Friday, July 16, 2010

In flight entertainment


Slouched on the uncomfortable chair, wondering if he is going to die and wishing he would, the wary traveler and his tiny stomachal stowaway await the boarding call.

His bleak and vacant stare resting on the ceiling, the soul ringing of the emptiness that only a matching absence in the gastrointestinal tract can bring, he ponders: ‘does travelling with the stomach flu qualifies as “in flight entertainment”’.

Inside, he knows, the viral particles are lining his mucosal membrane and, like nanoscopic Mata-Hari, proteic arches extend from the viral envelope to meet the HBGA receptors of his own cell in an ephemerous and mercenary embrace. In rersponse, the membrane reacts by curving into itself. The virus is lowered into a pit until the vacuole buds off on the inner side of the membrane. There, the capsid changes in a way as yet unknown that allows it to fuze with the membrane of the surrounding vacuole spilling into the cytoplasm beyond the content of the viral capsid including a single tiny thread of ribonuceoic acid. Once inside, the viral VPg protein acts as an adaptor and binds the host’s translation initiation factors, allowing the expression of the viral genome.

Now, here is where it gets even cooler. As mentioned, this viral genome is preposterously small and only contain little genetic information. But Norovirii have a neat little trick up their genomic sleeves…

See, somewhere on the gene’s sequence, additional initiation sequences are present. Normally, binding of the ribosomes at these locations would not be strong enough to start transcription.

Nonetheless, sometime, the transcription is interrupted and the ribosome start disassembling. Yet, having slided alongside the RNA it is close enough from the second initiation site that it is able to reassemble there and start the transcription again.

That is termed ‘Translational termination-re-initiation’ and, in effect, allows for the creation of multiple protein sequences from one single RNA. Now, these sequences still are quite similar, but its shortening allows for enough difference during the folding process as for the proteins to fulfill different functions.

Now, at this point, the virus is multiplying actively in the host cell’s as virus so like to do.

When looking at the gut, we see a marked resorption of the microvilli: essentially, the gut is normally like some soft tube that would have been compressed to fit into a smaller diameter. It’s all folded on itself which allows for a much higher contact surface with the content of the intestine. At a lower scale, the membrane of the individual do the same, protruding into what is called ‘brush border’ to increase its surface of contact.

Each one of these folds is called a microvilli and the infection leads to the shortening of these villis, hence, the reduction of the contact surface.

We don’t really yet understand how the virus cause this reabsorption, it might have to do with a rearrangement of the cell’s cytoskeleton but, what we know, from a study last published August, is that infection can reduce the villus surface area by 47%.

This reduction in itself leads to a reduction in the gut potential to absorb nutrient and, because the concentration in solutes remain so high, water flows into the lumen according to the concentration gradient. That in itself can cause what is termed ‘osmotic diarrhea’.

Furthermore, we now know that the infection leads to apoptosis that causes breaks in the barrier, leading to a flow of water through these breaks. Finally, it seems like the secretion of anion into the lumen is simulated by infection, through mechanism as yet unknown, compounding the osmotic diarrhea.

These factors converge, in a messy exercise of fitness, in the accumulation of virus loaded fluids within the intestinal lumen that is quickly evacuated, shedding the virus into the environment, more precisely on my in-flight neighbor if he doesn’t stop jamming his elbow in my, oh so tender, right flank.


Interestingly, despite Norovirus importance as a human pathogen, many of these details are just now being discovered. We can not grow the virus in culture, which has slowed its discovery and make studying it difficult. Still, a similar virus has recently been discovered in mice that is cultivable and seems to constitute a good model so, new avenues are opening in the study of this not so silent killer.

And that, my friends, promise many very cool findings. Still, would it kill the pilot not to shake this goddamn plane so goddamn much?

The reptilians walk among us!

The dawn of the reptilians (really, this should be the title of a Hollywood blockbuster):

Sometime, you don’t feel like half-assing around with lukewarm conspiracy theories. Sometime, you feel like slapping a pair of goggles on and drive full-throttle into crazy-land.

There you’ll probably meet David Icke, he has been living there so long, he has probably been elected as the fucking mayor or something…


The idea of reptilian humanoid is certainly not new by any stretch : early in the UFO phenomenon, before the greys cemented their hegemony, reptilian visitors were quite popular inhabitant of the flying saucers such as in the account of 1967’s abductees Herbert Schirmer or a passage in Brad Steiger ‘Flying Saucers are hostile’ in the same year.

