One basic principle of toxicology is that the dose makes the poison. This means that a substance has observable adverse effects in the body only once a certain dose is achieved. This not only applies to substances that are widely considered “harmful”, but also to substances that are generally considered “safe.”
For example, water is a molecule that is vital to the existence of life, yet it can cause serious problems if large quantities are consumed within a short period of time. While it is generally considered to be the least toxic chemical compound, it is possible to drink enough water such that the normal balance of electrolytes in the body is thrown off, which in rare cases can lead to death. Cases of water intoxication have been recorded in marathon runners as well as in participants of water drinking contests.
This may seem like an extreme example, because it is. However, there are plenty of other examples to illustrate this concept:
- Snake venom can be toxic and lethal, however there is a dose below which there is no detectable toxic effect
- Drugs such as acetaminophen and ibuprofen are usually benign when taken as directed but can cause serious harm in large quantities
- Acetic acid can cause severe burns, but we regularly consume smaller, harmless doses in vinegar
- Oxalic acid is naturally found in vegetables, including broccoli, garlic, beets, onions, carrots, celery, cucumbers, peas, tomatoes, and potatoes, yet in larger doses it causes a variety of problems
- Nicotine, a drug found in cigarettes, is found in small quantities in plants such as tomatoes, eggplants and peppers
- Vitamin A is an essential nutrient, yet large quantities of it can cause liver damage
- Our bodies require magnesium, however large quantities can lead to diarrhea and even death
- Consumption of alcohol in large quantities can lead to alcohol poisoning, while much smaller amounts cannot
- Solanine is a compound found naturally in potatoes, apples, blueberries, bell peppers and tomatoes, yet in large quantities it can cause gastrointestinal symptoms, hallucinations, paralysis, and death
Anti-vaxxers claim that certain substances have no safe level of exposure, even though this violates basic toxicology. It is not enough to say that a substance is toxic. The question that matters is “at what dose are adverse events observed?”
Thankfully, scientific studies can answer this question. Animal studies can be performed to measure the lethal dose and toxicity of substances. Researchers can measure the LD50 (a measure of acute toxicity) which is also known as the “median lethal dose.” This is the dose of a given substance that is required to kill 50% of the test population. The lower the LD50, the higher the toxicity.
Another quantity is the “no-observed-adverse-effect-level,” or the NOAEL, which is the highest studied dose at which no adverse effects were observed in the test population. For example, if researchers were studying substance X and divided animals into four groups each receiving different doses, say 25, 50, 100 and 200 milligrams (mg), and adverse effects were observed only in the 200 mg group, the NOAEL for substance X would be 100 mg.
Scientists can also study large human populations to determine whether people exposed to a given substance experience more adverse effects compared to those that have not been exposed to it, or they can look for correlations that may be indicative of adverse events.
Chemistry is Important
Elemental (pure) sodium will explode when it comes into contact with water. Chlorine can be used to create a biological weapon and it can also be used to clean your swimming pool. Intuitively, we might be tempted to demonize any compound that contains one of these molecules, but basic chemistry shows that this fear is unfounded. Sodium and chlorine combine to form sodium chloride, otherwise known as table salt – a substance that does not produce a volatile explosion in water, does not serve as a chemical weapon or effective pool water cleaner, and has different effects on the body compared to pure sodium or chlorine.
Basic principles of chemistry tell us that it is erroneous to characterize a compound as dangerous based on the properties of its constituent molecules.
Thimerosal in Vaccines
In the late 19th and early 20th centuries, bacterial contamination in vaccines was a serious problem for health professionals. Vaccines that were delivered in multi-dose vials were sporadically prone to bacterial contamination resulting from multiple uses of the same vial. This contamination was less of a problem with single-dose vials, however the disadvantage of single-dose vials is that they are more costly to produce compared to multi dose vials.
In 1916, a tainted batch of typhoid vaccines caused 68 severe reactions and 4 deaths in South Carolina. In 1928, 12 children died after being administered a diphtheria vaccine that was contaminated.
Health professionals and researchers sought to fix this problem of bacterial contamination by adding a substance called a germicide to the vaccines. I won’t go into the finer details here, but the end result was that they discovered that ethylmercury (the principle ingredient of thimerosal) was a very effective germicide and that it could be administered in high doses (up to 20 mg per kg of body weight) without any adverse effects. Thus, beginning in the 1930’s, thimerosal was added to vaccines to prevent this bacterial contamination and save lives.
Why Fear Mercury?
Mercury is widely considered to be dangerous for humans – and with good reason. The Minamata Bay incident in Japan in the 1950’s is a good example of how mercury poisoning can be frightening and even deadly. The Chisso Corporation had a factory in the town of Minamata that produced acetaldehyde, a chemical used to make plastics. For many years, the company dumped its waste water into Minamata Bay. Eventually, there were stories of cats “dancing” and dying in the street, and strange symptoms soon appeared in humans – which in some cases proved to be fatal. Scientists eventually traced the cause of these symptoms to methylmercury poisoning. It turns out that significant quantities of methylmercury were being dumped into the bay by the Chisso Corporation. Unfortunately, at that time, seafood from the bay was the community’s primary source of protein.
