Pundita asked for my comments on this post in which she examines a web article in which the author puts forward the theory that there really was no flu epidemic of 1918 and, rather, it was treating flu with aspirin, reducing the fevers of the stricken and allowing the disease to take fatal hold, which caused the great loss of life. It strikes me as a case of post hoc propter hoc.
Aspirin, is of course, the original wonder-drug. The idea of using salicylic acid (extracted from willow bark) as medicine wasn’t new. The Egyptians had done so almost 3,000 years ago. And the pure chemical had been known and used since the 1830’s. But I believe the Bayer Company’s account of German chemist Felix Hoffmann’s acetylating salicylic acid to make it gentler on the stomach and creating acetyl salicylic acid, christened “aspirin” by the commerce-savvy Bayer Company.
Two events that happened close upon each other served to fix aspirin in the public mind: the end of the Great War, making the German Bayer Company’s product politically acceptable in the United States and the United Kingdom and the Flu Epidemic. Aspirin treated the fever and ache symptoms of the flu like no other drug and it was the flu that gave aspirin its reputation.
Interestingly, the mechanism by which aspirin worked was unknown until the late 1960’s when pharmacologist John Vane of the Royal College of Surgeons in London discovered that aspirin stopped the body’s cells from manufacturing an important subclass of eicosanoids called prostaglandins by destroying a single cyclooxygenase enzyme, the enzyme which controls the manufacture of all prostaglandins. One molecule of aspirin destroys one molecule of cyclooxygenase enzyme.
Prostaglandins have all sorts of functions in the body from regulating the widening and narrowing of blood vessels, blood clotting, and temperature regulation. Oh, and Vane won part of the Nobel Prize for Medicine in 1982 for his discovery.
Back to the flu.
Did the use of aspirin cause what would otherwise have been a self-limiting epidemic into a fatal pandemic? The more virulent the disease, the greater the tendency for it to be self-limiting for a very simple reason: it kills the host and thereby limits the host’s ability to transmit the disease to other victims. And it very well may be true that prolonged body temperature over 105°F may kill the flu virus. IIRC the optimal temperature for propagating flu viruses is 33°C-36°C which means normal body temperature (actually 98.2°F) is already sub-optimal for flu so reducing somebody’s fever a little may render them more slightly more hospitable to the virus but probably won’t make them any sicker. I suspect that’s why the consensus view among physicians seems to be to reduce temperature.
It seems to me there are several ways we could test the hypothesis. Were there higher rates of fatality in areas where aspirin sales were higher? Were there higher rates of fatality in areas where the ambient temperature was lower (aspirin isn’t the only way to lower body temperature)?
So my conclusion is a resounding “Maybe” (but I doubt it).
There were rumors at the time of the epidemic that the flu was the result of chemical warfare by the Germans. One of the rumors was that Bayer Aspirin was used to transmit the flu. This story sounds like a modern version of that rumor. I don’t have any medical training but it doesn’t take any special knowledge to find the factual errors in “Murder in the Medicine Cabinet”.
Dave, thanks for taking this one on. One of the many things I questioned about the article is the author’s contention that modern doctors don’t understand the mechanism of fever and flu virus. Just on intuition it seems to me that an extended period carrying a very high temperature can be a killer for many people, which is probably the medical rationale for applying anti-febral measures. The part that worried me is the general observation that aspirin and any anti-fever “cold” medication masks the onset of a viral infection. I’d never thought of that before. The point can have very serious implications with regard to trying to nip an epidemic in the bud. If the author’s observation holds true, maybe people should be educated not to routinely self-medicate with aspirin-based products, particularly during flu season, and particularly if they’re using the product simply as an anti-inflammatory medication. Beyond the author’s hypothesis about the 1918 pandemic (which strikes me as very hard to prove even if one accepts his basic idea) there is the simple observation that fever is a powerful immune system weapon. We overlook that, in this era when we self-medicate and “keep going” rather than allow ourselves to be bedridden for a day or two.
The link between aspirin and Reye’s syndrome is well established. That’s why physicians don’t recommend aspirin for flu-like illnesses and chickenpox, etc, anymore. Reye’s syndrome is often fatal. It is also true that the body is better able to fight many microbes with the assistance of a higher body temperature. The ancient use of saunas, sweat lodges, steam tents, hot soaks, etc may have a primitive use of that concept. Piling on the blankets until the “fever broke” was another approach.