More down to earth, it had been hypothesized, for example by no other than Carl Sagan, that, if not a fortuitous asteroidal encounter in the end of the cretaceous, a highly intelligent specie of dinosaur might have one day evolved that would fill our ecological niche. Troödon formossus that lived at this period and had one of the largest brain to body mass ratio of all dinosaurs, is a favorite candidate for such thought exercise such Dale Russel and Ron Séguin rather hopelessly anthropocentric effort published in 1982 : the dinosauroid. Of course, the mass media were not in rest leading to the creation of popular TV series including the ‘Land of the Lost’ that for three seasons, from 74 to 76, described the reptilian sleestacks, ancient descendants of the dinosaurs, and V, were the invaders were extraterrestrial reptiles adopting a human appearance as part of a conspiracy to take over the planet.

Interestingly, each of these two series seem to have inspired a current in reptoid ‘research’: John Rhodes of the ‘Reptoids research center’ started in the mid-90ies a series of article where he described the reptilians as of terran origin, a convergent line of evolution that produced an intelligent species of cave dwelling rather pacific creatures that only rarely interact with humanity, one could call it the ‘Sleestack version of reptoids’. Of course these creatures should have reached sentience millions of years before any of our ancestors thought of picking up any sharp stick and yet there are, for some reason, the one confined in caves. The reason for this colossal waste of a head-start are, as of yet, unexplained satisfactorily.



And then came David Icke.

And then came David Icke whose paranoid depressing views seem more inspired by V’s visitors although, following the pattern of cross-pollination common to many crackpot theories, he seems quite happy to believe in just about any far-stretched story that is blown his way. Indeed, in David Icke’s world, the reptilians are invaders from the Draco constellation. Arrived on Earth, they establishing themselves at the center of the Hollow earth (the entrance is in Antarctica, apparently) and chilled-out for a while. Then, following a scenario inspired by Zecharia Sitchin, they jump-started the Babylonian civilization that came to worship them as gods, under the name of Anunnaki. Then, because it seems like it’s all any galactic traveler is about, they cross-breed with humans, inspiring the Biblical account of the Nephilim, a story we already heard from the Raëlian cult that itself plagiarized it from Jean Sendy. There was two offshoot of note of these breeding programs: the first one was the production of a human race destined to act as slave master, the Aryans (yes, these guys). The second was the establishment of lineage of individuals able to adopt a human guise upon consumption of human blood. These hybrids bloodlines were then able to acquire leadership position and slowly take over the control of the world, Charlemagne was such a reptilian agent, for example and so is the British royal family to these days as well as the Bushes and presumably any politician or head of state successful enough to be on the news. From this position of power, when not and indulging in child sacrifice and pedophilia (even if it should arguably be called bestiality), the Reptilian advance their agenda, basically, promoting the New world order so dear to the Far Right, as outlined, apparently, in the (well known hoax and best seller of anti-Semitic literature) protocol of the Elders of Zion. Also, the Reptilians come from the constellation Draco, but the Draco constellation from another dimension. So, when Satanists are summoning demons, they are actually bringing Reptilians from this dimension (the fourth one, if you were wondering). Add to that that peculiar British fascination for Lady Di’s death and the idea that the Holocaust apparently did not happen and you might begin to scratch the surface of David Icke’s world view.

At first, the reactions to these ideas were mixed, to say the least, and some people argued that ‘shape-shifting invaders that secretly rule the world’ was just a codename for ‘the Jews’. After all, anti-Semitic conspiracy theory, while not objectively much more sensical, do have a certain credibility born of ancienity and familiarity and, certainly, Icke, between his interest for ‘Aryan race’, his use of anti-Semitic material and his flirt with Holocaust denial, was quite suspicious. But, to these naysayers, Icke was prompt to offer a correction: he really meant actual, literal, invaders from outer-space that shape shift and secretly rule the world. The Jews are just working for them (world-wide conspiracy arguably is a busy business and sub-contracting seems indispensible).



What about the evidences?

