Hormesis is the ability of organisms to become stronger when exposed to low-dose stress. Is hormesis a basic principle of biology — or is it merely a strange but unimportant quirk of nature that only applies in exceptional circumstances?

Nassim Nicholas Taleb–the options trader turned philosopher–is intrigued by hormesis, and sees it as but one example of a much broader phenomenon: a fundamental principle he calls “antifragility”. The principle of antifragility applies not just to biology–but to sociology, economics, and perhaps even physics. Taleb has been developing this idea for a number of years. Antifragility made a subdued appearance in his 2007 blockbuster work, The Black Swan, a guide to dealing with unpredictable yet momentously consequential events in our increasingly volatile world. Taleb has now more fully developed the concept of antifragility in his most recent book, Antifragile: Things That Gain from Disorder.

The antifragile is the antithesis of the fragile. You might suppose that the opposite of “fragile” is something like “robust” — something that resists change. But Taleb points out that that would be the wrong answer. A fragile thing – a package of wine glasses, perhaps — is easily broken when subjected to a stressor, such as being dropped. Something robust is merely resistant to breakage. But an antifragile object actually benefits by being subjected to stress. Taleb conjures up an image of the fragile as an object we would ship in a box marked “Handle with Care”; by contrast, a box holding the antifragile would be labelled “Please Mishandle”

At first, this seems to be a tease. Are there really such antifragile things? Yes, indeed; the world is full of them, including you and me. And there are steps we can take to become ever more antifragile.

Humans, and all living organisms for that matter, are antifragile — at least to a point. Our bones and muscles get stronger when subjected to the stresses of walking and lifting things — and they wither when they go unused. Readers of this blog will instantly recognize bone and muscle development as examples of hormesis. So is antifragility the same thing as hormesis — or is it something more?

Disorder. To help us answer that question, Taleb asks us to conceptualize “stress” as but one manifestation of the more general concept of “disorder”. The physical and biological universe is a stage on which the forces of order and disorder compete and play out their drama. In the long run, we know from the second law of thermodynamics that entropy — disorder — will always increase, at least in closed systems. There are of course local skirmishes that fight the trend — Life on Earth being one such notable exception, representing an open local system that feeds off of the entropy of the larger system. According to Taleb, disorder can have a number of equivalencies:

stress

time

change

volatility

debt

That which suffers when subjected to any of these forms of disorder is fragile. That which is fragile does not age well or stand the test of time, and it is extinguished during times of increased volatility.

The antifragile is that which actually gains from any of these forms of disorder.

So what real things are antifragile? Beyond living organisms, Taleb gives a number of plausible examples:

cities

economies

biological species

books and ideas

Smaller units tend to be more fragile than the larger, more complex systems of which they are part. For example, individual cells die off, while the organism of which they are a part adapts and persists. Individual people are more fragile than families, organizations or societies. Firms–for example restaurants–can go out of business easily, while the restaurant sector of a city or country persists and even improves after an economic downturn. Dynamic cities are more anti-fragile than firms, and competitive economies even more so. These larger economic units develop and continue to satisfy economic needs despite — or because of — the creative destruction that puts individual firms out of business.

Antifragility is not just of theoretical interest. It has great practicality. Not all individuals, organizations or societies are equally antifragile. If an entity can become more antifragile, it will become better able to withstand the stresses and insults of time. To the extent that we live in a time of increasing change, volatility or disorder, this is a discussion worth having!

Interpretation of hormesis. The prototypical model of antifragility, according to Taleb, is not hormesis. Somewhat surprisingly, in Antifragile he downgrades hormesis and similar phenomena such as tolerization and inoculation (“mithridization”) to a kind of “proto-antifragility”

Mithridization and hormesis are just very weak forms of antifragility, with limited gains from volatility, accident, or harm and a certain reversal of the protective or beneficial effect beyond a certain dosage. Hormesis likes only a little bit of disorder, or rather, needs a little bit of it. They are mostly interesting insofar as their deprivation is harmful, something we don’t get intuitively–our minds cannot easily understand the complicated responses (we think linearly, and these dose-dependent responses are nonlinear). Our linear minds do not like nuances and reduce the information to the binary “harmful” or “helpful”. (Antifragile, p. 66)

What then is a bona fide example of antifragility? Taleb’s answer: evolution.