Some fevers are damaging, for instance above 104 degrees F. Neural tissue can be permanently damaged by prolonged, very high fevers. Febrile seizures may occur at lower temperatures, and preventing such seizures is a common reason for using tylenol or ibuprofen in children with temperatures above 102 F.
(I had already typed out this comment before visiting here and seeing the comment added by Ron. I almost fell out of my chair when I read his observations.
For heaven’s sake, shouldn’t the medical community and even the FDA and insurance companies issue more warnings about aspirin use? What Ron is saying isn’t generally known. One would think that doctors and maybe the FDA would give more warnings about aspirin use!)
Dave — this morning, after rereading your post, mine and the Marshall Smith article, I was again struck by one point:
Smith is saying is that a body temperature of only F 101 stops the flu virus from dividing and replicating into millions of copies — a process that can easily overwhelm the immune system’s defenses.
If that statement holds up, it means that an aspirin user can easily pay with death for very temporary relief from a mild fever!
At the least it would mean that aspirin use should be weighed very carefully and with input from a physician.
Regarding Mary Beth’s comments: I hadn’t known about the scare stories regarding Bayer Aspirin during the 1918-19 pandemic but that makes sense. It’s likely that any product associated with Germany would have been suspect in America during that era.
So her comment, along with your questions, raises more questions about Smith’s ‘hypothesis,’ if it can be called that. Maybe there were several converging factors creating the large number of deaths from Spanish Flu — a kind of perfect storm of factors.
Maybe aspirin use was one factor (in Europe?), but I note that Smith’s article was written before Spanish Flu was recreated in the lab and the results published. From the researchers’ account, that is a horribly lethal form of bird flu — a real superkiller.
So I still have a hard time buying Smith’s hypothesis enough to investigate it. But his idea about the Spanish Flu is only one part of what he was writing about — and to my mind, not the most important part.
This morning I again asked myself: Would I be willing to give up aspirin if I saw an epidemic coming America’s way? Right now the answer is: Yup, if Smith’s medical facts hold up.
So I rewrote my post, in the effort to make it clearer why I was willing to take a flyer on Smith’s article, which as you know does not contain so much as one footnote.
An opinion from a MD about Smith’s presented facts is sorely needed at this stage. And if I am going to pursue this story, I will have to tangle with a medical encyclopedia in the effort to check Smith’s description of fever and flu virus. I note you already caught him in one error.
Yet this is one story that won’t let me go. There is a common-sense aspect to Smiths’ basic observations. Recall the old adage, “Feed a fever, starve a cold.”
We’ve come to greatly fear fever during the modern era, when we’re so busy we can’t stand the thought of being laid up even a day with fever. Only more digging about Smith’s comments will turn up whether that attitude is okay, or very bad news for the human immune system.
Because of Reye’s syndrome, there have been warnings against using aspirin or other salicylate containing medicines when a fever is present (especially for children and teenagers) for a couple of decades. These drugs include Alka-Seltzer, Pepto-Bismal and Kaopectate. There should be a warning on the label or in the package but you can also look at the ingredients for anything with “*salicyl*” as part of its name. Other non-steroidal analgesics (acetaminophen, naproxen, and ibuprofen) don’t have the same risk and most medications for children have changed their formulas substituting these for the aspirin.
Most flus begin as an avian flu. The general belief is that the avian flu is “mixed” in a secondary host (frequently pigs) with one that humans can catch. The pig would have two types of the virus in its system and genetic parts of one are swapped with parts of another. People then catch the virus from their domesticated animals. These flus are less dangerous because while people are not immune to new strains, their bodies have a better chance of fighting the virus because of parts that are similar to previous strains. About every thirty years or so a strain comes out that is unlike others and causes a pandemic such as the Spanish flu. Research is being done to see if these flus skip the secondary host and are transmitted directly from birds to humans.
Deaths from the Spanish flu probably had nothing to do with aspirin or any attempts to reduce fever. It was a new strain rather than a mutation and people’s bodies produced an exagerated immune response that is called a “cytokine storm” resulting in a build-up of T-cells and fluids in the lungs. It happened quickly and to those with the strongest immune systems which is why so many people in the 20 – 40 year age group died.
If what MB says is true that those with the strongest immune system suffered most from the cytokine storm and died is it a mistake to “shotgun immunize” against avian flu like the Finns are doing? If a vaccine sensitizes and exaggerates an immune response against a particular virus like the 1918 flu is it protective or exacerbative?