Bharat Srinivasa, PhD, Experimental Medicine
The leading killer of humanity, and indeed of most species on earth has not been war or famine. Rather, the cause of death has been infectious disease. Infectious diseases have altered the nature of species, controlled the success or failure of organisms in a given environment, and indeed, been crucial to the evolution of a myriad of organisms itself. The bubonic plague, which ravaged medieval Europe and killed a majority of the populace, resulted in the selection of a certain group of people with genotypes that now happen to confer resistance to HIV. Such pandemics are common- more recently, the Spanish flu epidemic of 1918 resulted in over 50 million deaths the world over, and the SARS and swine flu epidemics of the past 10 years are still fresh in our minds.
Despite these recent epidemics, we have been more successful in the past few centuries in reducing infectious disease deaths, as well as preventing life long disfigurations that are characteristic of certain infections. A number of factors have contributed to this success- the establishment of sewage draining systems, the discovery of antibiotics; but the most controversial of these developments has been the discovery of vaccines.
Modern vaccines are a far cry from the first vaccines we created. Indeed, the first vaccine- Edward Jenner’s small pox vaccine was the similar looking cowpox virus isolated from the pustules of a person infected with cowpox. These early vaccines, including Pasteur’s rabies vaccines and more recently, the formalin inactivated vaccine against Respiratory Syncytial Virus have had unfortunate side effects- including life long disability and death. But the success of many other vaccines- polio, small pox and measles vaccines for example, have established the importance of these early life innoculations in preventing what would otherwise have been severely debilitating diseases in children. Unfortunately, vaccines are thought to be the victims of their own success.
The rise of the anti-vaccine movement in recent years has flummoxed researchers and vaccine policy makers. Why would parents refuse to vaccinate their infants against diseases such as polio that could cause lifelong disability? Why refuse vaccines against diseases that have previously had high mortality rates in young infants? Why not receive a vaccination that could significantly reduce the development of cancer in later years? The anti-vaccine movement was encouraged by the Wakefield paper, which correlated the Measles-Mumps-Rubella vaccine with the development of autism. Wakefield’s data could never be replicated, and investigative inquiry showed obvious financial biases in Wakefield’s data, and his papers were subsequently retracted. Despite this, the anti-vaccine movement has continued unabated, and recent outbreaks of measles and whooping cough have been linked to intentionally unvaccinated children.
Key points in the history of the anti-vaccine movement:
- Jenner’s cowpox innoculation to prevent small pox was not the first attempt at trying to stop this highly pathogenic virus. Since time immemorial, variolation, or injecting tiny doses of live small pox virus from an infected person to uninfected people was used to prevent severe disease by small pox. Lady Mary Wortley Montagu imported the concept of variolation to the UK in 1702, and despite some success, the treatment may have been as dangerous as the disease itself. In between then and 1796, when Jenner described his cowpox vaccine, a number of physicians had given cowpox to humans and successfully preventing small pox. Jenner’s treatment involved scraping the pus of a cowpox blister on a milkmaid and giving this to a young boy. Jenner then variolated the kid, and observed no disease. His vaccine had worked! Jenner was responsible for popularising vaccinations, introducing the scientific study of vaccinations, and indeed coming up with the term vaccine (vacca, latin for cow).
- Fears of vaccination date back to Jenner’s cowpox vaccine. The Anti-Vaccine Society in the UK famously published the following caricature of ” The Dangers of Cow Pock [sic]” drawn by the pre-eminent caricaturist of the time, James Gilray in 1802.
- In the 1800s, a number of laws were passed in the UK requiring compulsory vaccinations. In 1853, a law that made vaccinations compulsory in infants less than 3 months and fines for those who did not get vaccinated resulted in wide-spread riots throughout England. This led to the formation of the Anti-Vaccine League. An 1867 law resulted in vaccinations being compulsory up to the age of 14, and the Anti-Compulsory Vaccination League was formed to oppose this “infringement of personal liberty and choice”. Extremely vocal, the league’s publications inspired other movements in Europe, resulting in dramatic decreases in vaccinations and a concurrent increase in small pox. By 1898, a new law was passed which removed penalties for not vaccinating, as well as allowed certain parents who did not believe vaccination was effective to obtain a certificate of exemption.