There is a different, stronger variety of antifragility linked to evolution that is beyond hormesis–actually very different from hormesis; it is even its opposite. It can be described as hormesis–getting stronger under harm–if we look from the outside, not from the inside. This other variety of antifragility is evolutionary, and operates at the informational level–genes are information. Unlike with hormesis, the unit does not get stronger in response to stress; it dies. But it accomplishes a transfer of benefits; other units survive–and those that survive have attributes that improve the collective of units…So the antifragility of concern here is not so much that of the organisms, inherently weak, but rather that of their genetic code, which can survive them…In fact the most interesting aspect of evolution is that it only works because of its antifragility; it is in love with stressiors, randomness, uncertainty and disorder–while individual organisms are relatively fragile, the gene pool takes advantage of shocks to enhance its fitness… So, in a way, while hormesis corresponds to situations by which the individual organism benefits from direct harm to itself, evolution occurs when harm makes the individual organism perish and the benefits are transferred to others, the surviving ones, and future generations. (Antifragile, pp. 66-70).

This goes back to Taleb’s thinking about the hierarchical structure of antifragility, where the smaller subunits are fragile and the larger systems are more antifragile. His key point here is that whereas most of the smaller units “die off” and don’t survive the stress, there is a “transfer of benefits” or heritable information from the surviving stronger units to the system. In biology, this happens by the replication and spread of surviving genes throughout the species, to improve the survival of the species. In economies, while many firms fail or don’t thrive, the few successful ones grow and their product designs or business models are copied and dispersed. Hence, it is the system, not the unit, that is antifragile. The system evolves to get better by selecting the features of the most adaptive subunits. By this way of thinking, it is abstract information — the gene or economic idea — that is ultimately what is antifragile.

How should we then understand hormesis on the level of the individual organism or cell? Why does hormesis exist in nature? One can grant that life could have evolved without hormesis. But as it turns out, hormesis is everywhere in nature. Defense processes such as the adaptive immune system, melanin pigmentation, and repair processes such as the remodeling of muscle and bone, wound healing, DNA repair, autophagy, etc. were selected for by evolution because they provided certain advantages. The fact that these processes exist, and are even prominent, indicates that they must have had a selective advantage. Organisms that can repair themselves, or even become more resilient in response to a more stressful environment, can outcompete and displace organisms without these hormetic processes.

Mechanisms of hormesis. Evolutionary explanations like this are intriguing. But they don’t explain the mechanics of hormesis, which to me is the most interesting part. How does the organism detect a “stress” and decide what to do with it? We know that the larger system benefits by weeding out the unfit parts, but how does the individual unit benefit from a low dose of “harm”? How is it that we can respond to such a wide variety of stressors – physical insults to the skin or muscle, antigens hitting the skin or mucosa, ingestion of novel or toxic substances — with just the right adaptive responses?

Taleb offers an interesting anwer to this question. While he wants to play down the significance of hormesis as a full fledged example of antifragility, even here he tries to fit the internal mechanics of hormesis into a selectionist model. In a section entitled “Organisms are Populations and Populations Are Organisms”, he draws from an 2011 article by Antoine Danchin et al. in the journal Genes. In Antifragility and Tinkering in Biology, Danchin argues that an organism is actually a hierarchical system of subsystems with “fractal self-similarity”, each subsystem of which operates by evolutionary processes. As Taleb summarizes:

For instance, if you drink a poisonous substance in small amounts, the mechanism by which your organism gets better is, according to Danchin, evolutionary within your system, with bad (and weak) proteins in the cells replaced by stronger–and younger–ones and the stronger ones being spared (or some similar operation). When you starve yourself of food, it is the bad proteins that are broken down first and recycled by your own body–a process called autophagy. This is a purely evolutionary process, one that selects and kills the weakest for fitness. but one does not need to accept the specific biological theory (like aging proteins and autophagy) to buy the general idea that survival pressure within the organism play a role in its overall improvements under external stress. (Antifragile, p. 70-71)

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This perspective has some validity. The immune system, for example, has been modeled as a selectionist system. Danchin’s view also resembles the Neural Darwinism of Gerald Edelman, in which the brain is held to develop and learn by means of selecting neural circuits.