Because Icke’s conspiracy has phagocyted so many conspiracionist and pseudo-scientific ideas, most of the evidences Icke can provide sound eerily familiar: He appropriated, for example, a lot of Sitchin’s discredited demonstration. Similarly, the proofs he offers for the secret control of the world by a shadow government of aliens are pretty much copy-pasted from similar conspiracy by the Jews or the Free-masons. The rare bit of truly original evidence offered by Icke and followers is a few poor quality videos in which the subject is described as displaying reptilian physical traits.

So, what should be the skeptical conclusion? Well, it is not possible to totally dismiss the ideas. In fact, many of this conspiracy ‘theories’ are, by nature, unfalsifiable as any absence of evidence is perceived as proof of the secrecy of the conspiracy; any contradictory evidence is but a plant, part of a cover-up by these all powerful illuminatis… So, yes, it is always possible that we all (but Icke and a few of what he terms ‘red robes’) are pawns, shepple, unable or unwilling of seeing the hidden truth. Yet, the default position should be that things are, actually, what they seem to be, that no hard proofs have been offered of the presence of these alien lizards simply because they are not here.

The videos, for starter, are pretty inconclusive. Why would these consummate liars suddenly let slip the mask? And, if this control is so flimsy, how come these slips only happen around cameras? How are they able to fool their entourage 24/7? Isn’t the idea of an artifact of video compression and pixellization much more likely?

As for the more general conspiracy… the world is complicated and messy. Facts are lying all over the place. By carefully selecting and cherry-picking what facts to present, one can tailor what they appear to say in an apparently coherent narrative, one of secrecy and secret conspiracies, a bit like, by cautiously selecting which monument to choose, one can appear to paint a pentagram on a metropolitan city grid: to me, the evidences are way insufficient to warrant seriously challenging the default position.



So what? (shape of a conclusion)

This situation does put the skeptic (at least me) in an awkward position: On one hand, the utmost silliness of the idea, it’s joyous cooptation of the craziest most outlandish claims that the internet can offer, give to Icke’s ramblings an almost pythonesc quality that is quite comedic and a more than a little sympathic. Indeed it did inspire British writer Warren Ellis some rather funny pages for the comic Hellblazer (scroll down, true believer).

Yet, under this superficial crust of clownish make-up, there is the foul smell of the vilest of the vile, the equally joyous bedding of the sewer tainted ideology of the far right, from the British National Party to the KKK. So, yeah, we can laugh at the idea of people turning into humanoid reptile, but, my friends, let’s not forget what Ionesco had to say about people turning into Rhinoceros...


Hellblazer 143, written by Warren Ellis and drawn by Marcelo Frusin, very, very good stuff...

Tangled lovers: the true tale of siRNA…

Recap:

So, last time, I mentioned how DNA was transcribed into RNA that itself was translated into proteins. We also spend some time on how complementary nucleotide sequences bonded each others (if you are not familiar with the subject, go check it out, we will wait).



Role in gene regulation:

So, if you look at the second step of the central dogma, you can see the recently translated mRNA floating around, patiently waiting for the ribosomal complex to bind it and start transcribing it into protein…

Except that, at the last minute, a short RNA sweeps in and bind the mRNA instead. This block the binding site for the ribosomes and prevent the translation (that is called “RNA interference”).

Worse, viruses are the only organisms whose genome can sometime be found in the form of double stranded RNA so these structures are quickly targeted by dicer proteins that cut them into pieces.

This constitute a somewhat crude but a efficient mechanism to control the level of expression of a gene referred to as “posttranscriptional gene silencing”.

Bacterial CRISPRs:

A very cool application of RNA interference might be immunological.

There are sequences, present on most bacterial genomes, called (Clustered Regularly Interspaced Short Palindromic Repeats) that, when they were first discovered, nobody really understood what they did. Then somebody noticed that, at their center, was a short sequence that looked really like that of a bacteriophage (the term for any virus infecting bacteria).

At which point it was a small step to think that these CRISPRs might be involved in RNA interference with their matching sequence on the viral genome and, sure enough, it was quickly demonstrated that the presence of these sequence correlated with resistance against virus invasion. Moreover, knocking down these sequences rendered the previously resistant bacteria susceptible to infection.

It was a pretty cool find all by itself. But then, somebody decided to take a susceptible bacterial culture, infect it with a bacteriophage and look for survivors. Sure enough, a few bacteria did survive infection. Furthermore, when challenged again with the same virus, all the descendants from these survivors appeared resistant to the virus. At this point, looking back at the genome, the researcher noticed that the bacteria now harbored a shining new CRISPR region it didn’t before the infection, and this region did correspond to the sequence of the virus. In short, they had evidences suggesting that the bacteria, somehow, had been able to acquire part of the virus sequence and use it for protection. Technically, you could describe that as ‘acquired immunity’, if the term was not already taken.