- The anti-vaccine movement in the US arose from the movements in the UK. William Tebb, a leading anti-vaccinationist visited New York and founded the Anti-Vaccination Society of America in 1879. Over the next few years, this movement led to the formation of a number of splinter societies that were able to repeal compulsory vaccinations in a number of US states. Thus, far from being a recent phenomenon, the anti-vaccine movement can trace its origins back to the founding of the modern vaccine itself. The increase in media coverage, as well as the freedom of opinion that the Internet allows simply gives anti-vaccinationists a louder voice.
What do anti-vaccinationists fear?
The modern small pox vaccine is a far cry from the original one Jenner created. Rather than taking out the virus from pustules of people infected with cowpox, the vaccine that was used the world over was the live form of cowpox, that was used to vaccinate people. Small pox was finally eradicated in 1976. This remains, the only example where complete eradication of a virus has been achieved. Other viruses, such as polio still exist in small pockets of the world, and recent outbreaks have been linked to a lack of vaccination.
Given that the small pox vaccine was the live virus, it is inevitable that there would be some adverse reactions. While most of us would have been able to generate a strong enough immune response to the virus, those of us with immune deficiencies, or pregnant women were recommended against getting the vaccine due to its inherent side effects, which include, in those susceptible, full blown infection with cowpox.
The antigenic component of the vaccine (ie the protein or other particle derived from the virus or bacteria that tricks the immune system into responding and generating a memory immune response against the protein and thereby, the parent microbe that it was derived from) can be of various kinds: live-attenuated (live, but weakened so only replicates a little), inactivated (live, but cannot replicate), antigen alone (certain proteins from the surface of the microbe) and more recently, the DNA or RNA that encodes for certain proteins of the microbe. This list is also in order of severity of side effects to those with weakened immune responses, with live attenuated having higher risks than proteins or DNA. No new vaccine uses a live virus similar to the small pox vaccine- rather; any virus that is present is either inactivated or highly attenuated.
Like nearly all therapies, a certain level of risk is inevitable. Indeed, many of our anti-viral therapies- drugs that are given after a serious infection have similar chemical structures to our DNA and RNA building blocks, and thereby prevent viral replication by incorporating into viral RNA. A certain amount is also incorporated into our own DNA or RNA, thereby increasing the risk of cancer and/or other side effects. Other drugs work by directly activating our inflammatory response. A vaccine may just be far safer.
Components of a vaccination include an adjuvant, which helps triggering a stronger immune response, and agents such as formaldehyde (for inactivating the microbe), thiomersal (a mercury derived compound that acts as a vaccine preservative). The National Vaccine Information Centre, an anti-vaccine group with a title masquerading as a source of scientifically correct information on vaccination lists these and other ingredients of vaccines, such as bovine protein albumin, egg protein, MSG in bright red circles rather than numeric terms, thereby increasing the confusion of people looking for knowledge. For instance, the amount of mercury in the annual flu vaccine is marked by a red circle many fold bigger than the circle representing influenza antigens. What this would tell the uninformed is that far more mercury is present in vaccines than the active antigen, thereby resulting in severe disease than the flu itself.
