Proto-Antifragility

PROTO-ANTIFRAGILITY

There have been names for two starter-antifragility concepts, with two precursor applications that cover some special cases of it. These are mild aspects of antifragility and limited to the medical field. But they are a good way to start.

According to legend, Mithridates VI, king of Pontus in Asia Minor, while hiding after his father’s assassination, got himself some protection against poisoning by ingesting sub-lethal doses of toxic material in progressively larger quantities. He later incorporated the process into a complicated religious ritual. But this immunity got him in trouble a bit later as his attempt to take his own life by poisoning failed, “having fortified himself against the drugs of others.” So he had to ask for the services of an ally military commander to give him a blow with a sword.

The method named Antidotum Mithridatium, celebrated by Celsus, the ancient world’s famous doctor, had to be rather fashionable in Rome, since about a century later it brought some complication to the emperor Nero’s attempts at matricide. Nero had been obsessed with the idea of killing his mother, Agrippina, who, to make things more colorful, was Caligula’s sister (and, even more colorful, was the alleged lover of the philosopher Seneca, more on whom later). But a mother tends to know her son rather well and predict his actions, particularly when he is her only child—and Agrippina knew something about poison, as she might have used the method to kill at least one of her husbands (I said things were quite colorful). So, suspecting that Nero had a contract on her, she got herself Mithridatized against the poisons that would have been available to her son’s underlings. Like Mithridates, Agrippina eventually died by more mechanical methods as her son (supposedly) had assassins slay her, thus providing us with the small but meaningful lesson that one cannot be robust against everything. And, two thousand years later, nobody has found a method for us to get “fortified” against swords.

Let us call Mithridatization the development of tolerance to a particular substance through repeated exposure. The effect is substance-specific, rather than immunity to poisons generally. Vaccination and allergy treatment also involve exposure, but their immune mechanisms should not be equated with poison tolerance. It is not quite antifragility, still at the more modest level of robustness, but we are on our way. And we already have a hint that perhaps being deprived of poison makes us fragile and that the road to robustification starts with a modicum of harm.

Now consider a case when the poisonous substance, in some dose, makes you better off overall, one step up from robustness. Hormesis, a word coined by pharmacologists, is when a small dose of a harmful substance is actually beneficial for the organism, acting as medicine. A little bit of an otherwise offending substance, not too much, acts to benefit the organism and make it better overall as it triggers some overreaction. This was not interpreted at the time in the sense of “gains from harm” so much as “harm is dose dependent” or “medicine is dose dependent.” The interest to scientists has been in the nonlinearity of the dose-response.

Hormesis was well known by the ancients (and like the color blue was known but not expressed). But it was only in 1888 that it was first “scientifically” described (though still not given a name) by a German toxicologist, Hugo Schulz, who observed that small doses of poison stimulate the growth of yeast while larger doses cause harm. Some researchers hold that the benefits of vegetables may not be so much in what we call the “vitamins” or some other rationalizing theories (that is, ideas that seem to make sense in narrative form but have not been subjected to rigorous empirical testing), but in the following: plants protect themselves from harm and fend off predators with poisonous substances that, ingested by us in the right quantities, may stimulate our organisms—or so goes the story. Again, limited, low-dose poisoning triggers healthy benefits.

Caloric restriction has lengthened life in some laboratory-animal studies. Human longevity is harder to test—if the hypothesis is true, the subjects might outlive the researchers. But results in animals do not establish that restriction extends human life, nor are permanent restriction and intermittent fasting interchangeable. I see a possible hormetic interpretation here: some benefits might arise from responses to periods of scarcity. That remains an explanation to test, rather than proof that hunger is always beneficial.

Hormesis lost some scientific respect, interest, and practice after the 1930s because some people mistakenly associated it with homeopathy. The association was unfair, as the mechanisms are extremely different. Homeopathy relies on different principles, including treating symptoms with highly diluted preparations of substances thought to produce similar symptoms. It should not be confused with a measurable low-dose response. Homeopathy has shown little empirical backing and because of its testing methodologies belongs today to alternative medicine, while hormesis, as a phenomenon, has ample scientific evidence to back it up.

But the larger point is that we can now see that depriving systems of stressors, vital stressors, is not necessarily a good thing, and can be downright harmful.