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Finn Family Immune Toll: H1N1 Vaccine and Narcolepsy in Finnish Children

Posted Sep 01 2011 12:00am

Moomintroll Tove Jansson

By Adriana Gamondes

Due to a “pandemic” of two children infected with a new strain of swine flu after exposure to pigs, the  CDC is  gearing up for the new swine flu, H3N2. .

But then, buzz kill, it turns out that children are at a thirteen fold  risk of developing narcolepsy from the squalene and thimerosal containing H1N1 vaccine available in some European countries.  Naturally, the outbreak is being attributed to genetics. 

A final report from Finnish health officials on the link between the 2009 H1N1 Pandemrix vaccine and narcolepsy confirmed the link, finding a greater risk than their earlier estimate and identifying a genetic risk factor in all patients.

The burning question is,  what precisely about the European H1N1 vaccine is triggering narcolepsy? Genes, squalene, mercury, a combination— or something else? And could it happen here? As Barbara Loe Fisher wrote in 2009,

Oil-based adjuvants (MF-59 and AS03) manipulate and hyper-stimulate the immune system to mount a stronger immune response to the lab-altered virus or bacteria contained in vaccines. However, the use of squalene type vaccine adjuvants, which were allegedly added to experimental anthrax vaccines and made Gulf War soldiers sick, is controversial.

Oil based adjuvants may increase the risk for vaccine-induced chronic inflammation and autoimmunity in some children and adults genetically predisposed to atypical inflammatory responses and autoimmunity. No published scientific studies have examined whether those already suffering with chronic inflammation associated with brain and immune system dysfunction may be at special risk.

After lobbying by Loe Fisher’s National Vaccine Information Center and other organizations, the FDA backed off on licensing squalene.

We successfully made enough fuss abou the potential danger of fast tracking licensure of squalene adjuvants into US H1N1 vaccines under an Emergency Use Authorization (EUA that can be invoked during a declared public health emergency that the Feda Has NOT licensed these adjuvants for the US. There is squalene in the H1N1 vaccine licensed in Europe but not yet in the US. That is not to say the vaccine manufacturers will not try to get the adjuvants inserted into vaccines in the future, but for now we have won on this point.

I took more than a passing interest in last year’s reports of increased incidence of narcolepsy among Finnish children vaccinated for H1N1 with Pandemrix.  I’m part Finn on my mother’s side and the mother of vaccine injured twins.  Ever since I heard Andrew Wakefield muse at the National Autism Conference in 2008 that environmental susceptibilities may actually be linked to immunological strengths within certain ethnic groups, I’ve been paying attention.

My own family wasn’t always so fragile—our ancestors hail from the region of Pohjanmaa, which at the turn of the twentieth century was a mostly unindustrialized region surrounding the city of Vaasa on the west coast of Finland. Our Finnish-born relatives often lived into their late 80’s or 90’s, when the typical American lifespan was about 50. They bore children until they couldn’t anymore and were generally blessed with superhuman constitutions. My 6’5” Finnish great-grandfather died from a hernia he developed while digging a ditch at the age of 87.  My 4’11” great-grandmother, whose surname I carry as a middle name, bore seven children— the last at age 51—and lived to 94. They could hunt, fish, build, ski, sail, train horses, you name it.  Finns are notoriously tough. In temperatures as low as 40F below zero, Finns on skis armed with puukko fishing knives and domestically made submachine guns attacked Russian tanks with primal screams of “Hääka päälle!” (“Cut them down!”) and knocked back the last invasion. To quote Garrison Keillor, the women were strong and the men were good looking.

But according to the spin-doctoring following the outbreak of narcolepsy, it’s amazing this genetically disease-ridden race ever survived. The World Health Organization reported that 30% of Finns carry a gene “associated with narcolepsy”. From The Boston Globe :

A WHO expert panel says of 22 narcolepsy patients tested, all had a gene commonly associated with narcolepsy, a disorder that causes people to suddenly fall asleep but is rarely fatal.