The seasonal flu kills between 3000-49000 people in the US. On the other hand, deaths from the flu vaccine were miniscule. The Vaccine Adverse Events Reporting System (VAERS) collects adverse events after vaccination as reported by vaccinees. In the 2011-2012 year, VAERS data reported an increase in febrile seizures in infants under 2 years of age after receiving a vaccination. Febrile seizures in young infants are caused by fevers, and an increased risk after influenza infection (4-9% of young infants with influenza infection have febrile seizures). VAERS also reported upto 90 cases of Guillian-Barre syndrome (GBS). Amongst the many decades of seasonal influenza vaccinations, only the 1976 vaccine was linked with increased risk of GBS. GBS arising from influenza vaccinations are rare, and probably account for 1 in every million vaccinations, which is significantly lower than the actual epidemiology of GBS (1-2:100,000). It should be noted, that VAERS data is primarily from vaccinees themselves, which means that it could be biased much more research is needed on any of the adverse events that are noted from these data sets. The VAERS therefore could be equivalent to a wikipedia for vaccine adverse events.
The thiomersal fears arose from the fact that the preservative contains mercury-as ethyl mercury. Thiomersal is a preservative, and prevents growth of bacteria and/or mold in vaccine bottles. Most toxicity studies on mercury however were conducted with methyl mercury. Comparing ethyl and methyl mercury is as futile as comparing ethanol (which is in all of our alcoholic drinks) and methanol (which can cause blindness or death). Despite no correlation between thiomersal and side effects, the FDA has regulated that no vaccine licensed after 2001 should contain thiomersal. The use of single dose bottles (one dose per bottle) and the nasal influenza vaccine do not contain any thiomersal. Only multi dose bottles (ie many doses in one bottle, so the constant use may increase risk of microbial growth) contains small amounts of thiomersal.
Formaldehyde is another component of some vaccines. In high concentrations, formaldehyde (or formalin, the aqueous form of formaldehyde) is used to preserve body tissues. At lower concentrations, formaldehyde is used to fix cells- notable in laboratories for further experimental assays. Formaldehyde acts by crosslinking proteins, thereby preventing the virus from actively releasing its genomic contents and replicating. Formaldehyde is present in the seasonal influenza vaccine, in order to inactivate the virus and ensure it does not replicate in vaccinated people, while inducing a protective immune response. While formaldehyde is a known carcinogen, it has been shown to be essential in the synthesis of purines and pyrimidines, which form the backbone of our genomes. The level of formaldehyde in our bodies has been estimated to be 2.5 micrograms/ml of blood, which means even in the smallest of infants, the total amount of formaldehyde is more than that present in vaccine formulations (which at most, is 0.1mg)
At times, the level of misinformation is astronomical. Most information on vaccines and vaccine safety comes from the primary care physicians, and the case for vaccines isn’t helped if the physician is Dr Robert Sears, America’s best known pediatrician. Rather than saying vaccines are bad, Sears claims that the vaccination schedule in infants, as proposed by the American Academy of Pediatricians and the CDC is wrong and crowds the infant with a host of vaccines. Sears proposes an alternate schedule that relies on infants being vaccinated multiple times over their first 5 years of birth rather than being vaccinated early on, which is when a majority of infections occur due to the immaturity of the immune response. Sears goes further in his best selling book, “The Vaccine book: Making the Right Decision for your Child”, and states that parents should hide their infants in the herd; ie rather than vaccinate their children and risk vaccine-related diseases, parents should hide in the herd of vaccinated infants, so that the unvaccinated kids don’t contract any disease. This is flawed on many levels: While there is truth to herd immunity, delaying vaccinations (as he proposes) as well as informing people of the hiding tactic prevents parents from discussing or understanding the risks it entails for kids. If many of the herd are unvaccinated, but continue to act like they are, the levels of vaccine preventable illnesses will certainly rise since herd immunity has not significantly thinned. Sears also comes off as condescending; he claims he alone has understood the true nature of vaccinations, that the vast legions of medical students and doctors don’t understand the risks of early life vaccinations. It doesn’t help that Dr Sears is an engaging personality, and appearing on the Oprah show can definitely boost one’s perception in the public’s eyes, even if the thoughts are scientifically wrong and potentially dangerous.