In addition to this complementary DNA sequence, the CRISPRs are surrounded by a variety of sequences, termed Cas (for CRISPRs associated genes). These genes are extremely heterogeneous and code for a variety of proteins, more than 40 families of Cas have been described, several of which appear to be DICERS, molecules that specialize in cutting nucleotide sequences. Interestingly, Cas are very well distributed among the bacteria suggesting that a lot of horizontal transmission, gene passing between bacteria, is taking place.

The means through which these viral sequences are then integrate to the bacterial genome are not as of yet known. It is likely that some Cas are responsible, it might, for example, be an additional function of some of the DICERs…

Immunological role:

Interestingly, a mechanism, called RISC, had been discovered in eukaryote before, and it’s really cool:

So, here you have your strand of viral RNA, it’s either double stranded or it is single stranded, but will become, if briefly, at some point in the process of copying itself.

At any rate there is this protein floating around in the cytoplasm called a DICER (cool name, right? It’d make a great name for a super-hero. Or maybe one of these knives sold on TV infomercial). Anyway, the DICER’s job is to find and bind such a double stranded RNA and then, as its name suggest, it cut if off into pieces (ok, it would be an old school super-hero, like the Spectre but maybe he could have a team-up with the Punisher, or something). But the DICER’s job doesn’t stop there, it also pick up a small portion of the RNA strand that he just made a mess of.

Then the dicer bound by a molecule termed TRBP (for human immunodeficiency virus Transactivating Response RNA-Binding Protein) that apparently functions as a matchmaker, recruiting the Argonaute2 protein.

This second protein loads the RNA sequence into its groove. Then it destroys one of the strands and starts floating around in the cytoplasm, still carrying one strand of the RNA, now termed the “guide strand” the DICER-TRBP helped loading. This way, when it encounters a RNA sequence which is complementary from the guide strand, this complementary sequence (the “passenger strand”) will be bound and then cleaved and, in effect, the RISC acts as a molecular targeting system for the argonaute2 protein.

This mechanism presents some similarities with the one recently described for the CRISPRs. Furthermore, it is very well spread all over the eukaryotic kingdom, it is very common and im)portant in plants, but has also been described in humans. This suggests that it involved in a common ancestor, far away don’t the evolutionary tree. In fact, it is even quite possible that this ancestor was a bacteria and that the RISC system is but an evolutionary refinement of the good ol’ CRIPRs…

A few stuff about molecular biology.

I wanted to talk about a few of the really cool stuffs that one can find out by studying molecular biology.

These can be really neat and often are living witnesses of our most distant evolutionary past, carried deep in the heart our own cells.

But, yeah, when I started about thinking how to write up the coolest ones, I realized that I’d probably do a small recap of the bases, so here it comes.



Recap, the central dogma of molecular biology:

What we refer to as ‘the central dogma of molecular biology’ was first proposed by one Francis Crick of doubly helical fame. In short, it describes how genetic information is contained into DNA, how this DNA is transcribed into RNA and how this DNA is then translated into proteins.

One could, with a little smirk, describe it as the product of a simple time, because quite a few exceptions to this dogma have since been found, as always, Nature is a messy place. Still, it works well enough.



Now, the four DNA bases tend to bind to each other in pair: cytosine tends to bind guanine and thymine tends to bind adenine (in RNA, thymine is absent and instead another closely similar molecule, uracil, binds adenine). That means that complementary sequences will naturally tend to bind each other: CGTACGTA will naturally tend to bind GCATGCAT sequences, in fact, this is the combined forces of all these tiny base-to-base liaisons that bind together the two branches of the double helix (in fact, two complementary sequences of DNA).


Here you see the two helices bound together by the meeting of the nucleotide pairs

(image ruthlessly pilferaged from Genomes -third Edition- by T. A. Brown; University of Manchester)



Another point worth mentioning is that both lesion are not equal, cytosine that interacts with guanine through three hydrogen bonds will form stronger bonds than adenine that only interacts with thymine or uracil through two hydrogen bonds.



