Tag Archives: virus

Vaccines

A lot of people online seem to be afraid of vaccines. The belief that they are harmful seems a lot more pervasive than I had realized. I will have to delve into quite a few scientific papers to be sure I am giving this subject a fair examination. However, before I get into the science, let’s deal with the obvious; a lot of anti-vaccine people are naturally distrustful of any evidence you can provide them. What I call science, they call “Big-Pharma” propaganda. It doesn’t matter if it’s a government funded study, the FDA, or even an international source like the WHO. To them, these sources are all suspect, but some “natural news” website is totally trustworthy. How plausible is this conspiracy theory?

Big Pharma

A lot of people will claim that vaccines are promoted by these organizations because they’re in the pocket of “Big Pharma”. To be sure, the pharmaceutical industry does spend a lot of money on lobbying, which influences U.S. legislation. What is the outcome of this lobbying however? Does it really appear to have pacified the FDA into looking the other way on unsafe products? Not by any measure that I can find.

First of all, it is incredibly difficult for a drug to get FDA approval. (1) To summarize, a drug starts out with 1-6 years of preclinical testing. If it is one of the 1 in 1000 that looks promising, the company will file an Investigational New Drug (IND) application. Phase I clinical trials test the safety of the drug, and weeds out about 70% of the drugs being tested. This costs about $15 million. Phase II tests effectiveness, proper dosage, and safety, and whittles it down to just 14%. It costs about $23 milion. Then comes phase III, which leaves only about 9% of the original drugs, and costs about $86 million. 8% Make it to FDA approval. All of this takes about 7 to 17 years. After this comes phase IV, which is the post-market surveillance. Even after all of this, the drug can still be recalled after it hits the market. The FDA link also points out that testing requirements have increased over time.

“Over time there has been a clear tendency for FDA regulations and requirements to expand and multiply. In 1980, the typical drug underwent thirty clinical trials involving about fifteen hundred patients. By the mid-1990s, the typical drug had to undergo more than sixty clinical trials involving nearly five thousand patients.”

As the testing requirements have increased, so has the cost of getting a new chemical entity (NCE) into the market. Clearly, R&D is more expensive than ever. (2) If “Big Pharma” really was calling the shots, and willing to increase profits without regard for human life, wouldn’t they be cutting corners and stripping away the costly and laborious regulations surrounding FDA drug approval, rather than letting them increase? Stripping away the costly requirements of clinical trials would increase their profits far more than the promotion of vaccines, which are not terribly profitable anyway. In fact, pharmaceutical companies are increasingly abandoning vaccines, which cost as much as or more than any drug to produce, yet can grant immunity to a disease with only a single treatment. This cuts down on the profit margin considerably, compared with a drug that must be taken multiple times. Additionally, the public hysteria against vaccines has taken its toll on the industry. In particular, the swarm of lawsuits, many unsubstantiated, have added to the cost. The burden of proof for safety placed on a vaccine by FDA regulations is also heavier than for many other drugs. This paper goes into depth over the issues that have made vaccines unprofitable.(3)

Because of all of the companies leaving the vaccine business, the paper recommends congressional action to encourage pharmaceutical companies to produce more vaccines, to compensate for the low profit margin. If not, then companies will continue to abandon vaccines in favor of other products. If this happens, it will be the public, not the pharmaceutical companies who suffer.  It goes on to say:

“Among the four large companies still making vaccines… -none has revenue from vaccines that exceeds 10 percent of total revenue.9 All four companies could stop making vaccines tomorrow without much impact on their bottom lines.”

So vaccine promotion is not so  beneficial to“Big Pharma”. Is this really the cash cow that all of that lobbying money is used to promote, while the costs and regulations on FDA drug approval continue to increase?  In fact, you could make a more convincing conspiracy theory that Big Pharma is actually behind the anti vaxx movement, because they would profit far more from a vaccine-preventable outbreak than they would from vaccines. (4) If you look at the charge that their lobbying is buying them decreased FDA scrutiny, the trends mentioned above just don’t bear this out. Claims that the pharmaceutical industry has turned the WHO into a puppet are even more absurd. If they can’t even control the FDA, how can we imagine that they are controlling an internationally funded organization like the WHO?