But, while interesting, does selectionism explain everything about hormesis? This is where I’m not sure I can follow Taleb and Danchin. Do autophagy and other hormetic processes really work by weeding out “weak” proteins and selecting for “stronger” proteins? Do the mechanics of hormesis always reduce to the selection of stronger subcomponents? While autophagy does remove damaged or glycated protein from the cell, the damaged protein molecules are of the same type as the undamaged ones. They are not of a distinct “type” that henceforth are downregulated or genetically repressed in favor of “stronger” proteins. There is no “selective pressure” that replaces one type of protein with another, and there is no “replication” of one type of protein over another going forward.

Selectionism has its place in explaining biology and economics, but I doubt that everything reduces to evolutionary theory. At some point, we want to know how hormesis actually works. How do bones and muscle grow stronger? How does exposure to sunlight activate production of melanin and vitamin D? How does the cell repair its DNA? We want to know the details of these wonderful defense and repair systems, so that we can do what is possible to optimize those systems, or at least avoid impairing them.

In economics, we want to know more than just that free competition can lead to better products and services. Which specific practices make companies more resilient? The most interesting business books are not those that proffer abstract theories of competition, but rather those books like Jim Collins’ Good to Great that try to identify the features of companies that survive for decades, through good times and bad.

We want to know how the details of what makes individual people, restaurants and nations thrive. (That is in fact the central theme of this blog that I write!). It’s not enough to tell us that the successful ones are the survivors. We knew that already.

Overcompensation. In “Hormesis is Redundancy”, an anthologized article apparently written after Antifragile, Taleb presents a more plausible–and positive– view of how hormesis makes us stronger:

Hormesis is when a bit of a harmful substance, or stressor, in the right dose or with the right intensity, stimulates the organism and makes it better, stronger, healthier and prepared for a stronger dose the next exposure. That’s the reason we go to the gym, engage in intermittent fasting or caloric deprivation, or overcompensate for challenges by getting stronger….A system that overcompensates is necessarily in overshooting mode, building extra capacity and strength in anticipation for the possibility of a worse outcome, in response to information about the possibility of a hazard. This is a very sophisticated form of discovering probabilities via stressors. (Taleb, p. 347-348 in Brockman, This Explains Everything, 2013) Here, in recognizing hormesis as “overcompensation”, Taleb comes closer to appreciating the power and value of hormesis as an adaptive process. By his definition of antifragility, Taleb seems here to finally give hormesis its due as a legitimate example of antifragility–a process that builds extra capacity in response to stressors. By overcompensating, and not merely restoring equilibrium, the hormesis response in effect predicts or anticipates the future. This is an interesting observation. Still, Taleb doesn’t seem all that interested in probing the details of how hormesis accomplishes this overcompensation. It just does.

Strategies for antifragility. Taleb is not interested in the mechanistic or theoretical details about biology or economics. He is adamantly anti-theortical, and prefers to operate at the level of descriptive phenomenology, of that which can be directly seen or heard with the eyes and ears. He uses a number of metaphorical phrases of his own invention to describe what he considers theoretical excess, including “lecturing birds how to fly” or the “green lumber fallacy”. This latter expression derives from an anecdote about a commodity trader whose success in trading green lumber was based on ignoring any specialized knowledge or “stories” about lumber or what made it green. Instead, the trader focused exclusively on trading patterns or appearances. (I think this is what you call a “technician” as opposed to a “fundamentalist” in the world of investment analysis). The green lumber fallacy, for Taleb, is trying to understand or explain underlying causes or mechanisms, rather than sticking with what is immediately evident.

Taleb brings his skepticism of theory to the practice of hormesis. For example, he embraces practices like intermittent fasting or lifting heavy weights, but resists connecting these to any mechanistic explanations, such as insulin-lowering or micro-trauma to muscles.

I am writing about health, but I do not want to rely on biology beyond the minimum required…I just want to understand as little as possible to be able to look at regularities of experience. (Antifragile, p. 351)

I disagree with Taleb on this point. I think that a deeper, mechanistic understanding of hormesis is worthwhile and productive, because mechanistic hypotheses can tested and point us to new applications. Equally, disproving flawed hypotheses can save us from useless or harmful practices. Nonetheless, Taleb’s phenomenological approach still provides us with some practical strategies for discovering new possible ways to become stronger and more resilient — in health, in wealth, and in outlook.