Here are the formula of the five nucleotide bases, also showing the interaction between the DNA base pairs, weaker between adenine and thymine or uracil than between cytosine and guanine.



The transcription and transcription termination in prokaryotes.

Now, imagine, if you will, the single lonely chromosome of a simple bacterium. Getting closer, we can discern the long flowing chain of this double stranded chain of DNA. Floating by is the bulky shape of a RNA polymerase, a complex of 5 different sub-units. Another molecule, the Sigma factor 70, pass by and start interacting with the RNA polymerase. These interaction slowly nudge the RNA polymerase toward the chromosome, and more precisely toward the -35 box (a sequence located 35 nucleotide upstream from the gene of interest). Then, the RNA polymerase finally bind the DNA, forming the ‘promoter complex’. It then starts pulling the DNA toward it, in the process, separating the two branches downstream and accumulating the energy it will need (imagine unwinding two rubber bands, tightly wound one on to the other). This lead to the formation of a ‘open promoter complex’ where, just uphead from the transcription complex, one may observe a short region where the two strings of DNA are separated (we call it the transcription bubble), a bit like the zipper of an overloaded bag, where the two half of the zipper start to break apart.

Inside the bubble, base pairs are added on after the other that match the ones on the DNA strand and, slowly, the RNA messenger is constructed that form a sequence complementary to the DNA. The two strands interact with each other, forming an ephemeral liaison that help stabilizing the transcription complex.



Here is a nice schema to illustrate this (taken from Principle of Biochemistry, Lehninger et al., 2000: get it, it’s a standard).



But now, it’s when it becomes really cool. At this point, the RNA arrives at the end of the gene. How does the transcription complex ‘know’ where to stop?

Well, there are two big ways in bacteria and the coolest part is common in both. You see, by the end of the gene there is what we call a ‘palyndromic sequence’. In English, a palindrome is a word or a sentence that can be read from both left to right and right to left, like the word, ‘radar’ for example. In molecular biologist English, a palindrome is a sequence that is identical when read in one direction to the one on the complementary strand when read in the opposite direction: for example CGTTAACG is palindromic, its complementary sequence would be GCAATTGC which, read from right to left, become CGTTAACG.

The importance of this palyndromic sequence is that it is complementary with itself. Look at it, the first pair (C) will bind the last one (G), the second pair (G) will bind the second to last (C) and the two Ts will bind the two As

Now, if we have a long palindromic sequence, the left and right portion of the sequence will tend to bind with each other, forming what is called a ‘hairpin loop’.






This hairpin loop fold onto itself, instead of interacting with the DNA sequence, which would stabilize the transcription complex. This destabilize the whole complex and slow down the transcription process.

Then, two things can happen. In about half the genes, this sequence is followed by a long sequence of adenine. As we mentioned, the adenine-thymine and adenine-uracil pairs are weaker than the cytosine guanine ones. This further weaken the binding of the mRNA on the DNA strain to the point where the two strands break up, interrupting the transcription process.

The other relies on what is call a Rho factor which is another helicase (it breaks bond between nucleotide pair). Essentially, he Rho binds the transcribed DNA sequence a bit upstream from the RNA polymerase and start moving in the same direction at roughly the same speed. Normally, the RNA polymerase own migration along the DNA strand allows it to stay ahead. But, as we mentioned, the RNA polymerase is slowed down at the hairpin level, this allows the Rho factor to catch up and start breaking up the pair lesions at the level of the RNA polymerase. This, in turn, leads to the breaking up of the transcription complex and the end of the transcription…


Conclusion

So, there you go, it’s certainly not complete, but reading that should give you the basis for understanding the really cool stuff I’d like to talk about next (starting with small interfering RNAs).

Vaccination and the “autism controversy”


A tale of victory:

The child squirmed as the small two-pronged needle penetrated his arm and started to cry. With a dexterity born from a long experience, the volunteer adjusted his grip and quickly jabbed the needle five more times before nodding to the mother. Behind her, the whole village had lined up in the October heat of the Southern Bangladesh island, patiently waiting for their turn to be vaccinated.