I’ve heard others claim that it’s the world governments, not private industry, that are pushing vaccines for some nefarious purpose, such as “population control”. It’s hard to respond to a view of the world that is so distorted. If it pleases them to believe that the world is secretly run by cackling comic book villains, there’s nothing I can do to dissuade them.

So what is all of that lobbying money buying? One thing that does correlate with lobbying expenditure, however, is the price of drugs. With the cost of getting new drugs approved rising, this to be expected to some degree. However, it is possible that they are raising prices by an unfair margin, because everyone looks after their own interests after all. Simply flooding the market with unsafe, untested products would serve their interests far less than simply raising prices. Considering that pharmaceutical companies suffer from legal liability all the time, it’s hard to imagine they would want to expose themselves to even more of it. Even if they did decide to secretly purvey unsafe products, it’s hard to imagine why they would go to great lengths to do so with vaccines specifically, when simply switching to other products is often better business anyway.

What about the scientific literature itself though? There does seem to be an overwhelming tendency for papers funded by pharmaceutical companies to give positive reports on pharmaceutical products. However, on many issues, a majority of papers that are not funded by pharmaceutical companies also agree with them. (5) So you can’t exclude every “pro-pharma” source simply on the basis of funding. Additionally, if a paper can be shown to have good methodology and logic, and constructs its arguments from many sources that are not in question, then the funding behind it should not matter.  This sword cuts both ways as well; some anti-vaccine papers are funded by anti-vaccine organizations. Even Andrew Wakefield had his own interests to further, which are well-known. Would an anti-vaxxer be willing to dismiss these papers simply based on their source of funding as well?

Now, with some rightful doubt cast on the conspiracy theory itself, let’s have a look at the science. This is where it gets tricky, because it has long been acknowledged that vaccines can and do have negative side effects in certain instances. Far from being hidden, this knowledge has been the subject of much discussion in the scientific literature for decades.  So the real question is not whether or not complications exist, but whether or not they outweigh the benefits of vaccines.

Origin of Vaccine Fear

Obviously, there has always been some fear of vaccines, simply because all treatments carry risks. One of the first recognized issues with vaccines was that an attenuated virus in a vaccine can mutate to become virulent once more, in what is referred to as a reversion. In this case, the vaccine may cause the very infection that it was meant to protect against.  This is only an issue with attenuated live vaccines. Other vaccines use a killed or inactivated virus, and some don’t even use the entire virus- just a particular subunit or molecule from the virus. Infection from these is virtually impossible. However, even the live virus vaccines use a weakened form of the virus that is normally harmless to someone with a healthy immune system.  Often, it is an impaired immune system that allows an attenuated virus to undergo many rounds of replication. This gives it an opportunity to mutate back to the more harmful genotype. A normal immune system would nip it in the bud, before it had much opportunity to do this. (6)

Much of the current vaccine scare started, however, with the research of Andrew Wakefield in 1998. For reference, I’d like to direct you to this paper called “Vaccines and Autism; A Tale of a Shifting Hypothesis.”(7) I found the title alone very compelling, because it does seem as though the anti-vaccination groups can’t make up their mind about how vaccines cause autism. Andrew Wakefield started it with his gastrointestinal inflammation hypothesis, but since then, people have suggested everything from ethylmercury to autoimmunity. It’s almost as though the anti-vaxxers don’t really care about the mechanism. Any mechanism will do, as long as it can be blamed on vaccines. That doesn’t mean these claims should not be investigated, but the mere fact that the anti-vaccine crowd seems intent on blaming autism on vaccines regardless of the mechanism undermines their credibility. The paper summarizes just how un-compelling the wakefield research was, and goes into depth on the many failed attempts to find any correlation to autism. It also addresses the proposed mechanisms. It’s as good a primer as any.

I honestly don’t see much point in addressing the Wakefield hypothesis, since it seems to have been roundly rejected by everyone, and really didn’t present much in the way of evidence. All he did was basically say “Hey, I found a few kids who had stomach trouble and vaccines sort of around the time they were diagnosed with autism.“ However, it’s not strange that these would happen around the same time. He didn’t even do any control treatment, to compare individuals who received no vaccine. It’s barely worth mentioning. However, the links with autism and mercury and autoimmunity are currently being discussed in the medical literature, so I will address these.