About 30 percent of people in Finland have that particular gene, compared with 15 percent in the rest of Europe, said Patrick Zuber, WHO’s top vaccine safety official.

Last week, Finnish authorities said they had found a nine-fold increased risk of narcolepsy among 4- to 19-year-olds who were given the swine flu shots. In total, 60 children and adolescents contracted narcolepsy in Finland in 2009 and 2010. Fifty-two of them — or almost 90 percent — had received the Pandemrix vaccine.

For some perspective, the wishfully named Pandemrix is manufactured by GlaxoSmithKline. With its vast PR machinery, the company can get the media to report—or not report— pretty much anything it wants about adverse events associated with its products. None of the mainstream press reports include the fact the European version may contain not only thimerosal (which the American H1N1 contains) but squalene as well. The combination of thimerosal and squalene has never been tested for safety in children.  From the European Medicines Agency reporting manufacturer's information :

Caution is needed when administering this vaccine to persons with a known hypersensitivity (other than anaphylactic reaction) to the active substance, an any of the excipients, to thiomersal and to resudes (egg and chicken protein, ovalbumin, formaldehyde, gentamicin, sulphate and sodium deoxycholate.

…AS03 adjuvant composed of squalene (10.69 milligrams), DL-α-tocopherol (11.86 milligrams) and polysorbate 80 (4.86 milligrams)

The suspension and emulsion, once mixed, form a multidose vaccine in a vial. See section 6.5 for the number of doses per vial.

Excipients: the vaccine contains 5 micrograms thiomersal

For a full list of excipients see section 6.1.

From a press release of the German Professional Association of Environmental Medicine (Deutscher Berufsverband der Umweltmediziner – DBU, translation by CSN –  HERE ):

From 26. October 2009

Swine flu vaccine is unsuitable for patients with environmental diseases and other chronic multi-system illnesses.  Pandemrix® poses substantial health risk with respect to mass immunization programs due to the lack of proof of safety.  Because of the producer’s release from liability by the German Federal Government (BRD), the risk of adverse reactions and/or permanent damage due to the vaccine rests with the patient.

The German Professional Association of Environmental Medicine (DBU) has, in spite of press releases from the BRD, the Paul-Ehrlich-Institute, as well as the vaccine producer’s assurances of safety, serious concerns relating to Pandemrix® (GlaxoSmithKline), the only vaccine which has been approved for mass vaccination by the BRD.

The DBU discusses at this point neither the medical use of immunization in general nor the necessity of such measures in the, up until now, mild course of the swine flu pandemic.

Our criticism is directed only against the pandemic vaccine Pandemrix®. 