Another issue that arises out of the anti-vaccinationists camp is that “Natural infection is better than vaccination”. A few chickenpox parties have been hosted through Facebook, where uninfected kids are allowed to interact with infected kids so that natural immunity may occur. Chicken pox is mild enough for kids, so the infection is cleared. However, chicken pox can cause severe infections in pregnant mothers and is highly dangerous for the developing fetus. Additionally, the body never really clears the chicken pox virus- Shingles, the adult form of chicken pox arises when the virus reactivates, following treatments for cancer or immunosuppression, or simply when the immune response starts to weaken as people age. Additionally, chicken pox in adults is more dangerous than an infection in children, and can lead to severe complications such as pneumonia, hepatitis and secondary bacterial infections.
It is a sad state of affairs that people trust celebrities such as Jenna McCarthy, Rob Schneider and Jim Carrey on the dangers of vaccines rather than the huge amount of scientific evidence that exists on vaccine safety. The anti-vaccine movement is not restricted to the US alone- although polio has been eradicated in the US, it still exists in a number of countries because of vaccine fears of a different kind- that the vaccine is secretly a sterility measure. This utterly ridiculous fear recently resulted in the death of 16 UN appointed aid workers in Pakistan, a move that has been linked to the Pakistani Taliban. Their crime? Giving the polio vaccine to poor children. There are other dangerous myths about vaccines- for instance that HIV arose out of the monkey cells used for to create the polio vaccine for instance.
It is unfortunate that these anti-vaccinationist movements have stronger media strategies than that of the pro-vaccine movement. Jenna McCarthy and Dr Sears have been on Oprah, and the NVIC recently put up public billboards extolling the dangers of vaccination. I’m not saying that there should be a war- that pro-vaccinationists should take to the streets and rally. Rather, ensuring that the right information reaches the ears of the people directly would be a good place to start. Government regulations that ensure compulsory vaccinations could be another step- some US states have made vaccination exemptions harder but there are still long ways to go. Perhaps there is a need for public debate on the importance of vaccines; for vaccine scientists and doctors to discuss the benefits of vaccine directly to the people rather than be condescending in their approach. In the 1800s, after small pox vaccination levels dropped in certain parts of Europe, a new wave of small pox rose that resulted in a dramatic increase in the number of vaccinations. Vaccinations then stayed high until small pox was eradicated over the 20th century. It is possible that there are people who have never seen polio or measles, and thus do not know of its life-altering disability or severity. Similarly, influenza is currently seen as a mild infection that leaves you in bed for a week at the most. Most people hardly know of how severe influenza epidemics can be- claiming that the 2009 outbreak was an “epidemic” may have been overkill by head honchos at WHO, but their fears arose from the greatest epidemic in recent times- and one that most people hardly know about.
The Spanish flu of 1918. In the midst of the first world war, an influenza epidemic took hold of the world and killed over 50 million people the world over- more than the number of people that had been killed in all the wars of the past century. Populations were ravaged, entire communities decimated, and entire cities becoming ghost towns. Imagine what these people would have given for a vaccine against that pathogen.
The above example was not given to scare people into getting any vaccines- rather, the sole purpose was to show that infections that we may laugh at, that we believe are mild inconveniences are only so because their worst has past back in our evolution.
The current anti-vaccination movement is dangerous if it continues unabated. Already, there is an increase in vaccine-preventable disease outbreaks in a number of countries across the world. In a way, perhaps these small outbreaks may goad policy makers to ensure mandatory vaccinations for all, but at what cost?
Or maybe it is time for war. To ensure that the anti-vaccinationist movement is stopped. We need billboards. We need celebrities. Maybe we need a Justin Bieber to convince the world that vaccines are necessary- that the benefits far outweigh the risks.
Wolfe RM and Sharp LK. BMJ, 2002. For the history of the anti-vaccine movement.
Offit PA and Jew RK. Pediatrics, 2003. A summary of the components of vaccines and their uses.
Offit PA and Moser CA. Pediatrics, 2009. An article countering Dr Sears alternative vaccine schedule.