Vaccines, Autism, and Ethyl Mercury

The first claim I heard involving the link between vaccines and autism involved thimerosol, or ethyl mercury, and I don’t think that’s any coincidence. A quick search online shows that this is a pretty popular notion. At first glance, this makes some sense, because mercury is a heavy metal, and like many heavy metals, it is a neurotoxin. However, this is not proof in itself, because there are many differences between mercury poisoning and autism. For instance, mercury poisoning is strongly associated with tremors, muscle spasms, and ataxia, whereas autism is not. The difference doesn’t end there. Even the autopsied brains of autistic individuals are physically unlike those that have suffered from prenatal or postnatal mercury poisoning. For one thing, autistic brains tend to have greater than average volume, whereas mercury poisoning results in atrophy of the brain. (8) So mercury’s neurotoxicity proves very little, since that neurotoxicity doesn’t manifest itself in an autism-like manner.

Not all mercury compounds are of equal toxicity. The preservative mercury compound found in some (though not all)  (9) vaccines is thimerosol, which becomes ethyl mercury in the body. A lot of studies estimating mercury toxicity use methyl mercury.  Consequently, anti-vaccine people also cite papers describing the toxicity of methyl mercury, and then extend the same conclusions to ethyl mercury. However, whereas methyl mercury is eliminated from the blood with a half-life of about 44 days, ethyl mercury is eliminated with a half life of only about 7 days. (10) The paper cited also adds that  the highest level of blood mercury following vaccination in the children they tested was ≤8 ng/mL.

So how much is that? Well, according to the CDC (11) :

In 2000, the National Research Council of the National Academy of Sciences determined that a level of 85 micrograms per liter (µg/L) in cord blood was associated with early neurodevelopmental effects. The lower 95% confidence limit of this estimate was 58 µg/L.

This limit was set by a study using METHYL mercury, so bear in mind, it will tend to overestimate ethyl mercury toxicity. So using this limit for thimerosol is highly conservative. If we use the 95% confidence limit, it becomes even more conservative. So we can safely say that the highest level of mercury concentration observed in the study was less than a seventh of the minimal concentration that *might* be associated with neurological harm in children, and it was in the system for about a sixth of the standard time.

Still, just to be on the safe side, we may want to limit mercury exposure. It is good to know that vaccines intended for small children no longer use thimerosol. Only those vaccines that are typically administered to adults now use this preservative, which raises the safe dosage level considerably. Additionally, with the removal of Thimerosal, autism rates have continued to increase. (12) (13)

There is a paper out there claiming to show that the rate of neurological disease has fallen since thimerosal was withdrawn, by a father and son team of the last name Geier. This paper seems to disagree with pretty much all data found elsewhere, and there have been exhaustive debunkings of the paper, demonstrating how they arrived at a completely different conclusion from everyone else. These techniques include creatively “imputing” (assuming) hypothetical autism cases that would have been uncovered during a longer follow-up period.  Also, whereas other studies have measured the correlation between mercury dose in *individuals* and autism rates, the Geier study simply took the average Hg dose per person for each birth cohortand then compared just seven different cohorts to one another. So their graph has just seven points, and one of their axes is an average. They had no individual data on which people within each cohort had autism and which people got vaccines. With these eccentricities, it’s no big mystery how they arrived at such a unique conclusion.  A series of posts on Epi Wonk go into depth on this, and  the final post supplies links to three studies in California, Denmark, and Japan and showing that autism has continued to rise since thimerosal removal.  (14)

In addition to “Geier”, another name to watch out for is Tomljenovic. In one widely circulated paper, he resorts to ignoring cohort dates of birth and using different sources of data to get different results where necessary. (15) One thing you notice, actually, is that a lot of anti-vaccine studies are put out by just a handful of the same people. Not all scientific papers are equal, and a position that is being argued by a small, specific group is usually the weaker one. At the end of the day though, you really have to read a paper and have an understanding of what is actually being measured in order to know if it really proves what it claims (or what others claim) it  proves. Still, if you do ever get to researching vaccines yourself, pay attention to the names on each paper. I promise you will notice a trend if you do!