I’ll try to distill here three of the strategies I found most interesting. Taleb has used his own, idiosyncratic, nomenclature to brand these strategies:

The Barbell Strategy. One of the hallmarks of fragility is that the downside is much worse than the upside. Taleb realized this as an options trader and developed a bimodal investment strategy, using the image of a barbell as a metaphor for pursuing the extremes instead of the average. Rather than “diversify” into areas of average risk, he advises putting the majority of assets into ultra-safe investments like cash, and a small amount–say 10%–into some investments that are riskier but have a disproportionately huge upside. This is an “asymmetric” or lopsided strategy which protects on the downside and has the possibility of great gain on the upside. The barbell strategy is not limited to investment, but can apply to psychology and health.Seneca, the Roman Stoic, realized that wealth can be transient–fragile. To an affluent person, further gains have slight marginal utility, while the risk of losing everything can be devastating. As with other Stoics, Seneca regularly practiced negative visualization (imagining the worst outcome) and voluntary simplicity – traveling lightly and sleeping on the ground — to reduce his fear of the downside and build his appreciation for the upside. Another way that Taleb suggests to apply this strategy is to choose a “safe “career, and supplement this with a wild, creative or fun avocation like writing, skydiving or playing in a rock band.

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How does the barbell strategy apply to health? A great example is combining occasional, high intensity weight lifting or interval training, alternating with long stretches of rest, recovery and “doing nothing”. The intermittent stress of lifting an extreme weight pushes the body to overcompensate and prepare for an even greater future challenge, but the interlude of rest and recovery is restorative and avoids the downside of chronic overuse. We can extend this idea of a bimodal “barbell” strategy to practices such as intermittent fasting or cold showers. The barbell strategy is the exact opposite of the conventional wisdom to engage in moderate aerobic exercise on the treadmill every day, or to eat regular small meals throughout the day. Periodic intense stressors build antifragile resilience — but chronic stress without rest and recovery only wears us down. By alternating between “extremes” of intensity and rest, feast and fast, luxury and poverty — we become more resilient because we increase our range of responsiveness to environmental variability.In my 2011 post on Stress Oscillation

. Asymmetric Optionality. Accepting the idea that we should use the majority of our assets to protect solidly against the downside, how do we decide to invest our money, time, or energies to maximize the upside? Taleb’s answer is to create asymmetric options. An option is not just any “investment” — it is something you can chose to act on, but have no obligation to act upon. Taleb’s idea is to seek out or create options that have a strong upside, but very low cost or downside. He cites the example of the Greek philosopher Thales, who bought the rights to use idle olive oil presses for a very low fee. When an unusually good olive harvest came, he reaped a fortune by renting out the oil presses to growers who had to come to him. Look for asymmetric options in areas besides just investing. For example, if you can secure a rent-controlled apartment, you are protected against rent increases, but if rental rates go down elsewhere, you are free to move. In your contracts, insist on the option to cancel at will without cost. (Don’t sign up for long term phone contracts!).

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So how do we apply asymmetric optionality to improving our health and fitness? The answer lies in my favorite of all Taleb’s strategies for getting stronger…

. Via Negativa. Modern medicine seems overly focused on interventions that provide immediate symptomatic relief. In this, there is a bias to producing immediate and visible short term benefits. This myopia blinds us to longer term or second order effects. Taleb wants to counter this interventional bias — what he calls “iatrogenics” with a corrective:

The first principle of iatrogenics is as follows: we do not need evidence of harm to claim that a drug or an unnatural via positive procedure is dangerous….[I]atrogenics, being a cost-benefit situation, usually results from the treacherous condition in which the benefits are small, and visible–and the costs very large, delayed, and hidden. And of course, the potential cost are much worse than the cumulative gains. (p. 338) Precisely. We are overly impressed with relatively short term studies that show some immediately visible benefit, and we are willing to gamble on this small upside for unknown longer term effects. The downside of the novel intervention may not be known for years. Thalidomide and diethylstilbestrol were drugs developed to provide modest benefits to pregnant mothers, but these were dwarfed by the horrible birth defects that eventually surfaced. More recently, we’ve learned that trans fats and high fructose corn syrup — originally thought to be harmless “innovations” to reduce spoilage or save money — contribute to obesity and metabolic syndrome. But it took decades for this to become clear. A great contemporary example of iatrogenics is the drive to prescribe cholesterol-lowering statins to ever-broader patient groups. Here, Taleb is brilliant in his analysis, including the obsession with “metrics” and the role played by medical liability law: Statins fail in their application the first principle of iatrogenics (unseen harm); further they certainly do lower cholesterol, but as a human your objective function is not to lower a certain metric to get a grade to pass a school-like test, but get in better health. Further, it is not certain whether these indicators people try to lower are causes or manifestations that correlate to a condition–just as muzzling a baby would certainly prevent him from crying but would not remove the cause of his emotions. Metric-lowering drugs are particularly vicious because of a legal complexity. The doctor has incentive to prescribe it because should the patient have a heart attack, he would be sued for negligence; but the error in the opposite direction is not penalized at all, as side effects do not appear at all as being caused by the medicine. (Antifragile, p. 348) Does that mean we should eschew all medical or dietary interventions? Of course not — but we need to be clear about the asymmetric of costs and benefits: Second principle of iatrogenics: it is not linear. We should not take risks with near-healthy people; but we should take a lot, a lot more risks with those deemed in danger. (Antifragile, p. 340)

This leads to Taleb’s prescription for dealing with health issues: Via negativa — “the subtractive way”. Our first instinct should be to subtract “novel” agents from our environment, not add them. Why? Because the downside risks from subtracting (compared with adding) — while real — are typically minimal and easily reversible, while the upside potential can be significant. Our forebears did fine without them, so the potential for harm is minimized. This may sound strange, but we are familiar with elimination diets, where we try to identify possible allergens or food sensitivities by eliminating one food at a time to see if the condition resolves. Many have found that cutting wheat, dairy or other specific foods bring great relief. Taleb goes a step further and advocates eliminating most processed and modern “foods” from the diet. In this regard, he follows a largely Paleo approach. One of the best examples of via negativa is fasting. Taleb seems to be particularly in favor of “randomness in food delivery and composition”, inspired by the fractal approach to eating that Arthur DeVany advocates, for example, in The New Evolution Diet. Interestingly, he also follows the Greek Orthodox custom of fasting during Lent.

Going beyond eating an ancestral diet–or at least pre-modern one–here is an illustrative list of modern innovations that Taleb believe weaken or “fragilize” us, and which we should do without–except in case of severe necessity:

antibiotics

hormone replacement therapy

anti-inflammatory medication

cortisone shots

lobotomies (doesn’t seem so controversial today!)

iron supplementation

sunscreen

disinfectants and excessive hygiene

toothpaste

soy milk

cow’s milk — for people of Mediterranean or Asian descent

fruits — except for “ancient” fruits that are typically more bitter or sour than their modern versions

any drink other than water, wine or coffee (I’m not sure why he excludes herbal teas)

antidepressants

child psychiatry

air conditioning

I must say that I agree with Taleb on many or most of these — with the caveat that occasional or emergency use is acceptable. I would add a few more of my own examples of things we are generally better off doing without — each of which I’ve written about on my blog:

The new insight that Taleb provides is to go beyond mechanistic explanations (e.g. regarding the specifics of adaptation and biological plasticity) to consider the structure of the tradeoff made in considering any intervention. We should replace our current bias for short term interventions with the longer term perspective of “asymmetric optionality” in thinking about risks and benefits in health.

Upcoming presentations at Ancestral Health Society 2013 Conference. Those of you who like this topic will be interested to learn that Nassim Taleb and I have something in common besides an abiding practical interest in hormesis and a skepticism about medical and dietary interventions. We will be both be giving talks at this year’s AHS 2013 Conference in Atlanta in August.

Taleb’s keynote talk is scheduled for Thursday, August 15 at 10:25 a.m., entitled “Antifragile: The Importance of Second Order Effects”

My talk will be Saturday, August 17 at 9:45 a.m, entitled, “The Case Against Nutritional Supplements”

If you peruse the program, you’ll notice themes of evolutionary health and hormesis throughout the conference. The list of presenters and the detailed schedule can be found here at this link:

Ancestral Health Society – Detailed Program

I hope to see some of you there!

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