A Question of Method

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By: Amanda Abunimeh

One of the reasons MSG toxicity has been contested in the scientific community is because there are so many different methods researchers can choose from when conducting their experiments. Historically, a popular method in toxicology research has involved injecting mice (or other test animals) with mega-doses of MSG, and then observing the effects. Apparently, someone thought this was a good way to model MSG consumption in humans. The problem is, I sincerely doubt that any human has spent an afternoon shooting MSG into their arm– and if anyone has, I feel like it’s probably time for an important chat with their dealer.

You might be wondering how this is okay, but here’s the thing– when science is talked about in the news or in popular discourse, people have a funny way of leaving out details. It suddenly becomes all about sensationalist headlines (ie. MSG is toxic!!) pulled from the title, the abstract, or a sentence in the results sections, and methodology tends to get left out. Because society values research that produces statistically significant findings, researchers are more likely to use methods that produce clear, manageable results. However, the question remains: just because humans are not self-injecting huge amounts of MSG, are the results of these experiments necessarily invalid?

Here’s one little example from a vast literature. In July 1972, Ghadimi and Kumar published an editorial in the American Journal of Clinical Nutrition entitled “Current status of monosodium glutamate.” The two doctors argued that the claims of MSG causing permanent damage to the central nervous system were largely unfounded. They cited a 1969 study that found MSG caused a burning sensation when injected in the arms of two patients wearing pressure cuffs. Ghadimi and Kumar pointed out that the burning sensation did not extend up the arm until the cuffs were removed, which would indicate that the sensation was actually a product of the peripheral nervous system [all of the nerves in the body, excluding the brain and spinal cord]. In other words, the MSG was a localized nervous reaction, and was not sending signals to the spine or the brain. Like Ghadimi and Kumar, I found it difficult to imagine how MSG injection could result in permanent brain damage, if the compound was only interacting with the nerves surrounding the injection site.

They also reviewed about nine reports of MSG potentially causing “irreversible damage” to the central nervous system, and found that most of the nine reports used doses of MSG that were about 20 times higher than what an average person would normally consume in one sitting. Additionally, in most of the studies, the MSG was administered “parenterally,” which is science-speak for routes of administration other than oral ingestion. You can use your imagination with that one; however, in these particular studies, the MSG was being injected. Ghadimi and Kumar argued that the combination of intravenous administration and uber-high loading doses was akin to “judging the effect of a breeze by examining the havoc caused by a hurricane.”

In other words, methods that could be perceived as extreme are bound to lead to extreme results; the difference between normal MSG consumption and injecting megadoses is so astounding that they may as well be considered different processes entirely. One does not model the other.

About one year after Ghadimi and Kumar’s editorial came out, in July of 1973, John W. Olney published a counterargument in the same journal. Not coincidentally, Olney had been the first researcher to find that MSG, when injected, can cause permanent brain lesions in mice in 1969. In his 1973 letter to the editor, Olney argued that Ghadimi and Kumar were too focused on the symptoms related to Chinese Restaurant Syndrome, which occurs in adults (and was also the reason that MSG came under criticism in 1968). According to Olney, Ghadimi and Kumar failed to recognize that the reports of MSG-induced brain damage were not referring to adults, but infants– specifically, the developing brains of immature animals. Olney’s study in particular found that MSG injection in newborn mice resulted in brain lesions, which ultimately caused stunted development, obesity, and female infertility in adults. Although he did not give a reason for why we should accept intravenous injection as a good model for potential toxicity resulting from routine oral consumption, Olney does claim that there had in fact been studies done to determine the lowest oral dose required to produce lesions in an infant brain (0.5 g/kg in an infant mouse). The study in question, interestingly enough, was also done by none other than Olney himself. It was at this point in the letter that I began to wonder about Olney’s motivation; was he genuinely concerned about Ghadimi and Kumar’s neglect of the potential effects of MSG on infants, or was he simply trying to defend his own work?

The letter continued to pick apart their argument, study by study, until Olney concluded with a final punch: he suggested that Ghadimi and his colleagues might be too ready to dismiss the potentially dangerous effects of MSG on infants, because if proven to be true, these harmful effects would threaten their own research on the use of MSG as an appetite stimulant for infants with Lesch-Nyhan disease [a genetic disorder that affects young children, resulting in a range of developmental and behavioral disabilities]. So do all scientists have  personal agendas? Apparently, Ghadimi and Kumar had an interest in MSG’s pharmacological activity as well. While their motives might sound a little more heroic than Olney’s (after all, it’s for the children), their Lesch-Nyhan treatment would never be accepted if it turned out that MSG caused permanent brain damage in infants. And if we’re being honest, actively attempting to discredit research that could demonstrate particular vulnerability to MSG consumption in infants (the basis of their experimental treatment) is not exactly “hero” behavior– we might even call it unethical.

So what can we take away from this debate? We learned that each party had something important to gain from winning the argument, and that these personal, career-driven agendas could definitely have contributed to biased conclusions. Was Olney’s suggestion that MSG affected infants differently than adults trustworthy, if his intentions were to defend his own work? What’s the difference between self-promotion, as a scientist, and promotion of sound science? Even if Ghadimi and Kumar’s argument against intravenous MSG injection makes sense to us, is it ethical for them to have made the argument in the first place, if they were actually trying to undercut a threat to their own research?

The point is, contesting results aren’t as simple as correct science versus wrong science. This debate is the perfect example of a situation in which the “science”– supposedly unbiased, black-and-white facts– can’t be separated from the conflicting personal agendas and professional rivalries. This is one illustration of a long historical pattern: very rarely do we get science without the– for lack of a better term– baggage.

When I first stumbled across this 1972 debate, I thought I had found answers to my questions about methodology. After peeling back the layers, however, I learned that what I had actually discovered was validation– validation, and more questions. I still wonder about the ideal study design, the one that would produce results most applicable to real life. In the case of MSG’s alleged toxicity, I start with the following questions. First, can intravenous injection really be considered a legitimate method of administration of MSG? Second, what constitutes a realistic dose? Unfortunately, questions like these– the ones the Ghadimi and Kumar asked– simply give rise to more questions. Are animals really an accurate model for humans? If so, which ones? Should we, like Olney, be paying attention to the effects of MSG on infants rather than adults? Can we really find the answer to any of these questions, if the institutions we trust to answer them can’t separate the science from the baggage?

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