Vaccines, Autism, and Autoimmunity

Surprisingly, there is some evidence in medical literature showing possible links between vaccine-triggered autoimmunity and autism. At the very least, there is strong evidence that individuals with autistic-spectrum disorders are immunologically different, either due to environmental or genetic factors.

In particular, autistic individuals seem especially likely to have specific anti-measles antibodies, as well as elevated cytokines and antibodies targeting components of the nervous system. In this review covering the immunological factors behind autism (16), they find it plausible that both measles infections and measles vaccinations may increase the risk of autism in susceptible individuals by triggering an autoimmune response.

However, there might be other reasons that autistic individuals have unique antibodies. A hypothetical autoimmune reaction leading to autism may be dependent on certain genes being present.  HLA genes for instance, are a major factor in autoimmunity risk. These genes code for the receptors that immune cells use to detect foreign antigens, and to a large extent they also determine which autoantibodies you are likely to produce. I googled “HLA types Autism”, and interestingly, I found a paper showing that certain HLA types are also common in autistic individuals. (17)

According to this paper, the autoantibodies against nervous system components may not even be the direct cause of autism, since small amounts of auto-antibodies may be present even in healthy individuals. In this case the presence of unique antibodies in autistic individuals may have more to do with them having common HLA types than with their vaccination history. So in itself, the fact that autistic individuals appear to have peculiar antibodies is not proof positive of causation by vaccines. It would be interesting to see a study screening non-autistic individuals with the same HLA types associated with autism, to see if they had the same auto-antibodies.

Another mechanism mentioned in the review involves a “maternal-fetal immune interaction.” Basically, components of the mother’s own immune system accidentally alter the neurological development of the fetus. In this mechanism, it is the prenatal exposure to a pathogen that triggers the transfer of maternal cytokines (immune system signaling proteins) across the placental barrier. Many studies have found a high correlation between prenatal infection, and autism. (18) This mechanism would also explain the immunological peculiarities seen in autistic individuals. Additionally, this mechanism seems to have been reproduced in animal models (19)

Needless to say, the field of autism spectrum disorder etiology is a large and complex one. It really deserves its own post. If I had to sum up the current scientific view, it seems to involve many different factors, ranging from immunological causes, genetic predisposition (20) and environmental exposure to chemicals (21). Hell, in just the time it has taken me to write this post, another news story has broken claiming that elevated steroid hormones cause autism! (22)

This all makes sense, if you take into account the possibility that autistic spectrum disorders are a collection of similar disorders with separate causes.  If that’s the case, then the list of things that correlate with “autism” may be a very long one.

With current studies showing no correlation between autism and the MMR vaccine (23) (24) . There seems to be plenty of other possible causes out there without having to blame vaccines. Even if there is a correlation, current data show that it may be a very small one that is easily drowned out by other factors in epidemiological studies.

Vaccines have been linked to other autoimmune disorders as well. There does indeed seem to be a phenomenon known as ASIA  (Autoimmune/Inflammatory Syndrome Induced by Adjuvants) in which vaccination causes autoimmunity. Thus far, four disorders have been linked to this vaccination hazard. Far from being stifled by “the conspiracy”, these risks are frankly discussed on pubmed. (25) However, most of the literature out there seems to consider these risks small, and difficult to verify in epidemiological studies.  For instance, studies on an H1N1, HBV, and HPV vaccine have shown little or no increase in risk for autoimmunity. The risk is considered real, but nowhere near large enough to outweigh the collective benefits of all vaccines worldwide. (26)

Even once we accept that vaccines can play role in autoimmune disorders, and even if we include autism among them, we still cannot dismiss vaccines altogether. Vaccines may cause autoimmunity because they stimulate the immune system, but so do the infections prevented by vaccines. If the measles vaccine causes an autoimmune reaction leading to autism, for instance, then what about an actual measles infection? Some claim that vaccines may carry a greater risk of autoimmunity than normal infections, because they often use an aluminum adjuvant to increase immune response. On the other hand, natural infections can also produce a much stronger immune response than vaccines do (27) (28). So natural infections prevented by vaccines may pose an equal autoimmunity risk, if not greater. The link between viral infections and autoimmunity has been explored for some time. To quote a paper from the FASEB journal, (29)

“Others have reported epidemiologic and serologic correlations between viral infections and autoimmune diseases like multiple sclerosis (MS) , insulin-dependent diabetes mellitus (IDDM), bacterial infections, and ankylosing spondylitis (AS).”