A few hundred yards from there, the two year old Rahima Banu Begum turned in her feverish sleep. She had been diagnosed with a case of variola major, the most virulent form of smallpox, and now the race was on to vaccinate has many people has possible to protect them from the infection. The strategy was to quickly encircle the outbreak into a cordon of immune subjects that, like a firebreak to the fire of the epidemic, interrupt its transmission to the rest of the country. This approach had been devised in Central Africa by William Foege and had been proven very successful in the past. It was to be again this time: the year was 1975 and young Rahima was to be the last person ever to be infected in a wild outbreak of variola major. Then, two years later, Ali Maow Maalin, a 23 years old cook and volunteer vaccinator from Somalia would be the last person to be infected by a natural outbreak of variola minor. Apart from the tragic laboratory accident that would claim the life of Janet Parker in 1978, this would be the last time that an outbreak of smallpox would be observed on the surface of the world.

And there it was. Smallpox, the disease that had been plaguing mankind for at least 5000 years, the disease that once claimed the life of own in 7 European child and that of more than 300 millions people in the 20th century alone –three times the death toll of the black plague, smallpox was gone.

This, however, was only one of vaccination remarkable successes. In 1952, for example, the year Jonas Salk first tested his polio vaccine, 38,000 cases of infection by the virus were reported in the U.S alone, killing thousands and leaving more than 20,000 disabled. Today, vaccinations has allowed this number to drop to about a thousand case annually reported world-wide, mainly from developing countries in Africa and Asia were the vaccination efforts is impaired by war and extreme poverty.

Measles were also fought back: In the decade before the measles vaccination program began, an estimated 3–4 million cases were reported each year in the United States resulting in 400 to 500 fatalities and thousands of people left disabled from the encephalitis. Nowadays, these numbers have been driven down to the mere hundreds of new cases annually and it is considered that the virus is no longer endemic in the U.S.

Similarly, diphtheria which once claimed 13,000 to 15,000 life annually (out of 100,000 to 200,000 cases) has only been reported about twice annually in the 2000.

And, for many pathogens, herd immunity has been achieved (herd immunity is the idea that if a high enough proportion of the population is immune to a pathogen, the pathogen will not be able to find a susceptible host to infect before being cleared from its present host and, hence, any epidemic will be unable to take hold and will die of quickly).

The autism controversy:

And yet these successes bore the seed of today’s crisis: We got complacent. In just two generations we have forgotten the time of our parents and grand-parents when every child could point you at the tombs of half a dozen former playmates, when infections were an all too real and tangible part of life. We have become complacent and forgot of the enemy that was only asleep.

The anti-vaccination movement is nothing new, of course, even Jenner’s first experiments with vaccinia were met with suspicion. And, if this movement subsided once confronted with the incredible successes that vaccination brought (in the 50’s, the figure of Jonas Salk, developer of the Polio vaccine, was both famous and celebrated) it never completely went away. For example, some conservative sects, such as the Quakers, did oppose the use of vaccine on religious grounds since the beginning (they perceived it as a attempt to circumvent God’s wrathful judgment) and some have still to change their stance on the subject. At the opposite end of the spectrum, in the 70ies, anti-establishment and a desire to go back to nature fed a small drop in vaccine rates among the most liberal minded segment of the population.

But this drop was short live and today’s anti-vaccination movement, gaining speed mostly since the late 90ies, centers around the problem of autism.

Autism is actually only one aspect of a family of related conditions that constitute what is now defined as the ‘Austim spectrum disorder’. These conditions are characterized with a variable degree of impaired socialization and communication. Development is also impaired and, in some cases, the autistic patient is limited to a restrictive pattern of behavior, often limited and repetitive. In the case of Asperger syndrome, these limitations actually often lead to very specialized interest for the patient that can, in fact, end up being quite brilliant in his field of choice.

As we can see, the definition of these conditions is quite vague, and relies heavily on the subjective opinion of the practitioner. Indeed, it has been argued that autism was more a matter of degrees than a black and white condition, with some people being further on the autistic spectrum than other and only the most severe cases being an actual handicap. As an anti-social nerd I can see merit in this definition.

There are real practical consequences to this definition problem: it is known that the prevalence of autism (the number of known cases of autism) is greatly increasing every year and was rose by more than 5 times from 1997 to 2007, rising the fears of an ‘epidemic of autism’ and the anti-vaccination movement has been very fond of blaming this rise in prevalence on vaccines. In fact, it is often considered that the current anti-vaccination movement was launched by the study by Andrew Wakefield et al., published in 1998, by the prestigious British medical journal “The Lancet” that linked MMR vaccination to a collection of bowel symptoms as well as to the development autism. Presumably, according to Wakefield, the vaccine was causing breach in the gastro-intestinal barriers through which toxin could enter and damage the neurological system.