  • There exists considerable doubt as to the effectiveness of the vaccine: during the licensing phase, the vaccine tested had a 40% higher portion of virus antigen (5. 25µg) than the vaccine (3.75µg) now being delivered. An unequivocal consensus has not been reached as to whether the vaccination should be given once or twice a season !!!
  • There exists considerable doubt concerning the safety of the adjuvanted active amplifier since it is being used for the first time. The vaccine contains 27.4mg AS03, an emulsion of polysorbate, squalene and tocopherol. Sufficient studies are lacking, because in the test phase, only the development of antibody titers was determined as a surrogate criterion, and not any potential adverse reactions.
  • The producer as well as government agencies have concealed the fact that squalene, if used subcutaneously or intramuscularly is an inflammatory immune activation immunogen, unlike when ingested. (Squalene is, among other things, for example, naturally contained in olive oil.)
  • Autoimmune diseases can be provoked by squalene; already existing ones can be activated. Squalene has been connected with the emergence of Guillan-Barré Syndrome (GBS) and is now considered a trigger for Gulf War Syndrome (GWS). In animal studies squalene brought on rheumatoid arthritis.
  • Squalene from food sources is mainly incorporated into membranes in the body. The production of squaline antibodies resulting from an immunization sets off chronic inflammation of the membranes, which explains diseases such as Gulf War Syndrome and also degenerative neurological diseases such as Multiple Sclerosis, Amyotrophic Lateral Sclerosis, Chronic Inflammatory Demyelinating Polyneuropathy and Guillan-Barré Syndrome.
  • The delivery of vaccine in multiple dose ampules is obsolete. In single dose ampules the mercury used for preservation, as in thimerosal – which is included in Pandemrix – would be unnecessary.  Also, mercury has been proven to set off autoimmune diseases.
  • Since the vaccine has not been tested on either young children or pregnant women (Ethics Commission objection), the call to give preference in the first phase of vaccination to precisely this particularly endangered segment of the population represents an improper and totally unjustifiable field test.
  • The vaccine poses a higher risk than the swine flu itself for patients with environmental illness and for patients with compromised immune systems (e.g. AIDS).
  • The vaccine producer GlaxoSmithKline (GSK), according to the contract with the BRD, is largely exempt from liability. In case of damage from the vaccination, the affected vaccinee would have to sue the government and therefore the country of Germany, usually a futile exercise.
  • To avoid the trap of liability, the doctor giving the vaccination must meticulously inform the patient of all risks concerning the vaccination and the vaccine. It is recommended to give this information in the presence of an assistant and to have it be confirmed by the patient’s signature. The explanation should also include the liability features. Also the indication that other, lower risk vaccines are available in Europe and that due to a faulty decision by the German government, they are currently not available to the German population. This information should definitely be included in the explanation.

For general and environmental health considerations the DBU urgently advises against carrying out a vaccination with Pandemrix® ! 

Squalene has been associated with a range of adverse events, from infertility to Gulf War Syndrome among American and British troops who received squalene-containing anthrax vaccines.  Research by Tulane Medical School researchers links the anthrax vaccine to Gulf War Syndrome through the presence of squalene antibodies, as noted in the introduction to their report  Antibodies to Squalene in Gulf War Syndrome ;   military vaccine resource directory :

Date: 2002-07-15 Received August 15, 2001, and in revised form October 26, 2001
We previously reported that antibodies to squalene, an experimental vaccine adjuvant, are present in persons with symptoms consistent with Gulf War Syndrome (GWS) (P. B. Asa et al., Exp. Mol. Pathol 68, 196-197, 2000). The United States Department of Defense initiated the Anthrax Vaccine Immunization Program (AVIP) in 1997 to immunize 2.4 million military personnel. Because adverse reactions in vaccinated personnel were similar to symptoms of GWS, we tested AVIP participants for anti-squalene antibodies (ASA). In a pilot study, 6 of 6 vaccine recipients with GWS-like symptoms were positive for ASA. In a larger blinded study, only 32% (8/25) of AVIP personnel compared to 15.7% (3/19) of controls were positive (P 0.05). Further analysis revealed that ASA were associated with specific lots of vaccine. The incidence of ASA in personnel in the blinded study receiving these lots was 47% (8/17) compared to an incidence of 0% (0/8; P 0.025) of the AVIP participants receiving other lots of vaccine. Analysis of additional personnel revealed that in all but one case (19/20; 95%), ASA were restricted to personnel immunized with lots of vaccine known to contain squalene. Except for one symptomatic individual, positive clinical findings in 17 ASA-negative personnel were restricted to 4 individuals receiving vaccine from lots containing squalene. ASA were not present prior to vaccination in pre-immunization sera available from 4 AVIP personnel. Three of these individuals became ASA positive after vaccination. These results suggest that the production of ASA in GWS patients is linked to the presence of squalene in certain lots of anthrax vaccine. 2002 Elsevier Science (USA)

Squalene is also believed to increase permeability of the Blood Brain Barrier, which could theoretically increase the brain’s vulnerability to exposure to mercury, toxins and any rogue pathogens in the same vaccine or from the general environment. From Rabchevsky et al.  (thanks Teresa Conrick for sharing the above two studies :

Some studies of EAE (experimental allergic encephalomyelitis) in rodents report that peripheral injections of complete Freund's adjuvant (CFA), which contains heat-inactivated Mycobacterium to provoke peripheral inflammation without adversely affecting the CNS, can itself lead to increased BBB permeability to small tracer molecules and certain serum proteins.  