How much might these disorders increase in an unvaccinated world? The implications of this may extend to autism risk as well. Even if we accept the most plausible link between autism and vaccines- the autoimmune mechanism- we still end up questioning whether vaccine-preventable natural infections (particularly prenatal infections) pose a greater autism risk than vaccines. If so, then some vaccines may actually reduce autism risk to the population at large! Such a conclusion was put forth by this paper, (30)

They pointed out the link between autism and congenital rubella infection. They estimated that 830 to 6225 cases of autism spectrum disorder have been prevented by the rubella vaccine from 2001 to 2010. Not to mention the prevented 8300-62,250 cases of congenital rubella syndrome. Autoimmunity can be an ugly thing, but it seems that vaccines do as much good as bad in that area.

Benefits and Cost-Benefit Analysis

This brings us to the final part of this paper; the benefits of vaccines. This is what it all comes down to; a cost-benefit analysis. Even accepting the real risks of attenuated vaccine reversion, and autoimmunity, we must ask ourselves how these compare to the diseases prevented by vaccines. Amazingly, some people claim that vaccines don’t even reduce infection rates. This is quite a claim. If you accept that the adaptive immune system exists, you must also accept that immunization is possible, in principle. If immunization is possible, then wouldn’t the pharmaceutical companies find it more profitable and less risky to use the millions of dollars spent on vaccine research on making real vaccines? That’s not even counting the money they would have to be covertly spending on cover-ups, bribes, and employees they have to pretend to need. The amount of trickery involved would be astronomically large, because there is virtually no end of sources showing that vaccines reduce infection rates. You could read them all day.

Just for example, you can see the H. Influenzae type b rate plummet in Scotland immediately following the introduction of a vaccine. (31) Anti-vaccine groups like to try and credit the decrease in disease following the introduction of vaccines to “improved sanitation”, yet the latter example involves an H. Influenzae b vaccine introduced in 1992. Perhaps they are claiming that Scotland did not discover sanitation until 1992?  The examples of successful vaccines are too numerous to be ascribed to any one coincidence. Then of course, there’s the famous example of Poliomyelitis, which decreased from 16,000 infections per year to only 12 following the introduction of the Poliomyelitis vaccine. (32) Some paranoid individuals like to point out that many of the modern polio infections are from vaccines, but considering the trade-off from 16,000 to 12, that seems a small price to pay.

Some will point out that vaccines do not guarantee 100% protection. At first glance, a protection rate of about 70% doesn’t sound all that promising. However, this misses the point entirely. Even with just 70% protection, you can wipe a virus off the map. This is because you don’t need to reduce to infection rate to zero, you just need to reduce the infection rate to below the rate at which individuals leave the infected population. By “leave the infected population” I mean either through death or recovery. If the infection rate isn’t keeping up with the rate at which the infected are dying and recovering, the disease will gradually disappear from the population. So 100% immunity isn’t even necessary.

Other benefits may include cancer reduction. The HPV vaccine, for instance, is associated with a 70% decrease in risk for cervical cancer. This is because the Human Papillomavirus itself is believed to cause about 5% of cancers worldwide! (33)

Furthermore, an estimated 15% of cancers worldwide are caused by viral infections. (34) The potential to save lives by vaccinating against these viruses- based on cancer risk alone- is therefore staggering.

So the final verdict on vaccines is still pretty favorable. Vaccines can cause infection in rare cases, although they significantly reduce the likelihood of infection overall. They can also trigger autoimmunity, and there’s a small chance that some autistic-spectrum disorders can be caused by this mechanism. However, the countless infections prevented by vaccination can also trigger autoimmunity, so it’s hard to say whether there is a net loss or gain there. Also, the mercury-autism link is just pure nonsense.