Today, human exposure to methylmercury is achieved via consumption of fish and other aquatic species. Methylmercury is not efficiently excreted (eliminated) from the body and it therefore tends to accumulate up the food chain because it remains absorbed by tissues for a significant period of time.
Mercury and Autism?
Concern about thimerosal in vaccines began to take hold in the late 90’s, around the time Andrew Wakefield published his study raising concerns about the MMR vaccine. (Ironically, the MMR vaccine does not and has never contained thimerosal.) After many scientific studies showed that there was no link between autism and the MMR vaccine, anti-vaxxers then committed the informal fallacy of moving the goal posts by turning their attention to thimerosal.
In the anti-vaxxers’ eyes, thimerosal in vaccines was causing autism. This idea was championed by journalist David Kirby in his book Evidence of Harm, and by celebrities such as Robert F.Kennedy Jr. and Jim Carrey.
Problems with their Argument
Our intuition might tell us that it is reasonable to be fearful of thimerosal in vaccines. Is this true? No, here’s why.
First, we must go back to our discussion above which explained that chemicals with different structures behave differently. Readers with a keen eye (or those already familiar with this topic) will have noticed that in discussing mercury toxicity, I made reference to methylmercury, while I described thimerosal as containing ethylmercury. The difference is important and cannot be overstated. Somewhat similar to my example of sodium and chlorine behaving differently from sodium chloride, it is true that methylmercury and ethylmercury behave quite differently. Methylmercury, found in seafood, is absorbed by the body’s tissues for quite some time, while ethylmercury is efficiently eliminated from the body over a short period of time. Therefore, it is wrong to speak of methylmercury (found in seafood) and assume that its effects will be the same as that of ethylmercury (found in vaccines). Anyone who does this is demonstrating a lack of knowledge of basic chemistry. (This is also similar to methanol vs. ethanol: methanol is unfit for consumption, while ethanol in wine is enjoyed safely by many.)
Second, consider the other basic principle I covered earlier: the dose makes the poison. Anti-vaxxers may argue that the differences between methyl and ethyl mercury don’t matter, and that exposure to any dose of mercury is toxic. Of course, we know this is not true as this argument violates a basic principle of toxicology.
But what if ethylmercury is toxic at the dose given in vaccines? To support this assertion, someone once sent me a study showing that thimerosal administered to mice can cause autoimmune problems. Now that we know that the dose makes the poison, a perfectly reasonable and rational question is: what dose of thimerosal was administered to the mice? How many vaccines must a human receive to achieve a dose equivalent to that given in the study?
The lowest dose given to the mice that produced adverse effects was 147 micrograms per kg of body weight, per day. Doing some math, we can determine that to get the equivalent dose in a 150 lb human, we would need to administer approximately 10 mg of thimerosal. The vaccine with the highest dose of thimerosal is currently the flu shot, which comes in at 0.025 mg of thimerosal per vaccine dose. A 150 lb human would need to receive 400 flu shots to achieve this dose.
Further, we must account for the fact that ethylmercury is excreted by the body. Therefore, the span of time over which the vaccines are administered matters as well. Given that this dose of thimerosal was administered to mice over 70 days, the 400 vaccines for a 150 lb human would also have to be administered within a span of 70 days. In reality, childhood vaccines are spread out over many years. For example, the publicly funded vaccine schedule in the province of Ontario recommends 18 vaccines staggered over several years of childhood.
The two paragraphs above don’t even take into account two important points: many vaccines don’t contain thimerosal, and observations made in animals are not directly translatable to humans. These points aside, using this mouse study to argue that thimerosal is toxic is akin to arguing that a cup of water is toxic because drinking 24 cups of water at once can kill you. (The LD50 for water is roughly 6 litres)
What About Humans?
If thimerosal was somehow connected to the rise in incidence of autism, then we would expect autism rates to go down if the dose of thimerosal given to children were reduced. This occurred in 2001 in the United States when the CDC removed thimerosal from the childhood vaccination schedule. Proponents of the thimerosal-autism connection, such as David Kirby, predicted that the incidence of autism would plummet. They were wrong, as autism rates continued to rise even after the removal of thimerosal. California passed a law in 2006 removing thimerosal from all of their vaccines, yet the state’s autism rates continued to rise.
Epidemiological studies in humans have extensively studied the alleged connection between thimerosal and autism. A review of the scientific evidence published in 2010 concluded:
[…] studies have consistently failed to identify a cause-effect relationship between thimerosal and autism. In addition, the prevalence of autism has increased despite a decrease in the thimerosal content of vaccines; […] Despite failure to demonstrate an association, certain states continue to mandate that vaccines given to children contain no more than trace amounts of thimerosal. Epidemiologic studies continue to provide evidence that there is no association between thimerosal exposure and autism.
Of course, these findings should not come as a surprise given all of the science that has been done to investigate the toxicity of thimerosal.
Despite the wealth of epidemiological studies and thimerosal’s removal from most vaccines having no effect on autism rates, anti vaccine proponents and celebrities continue to stoke a fire that should have been extinguished over 10 years ago.
The case of thimerosal is a good example of why basic tenets and evidence from epidemiology, toxicology and chemistry need to be effectively communicated to the public.