In other words, “genes” may be getting a lot of help from certain vaccine components in triggering various diseases. The “Finnish gene” the press is referring to may be certain HLA alleles (DQB1*0602 and DQA1*0102) which are associated with risk of a range of autoimmune diseases among Finns and, to a lesser extent, other Scandinavians. There are different polymorphisms associated with the same types of disease among other ethnicities. But I think the takeaway message about the "disease association" gene is that it’s not apparently a "cause" of disease on its own :

Although narcolepsy is likely to have a genetic predisposition, the low rate of concordance in narcoleptic MZ twins indicates that environmental factors play an important role in the development of the disease.

 Here's what a book on autoimmune liver disease says about the variant :      ... that it represents susceptibility to autoimmune disease.

What's fascinating is how pharmaceutical and genetic research interests have attempted to recast what are likely to be disease-fighting polymorphisms into disease-linked mutations.  There's not a lot of layperson-accessible material on the disease-fighting properties of certain polymorphisms, but this did show up in a  bizarre report on humans mating with cavemen to acquire a class of disease-fighting polymorphisms which might be extrapolated on in future research:

…hookups with Neanderthals and Denisovans introduced new variants of immune system genes called the HLA class 1 genes, which are critical or our body’s ability to fight pathogens, to the gene pool of modern man.

Pleistocene eugenics aside (yes, one strange theory in the “new eugenics” is that some human ethnic groups are less evolved than others due to more or less caveman miscegenation), theoretically, like cutting Samson's hair, strengths – such as regional disease-fighting polymorphisms— can be doubled back on themselves and turned into weaknesses—disease/autoimmune susceptibility— if people with certain variants are exposed to various toxins. 

Even the methylenetetrahydrofolate reductase or “MTHFR” polymorphism—a genetic variant which should be familiar to many autism families— is associated with limited cancer-fighting properties as well as increased risk of other forms of cancer and oxidative stress. The protection provided by this polymorphism may be “weak”, but the fact that a gene can protect against, for instance, squamous cells in lung cancer to any degree hints it might also turn out to provide some protection against certain pathogens :

In a catalogue of similar polymorphisms, including the "Finn narcolepsy genes" DQB1*0602 and DQA1*0102, these variants are associated with more than 60 diseases (including low measles antibodies after vaccination). One of the substances known to interact with the group of polymorphisms is mercury :

Comparative Toxicogenomics Database (CTD)

The following chemicals interact with this gene:

D003907 Dexamethasone

D008628 Mercury

As a side note,  dexamethasone a powerful glucocorticoid  used to treat inflammatory and autoimmune diseases, has several overlaps with mercury, such as cell cycle arrest impacting  tubulin assembly and damage to mitochondria .

This might seem like a leap in logic, but one of the first things I learned about my Finnish heritage is the  lack of active volcanoes in Finland, at least since the Ice Age. Volcanic ash is known as a chief source of natural mercury deposition in soil. As it stands, Finland is lacking in broad soil surveys for mercury content . This may have been due to the traditional lack of mercury deposition, though limited surveys of certain lakes and peat have found levels to be increasing since industrialization.

 I'm sure this has been asked before-- what if, due to lack of traditional exposure to certain toxins, particular ethnic groups may have less resistance to those particular substances than groups which had evolved over the millennia with exposure, just as, for instance, some isolated cultures could be devastated by diseases carried by Europeans or vice-versa?