It has since been revealed that Dr. Wakefield’s studies were funded by a group of lawyer engaged in a class action lawsuit against vaccine manufacturers, an obvious conflict of interest that Dr. Wakefield failed to reveal at the time. Even worse, it was soon made clear that he discarded and falsified data to suit his hypothesis. Nowadays, 10 out of 12 of the original authors of the study have retracted themselves from its conclusion. Furthermore, as of early February 2010, the Lancet officially retracted the article from the published record, and, really, they can’t do much more to acknowledge their initial mistake without offering every one of their reader flowers and a nice dinner. Despite this some people are still heralding Wakefield as some scientific hero and not only putting trust in his work, but actually preferring it versus the consensus of the rest of the scientific establishment.

Another suspected link between vaccination and autism is the ethylmercury thimerosal (sometime spelled thiomersal), a preservative added to some vaccine preparation until the late 90ies. Because dimethylmercury is a very nasty neurotoxin, some people have suspected the thimerosal in vaccine of being a cause of autism. Indeed, in 1998 and 1999, the FDA recommended as a precautionary measure, its replacement in vaccine products. A statement that the anti-vaccine movement sometime claim as a vindication of their agenda. Of course, there is quite a lot of problem with that theory. First of all, as said, thimerosal is a different compound than dimethylmercury, with different proprieties: mainly, it does not accumulate in the organism and, has such, should not be able to cause problems. Also, even after a full vaccination regiment, the total amount of mercury a vaccination would bring would be insignificant compared to that obtained through the diet, especially one rich in seafood. Furthemore, the neurological damage caused by mercury poisoning –mostly memory loss, insomnia and emotional instability- are well known and characterized and have nothing to do with any of the symptoms of autism. Finally, thimerosal has been withdrawn from vaccine products in the United States since the early 2000, and does not seem to have ever been incorporated in the MMR vaccine that so often seems blamed for autism (CDC). If really it was the cause in the spike of autism, the so-called autism epidemic, one would expect this “epidemic” to stop and yet, it didn’t even slow down (Gerber and Offit). Nowadays aluminium, than sometime replace thimerosal in the vaccines, is often charged with having the effect once attributed to mercury, but with even less logic behind it…

One last rationalization by the anti-vaccination movement is the idea of “vaccine overload”, the concept that injecting so many different antigen in such a relatively short lapse of time will burn out the immune system. This idea is flawed in several ways. First of all, it illustrates a misunderstanding of how the immune system works: antigens are captured and exposed to circulating T and B cells. The ones whose surface receptors correspond to the antigen will be activated, improve their specificity for the antigen and become longer lived. There is, indeed, a phase called ‘clonal expansion’, in which the number of cells does, in fact, increase but this increase generates between 10,000 to 100,000 new cells. It may sounds like a lot until you compare it to the 4 to 10 billions of white blood cells normally present in a liter of blood. Furthermore, the fact is that, while the number of different vaccines child are getting immunized against, grow regularly, our technology and understanding of the immune system grow even faster. In effect, this allow to obtain protection with lower and lower doses of the antigen and the amount of antigens delivered in the fourteen vaccines administered to U.S. children in 2009 correspond to less than 10% of what it was in the seven vaccines given in 1980 (Gerber and Offit). In fact, the immune system is always confronted to a number of antigens. Every molecule of a significant size that make it to the blood is treated by the immune system as a potential risk. This is the reason why any prolonged exposure to such an antigen might result to allergy problems. Compared to this myriad of antigens, the ones contained in the vaccines are insignificant in term of load on the immune system, it is estimated than a children get confronted to les new antigens over the course of a full vaccine regiment than he will encounter in one normal day (Gerber and Offit). And, of course, the anti-vaccine movement has yet to explain the relationship between the immune system and the neural system that would explain the development of autism.

In reality, there is no scientific reason to believe that vaccination would cause autism. There is no theorical basis on how vaccine, either their immunological component or any adjuvant, would interfere with the development of synaptic connection. From an empiric point of view, no practical association was ever found between vaccine children and the development of autism. Wakefield still claims to have found such correlation, both in his 1998 paper and in later articles, but so far, he has failed to convince even a small portion of the scientific establishment. On the contrary, the 2004 consensus report by the Immunization Safety Review Committee found no such link (Unknwon).