Cancer and disease prevention, however, are a clear, massive net gain. These benefits would outweigh the risks even under very conservative scenarios. The CDC has attempted to quantify the massive benefits of vaccination of young children alone, since just 1994, and they come out to over 700,000 lives, hundreds of millions of hospitalizations, and hundreds of billions of dollars. (35) Additionally, the cost of allowing a disease to return from the brink of extinction is potentially infinite, as it will accumulate with every generation that could have been spared from infection. Our children and our children’s children may one day ask why we did not eliminate some diseases when we had the chance.  Everything in life carries risks. All decisions in human society come down to weighing costs and benefits. Don’t let every little risk dissuade you from a promising technology. Try to measure the risks for yourselves, based on the best information available, and then ask if they are worth it. This path may be uncertain, but it is far better than allowing yourself to be ruled by gut feelings and fashionable philosophies. These are both poor substitutes for logic.

1)      http://www.fdareview.org/approval_process.shtml

2)      http://www.discoverymedicine.com/Michael-Dickson/2009/06/20/the-cost-of-new-drug-discovery-and-development/

3)      http://content.healthaffairs.org/content/24/3/622.full

4)      http://www.skepticalraptor.com/skepticalraptorblog.php/big-pharma-supports-antivaccine-movement-conspirac-vaccines-maybe-not/

5)      http://www.medscape.com/viewarticle/538044

6)      http://www.immunopaedia.org.za/fileadmin/pdf/Infant_poliovirus_vaccine_paralysis_10MAY12.pdf

7)      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2908388/

8)      http://pediatrics.aappublications.org/content/111/3/674.long

9)      http://www.fda.gov/biologicsbloodvaccines/safetyavailability/vaccinesafety/ucm096228

10)   http://pediatrics.aappublications.org/content/121/2/e208.long

11)   http://www.cdc.gov/biomonitoring/Mercury_FactSheet.html

12)   http://www.ncbi.nlm.nih.gov/pubmed/12949291

13)   http://www.ncbi.nlm.nih.gov/pubmed/15877763

14)   http://www.sciencebasedmedicine.org/why-the-latest-geier-geier-paper-is-not-evidence-that-mercury-in-vaccines-causes-

15)   http://leftbrainrightbrain.co.uk/2013/07/10/comment-on-do-aluminum-vaccine-adjuvants-contribute-to-the-rising-prevalence-of-autism/

16)   http://www.ncbi.nlm.nih.gov/pubmed/16512356

17)   http://www.hindawi.com/journals/aurt/2012/959073/

18)   http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068755/

19)   http://www.ncbi.nlm.nih.gov/pubmed/17913903

20)   http://www.pnas.org/content/103/45/16834.short

21)   http://www.ncbi.nlm.nih.gov/pubmed/22537663

22)   http://www.sciencedaily.com/releases/2014/06/140603092428.htm

23)   http://www.ncbi.nlm.nih.gov/pubmed/15366972

24)   http://cel.webofknowledge.com/InboundService.do?product=CEL&SID=2BEvC2fFJ1gZ28IwTLu&UT=000080812200012&SrcApp=Highwire&action=retrieve&Init=Yes&Func=Frame&SrcAuth=Highwire&customersID=Highwire&IsProductCode=Yes&mode=FullRecord

25)   http://www.ncbi.nlm.nih.gov/pubmed/20708902

26)   http://www.ima.org.il/FilesUpload/IMAJ/0/38/19310.pdf

27)   http://jcm.asm.org/content/40/5/1733.full

28)   http://www.ncbi.nlm.nih.gov/pubmed/21411604

29)   http://www.fasebj.org/content/12/13/1255.long

30)   http://www.ncbi.nlm.nih.gov/pubmed/21592401

31)   http://www.hps.scot.nhs.uk/immvax/Hib-Haemophilusinfluenzaetypeb.aspx

32)   http://www.ncbi.nlm.nih.gov/pubmed/6150330?dopt=Abstract

33)   http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2584441/

34)   http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1994798/

35)   http://www.usatoday.com/story/news/nation/2014/04/24/cdc-vaccine-benefits/8094789/

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