 It might partly explain why Faroe Islands children, largely of Scandinavian heritage, responded more adversely to dietary mercury exposure than Seychelles Islands children, though this is bound ot be a gross oversimplification.  For one, it ignores the fact the Seychelles study was funded by the fishing and coal-fired power lobbies and conducted among employees of Starkist tuna, the island nation’s only industry. Seychelles parents may have been more likely to report what was expected by the researchers funded by their employer, especially considering these researchers were studying the effects of the company’s products when consumed by children. Whereas the Faroe study (which found serious cognitive deficits among children born to women who consumed mercury-tainted whale meat in pregnancy) was wholly independent from government or mercury polluting industry funding, the lead researcher who conducted the Seychelles study had been involved in the cover-up of the “Canadian Minimata”—the Dow chemical corporation mercury spills in Canadian waterways which sickened and killed generations of First Nations people who subsisted on locally caught fish (see Jane Hightower’s Diagnosis Mercury .) There is also the fact that residents of the Seychelles islands, which reside in the Indian ocean,  would naturally be exposed to more sunlight and undoubtedly had higher vitamin D levels at critical points in infancy; and mercury exposure in the Seychelles may be somewhat countered by high citrus consumption amongst islanders. The Faroe Islands are halfway between Norway and Iceland—short days, no orange groves. All the same, it still begs the question of whether certain ethnic groups may be more susceptible than others to this or that exposure, whether due to lack of traditional exposure or due to the susceptibility of regional “Samson’s hair” polymorphisms to “Delilah effect” of particular toxins.  It’s probably a moot point that both the Faroe and Seychelle Islands are partly or fully volcanic land masses: mercury content in stone is associated with more recent volcanic activity, and mercury is just as likely to be found in subvolcanic host stone and quartz, such as in Almadén, Spain , which harbors the most concentrated deposits of mercury in the world.

Apparently some of these susceptibilities, such as to celiac disease— which has risen from near zero rates in the middle of the twentieth century to about 2% in modern Finland— are strongly believed to relate to disease fighting polymorphisms

Academy Research Fellow Paivi Saavalainen has conducted much research into the hereditary risk factors for gluten intolerance. He said, “Some of the genes we have identified are linked with human immune defense against viruses. This may indicate that virus infections may be connected in some way with the onset of gluten intolerance.”

The unnamed study in question, which is probably Multiple common variants for celiac disease influencing immune gene expression, is interesting, but it would almost seem as if the viral association was highlighted as PR, since anything virally triggered would be of interest to vaccine manufacturers and therefore the media and could bring attention to a particular study, which it did in this case :

 Abstract, Dubois et al.  

We performed a second-generation genome-wide association study of 4,533 individuals with celiac disease (cases) and 10,750 control subjects. We genotyped 113 selected SNPs with PGWAS < 10−4 and 18 SNPs from 14 known loci in a further 4,918 cases and 5,684 controls. Variants from 13 new regions reached genome-wide significance (Pcombined < 5 × 10−8); most contain genes with immune functions (BACH2, CCR4, CD80, CIITA-SOCS1-CLEC16A, ICOSLG and ZMIZ1), with ETS1, RUNX3, THEMIS and TNFRSF14 having key roles in thymic T-cell selection. There was evidence to suggest associations for a further 13 regions. In an expression quantitative trait meta-analysis of 1,469 whole blood samples, 20 of 38 (52.6%) tested loci had celiac risk variants correlated (P < 0.0028, FDR 5%) with cis gene expression.

The gist of the research was that these polymorphisms were associated with immune protection from various viruses. Other research shows that genetic immune defense against pathogens might not only be impacted by pathogens The same research team had also linked a risk of celiac disease with a disease fighting polymorphism associated with immune defense against bacteria:
 
Evolutionary and functional analysis of celiac risk loci reveals SH2B3 as a protective factor against bacterial infection.