In fact, there is no particular reason to blame vaccine for the seemingly rise in autism prevalence in the last decade. It is not like autism is the only factor that changed. After all, Jim Carrey started his cinematographic carrier in 1983 and, as far as we know, there is just as much reason to consider the rise in autism to be due to an increase exposure to Jim Carrey’s antics rather than to vaccines. Indeed, while many studies have been conducted that show no relationship between vaccine and autism, I am not aware of any such study clearing Mr. Carrey…

In reality, we don’t even know that autism prevalence has really been rising: when we look at the rate of autism constant among all age class, we found it to be grossly constant (Brugha, McManus et al.). However, if the 5 fold increase prevalence was due to an increase in incidence, young children getting the condition, you would have expect a much larger proportion of children under 10 to have it. Because this rate is constant among class age, the increase in prevalence is most likely not due to new children developing the disease. As was said, the definition of autism is fluid and subjective and it is very likely that the observed rise in autism prevalence is most likely due to physician increase willingness to diagnose somebody as being on the autistic spectrum.

It is a bit like government sometime do, hardening the criteria for being classified as ‘unemployed’ or increasing the poverty threshold and then parading how successful they were at stomping out unemployed and poverty…

The current anti-vaccine movement:

Of course, this lack of evidence does not stop the very dedicated anti-vaccination movement. Indeed, the lack of allegiance to one explanation as to how vaccine would cause autism is quite revealing. In contrast with the methods of science that builds hypothesis and then test them against facts, anti-vaccers start from their conclusions, that vaccines are evil and cause autism and then make-up post-hoc rationalizing for their belief. In this aspect, they are not different from any number of apologetic and denier movements.

Let’s make it clear here that, in most cases, the core-members of the anti-vaccination movement are absolutely sincere in their beliefs. In some sad case, blaming the vaccine is a coping mechanism, a release for the anger and guilt felt upon the diagnosis (Fortier and Wanlass). Yet, this sincerity does not change the fact that this position has no backing in science. This is particularly of concern because that anti-vaccine movement has been able to gain a wide-spread audience.

When Actress and vaccine activist Jenny McCarthy participated to the “help our vaccine” protest, more than 8500 people assembled beside her and she has since been given her own talk-show, giving her not only access to an even more massive audience but an additional credibility to her message.

And that is the crux of the problem, as long as the anti-vaccine crowd was a tiny minority, they were protected behind a cordon of herd immunity. The pathogens, to simplify, could not find a susceptible carrier to arrive to the non-vaccinated children. But now, the number of un-vaccinated children is rising, all because of a fear that has no basis in facts. Right now, the drop in vaccination rate has reached the point where it, in place, is starting to compromise herd immunity. The number of children coming off with disease they should have been vaccinated against is rising regularly and we are starting to see the first fatalities (Farley) (a fact that the anti-vaccers like Jenny McCarthy do not contest but consider an acceptable price for their ill-conceived crusade (Kluger). And it might become even worse. Of course, the days of old, when infections where rampants and claiming the life of many children, will not come back. Of course the public we remember the usefulness of vaccines long before we reach that point, the problem is: how long is it going to take and how many more children will have to die an easily preventable deaths before it happens?

All for a fear that has no basis in facts. All of this because we have become complacent and let ourselves forgot the days of rampant infections.


Here are some of the references I used:


Brugha, T., S. McManus, et al. (2009). Autism Spectrum Disorders in adults living in households throughout England Report from the Adult Psychiatric Morbidity Survey 2007, National Statistics - NHS.

CDC (2009). "Understanding MMR vaccine safety."

Farley, T. (2010). "What's the harm in vaccine denial?" Retrieved Feb. 2010, from http://whatstheharm.net/vaccinedenial.html.

Fortier, L. M. and R. L. Wanlass (1984). "Family Crisis following the Diagnosis of a Handicapped Child." Family Relations 33(1): 13-24.

Gerber, Jeffrey S. and Paul A. Offit (2009). "Vaccines and Autism: A Tale of Shifting Hypotheses." Clinical Infectious Diseases 48(4): 456-461.

Kluger, J. (2009). "Jenny McCarthy on Autism and Vaccines." Time.

Unknwon (2004). Immunization Safety Review - Vaccine and Autism, Immunization Safety Review Committee