

By acknowledging a very small but very serious problem, they would act responsibly and ethically. This they do not want to do, and it is this which fuels the anti-vaccine sites. The solution is in their own hands.