Dubois, Saavalainen et al. Hum Genet 86(6):970-7 (2010) PMID 20560212
 
Celiac disease (CD) is an intolerance to dietary proteins of wheat, barley, and rye. CD may have substantial morbidity, yet it is quite common with a prevalence of 1%-2% in Western populations. It is not clear why the CD phenotype is so prevalent despite its negative effects on human health, especially because appropriate treatment in the form of a gluten-free diet has only been available since the 1950s, when dietary gluten was discovered to be the triggering factor. The high prevalence of CD might suggest that genes underlying this disease may have been favored by the process of natural selection. We assessed signatures of selection for ten confirmed CD-associated loci in several genome-wide data sets, comprising 8154 controls from four European populations and 195 individuals from a North African population, by studying haplotype lengths via the integrated haplotype score (iHS) method. Consistent signs of positive selection for CD-associated derived alleles were observed in three loci: IL12A, IL18RAP, and SH2B3. For the SH2B3 risk allele, we also show a difference in allele frequency distribution (Fst) between HapMap phase II populations. Functional investigation of the effect of the SH2B3 genotype in response to lipopolysaccharide and muramyl dipeptide revealed that carriers of the SH2B3 rs3184504*A risk allele showed stronger activation of the NOD2 recognition pathway. This suggests that SH2B3 plays a role in protection against bacteria infection, and it provides a possible explanation for the selective sweep on SH2B3, which occurred sometime between 1200 and 1700 years ago(HERE)

Recasting regional disease-fighting polymorphisms which exist in various cultures as disease-linked genes may be a way to sell drugs and biologics.  For example, a polymorphism carried by 30% of people with Asian heritage, ALDH2, is associated with "Asian flushing" (response to drinking alcohol). Though the ALDH2 deficiency is also associated with protection from certain forms of cancer, the specific association between ALDH2 deficiency and increased risk of esophageal cancer is currently being broadcast in order to peddle Convivia and other drugs .   The risk of the cancer is much higher in people with the polymorphism, but seemingly only among those who drink alcohol alcohol .  It’s possible that those who avoid alcohol could enjoy the disease-fighting properties of the variant and there seems to be no investigation of the long term risks of making those with ALDH2 deficiency Round-Up (alcohol) Ready.  

Maybe in terms of some genetic variants, you can have your cake and eat it too—have your disease fighting polymorphism and live a vital existence—as long as certain groups of people avoid certain exposures. Being that these substances are usually universally bad for everyone but just a bit worse for some, theoretically it shouldn’t be so hard to grasp the principle and implement.  If 30% of an ethnic group carry a particular genetic variant, that variant was geared for survival and only survival. It could not have been a self-destruct button or that race—and the human species as a whole—would never have made it.  To say otherwise is hogwash.   

What strikes me as particularly insidious about the industry campaign to depict everything in human genetic makeup as diseased and borne of weakness—besides the usual effects of scientific hogwash on all fields of learning, culture and human welfare— is how much psychological and physical dependence this fosters on the medical industry.  Talk about a universal blow to human self-esteem.  While commercial science tells us that our greatest source of self-esteem should be its (commercial science’s) contributions, it is meanwhile telling us that, as a species, we’re a genetically booby-trapped epic fail.

But the truth might be the reverse:  as a species, we may be more marvelous and well-designed than we ever knew. If anything, we might curb our enthusiasm about the contributions of commercial science until more is known about the impact of certain technology and wonder a little at our tendency to worship it. For a little Einstein refrigerator magnet wisdom, “It has become appallingly obvious that our technology has exceeded our humanity”. Though preventive medicine and genetic research obviously have their place, the lack of separation from commercial interests—which, without considering long term effects, may snatch at expedient fragments of an investigation in midstream in order to generate marketable technology— seems to increase the risk of medicating away the very features which enabled the species to endure and evolve to begin with.

Adriana Gamondes is an AofA contributor and one of our Facebook page administrators. She lives in Massachusetts with her husband and recovering twins.

 

Posted by Age of Autism at September 07, 2011 at 5:46 AM in Vaccine Safety Permalink

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