The argument here is based on the structure of conditional survival probabilities, similar to the one that we used to prove that harm needs to be nonlinear for porcelain cups. Consider that Mother Nature had to have tinkered through selection in inverse proportion to the rarity of the condition. Of the hundred and twenty thousand drugs available today, I can hardly find a via positiva one that makes a healthy person unconditionally “better” (and if someone shows me one, I will be skeptical of yet-unseen side effects). Once in a while we come up with drugs that enhance performance, such as, say, steroids, only to discover what people in finance have known for a while: in a “mature” market there is no free lunch anymore, and what appears as a free lunch has a hidden risk. When you think you have found a free lunch, say, steroids or trans fat, something that helps the healthy without visible downside, it is most likely that there is a concealed trap somewhere. Actually, my days in trading, it was called a “sucker’s trade.”
And there is a simple statistical reason that explains why we have not been able to find drugs that make us feel unconditionally better when we are well (or unconditionally stronger, etc.): nature would have been likely to find this magic pill by itself. But consider that illness is rare, and the more ill the person the less likely nature would have found the solution by itself, in an accelerating way. A condition that is, say, three units of deviation away from the norm is more than three hundred times rarer than normal; an illness that is five units of deviation from the norm is more than a million times rarer!
The medical community has not modeled such nonlinearity of benefits to iatrogenics, and if they do so in words, I have not seen it in formalized in papers, hence into a decision-making methodology that takes probability into account (as we will see in the next section, there is little explicit use of convexity biases). Even risks seem to be linearly extrapolated, causing both underestimation and overestimation, most certainly miscalculation of degrees of harm—for instance, a paper on the effect of radiation states the following: “The standard model currently in use applies a linear scale, extrapolating cancer risk from high doses to low doses of ionizing radiation.” Further, pharmaceutical companies are under financial pressures to find diseases and satisfy the security analysts. They have been scraping the bottom of the barrel, looking for disease among healthier and healthier people, lobbying for reclassifications of conditions, and fine-tuning sales tricks to get doctors to overprescribe. Now, if your blood pressure is in the upper part of the range that used to be called “normal,” you are no longer “normotensive” but “pre-hypertensive,” even if there are no symptoms in view. There is nothing wrong with the classification if it leads to healthier lifestyle and robust via negativa measures—but what is behind such classification, often, is a drive for more medication.
I am not against the function and mission of pharma, rather, its business practice: they should focus for their own benefit on extreme diseases, not on reclassifications or pressuring doctors to prescribe medicines. Indeed, pharma plays on the interventionism of doctors.
Another way to view it: the iatrogenics is in the patient, not in the treatment. If the patient is close to death, all speculative treatments should be encouraged—no holds barred. Conversely, if the patient is near healthy, then Mother Nature should be the doctor.
Jensen’s Inequality in Medicine
The philosopher’s stone explained that the volatility of an exposure can matter more than its average—the difference is the “convexity bias.” If you are antifragile (i.e., convex) to a given substance, then you are better off having it randomly distributed, rather than provided steadily.
I’ve found very few medical papers making use of nonlinearity by applying convexity effects to medical problems, in spite of the ubiquity of nonlinear responses in biology. (I am being generous; I actually found only one explicit use of Jensen’s inequality in one single application—thanks to my friend Eric Briys—and only one that used it properly, so the response “we know that” by medical researchers when the consequence nonlinearity is explained to them is rather lame.)
Remarkably, convexity effects work in an identical way with options, innovations, anything convex. Now let us apply it … to lungs.
The next paragraph is a bit technical and can be skipped.
People with a variety of lung diseases, including acute respiratory distress syndrome, used to be put on mechanical ventilators. The belief was that constant pressure and volume were desirable—steadiness seemed a good idea. But the reaction of the patient is nonlinear to the pressure (convex over an initial range, then concave above it), and he suffers from such regularity. Further, people with very sick lungs cannot take high pressure for a long time—while they need a lot of volume. J. F. Brewster and his associates figured out that dispensing higher pressure on occasion, and low pressure at other times, allowed them to provide a lot more volume to the lungs for a given mean pressure and thus decrease patient mortality. An additional benefit is that an occasional spike in pressure helps to open up collapsed alveoli. Actually, that’s how our lungs function when healthy: with variations and “noise” rather than steady airflow. Humans are antifragile to lung pressure. And this arises directly from the nonlinearity of the response since as we saw everything convex is antifragile, up to a certain dosage. Brewster’s paper went through empirical validation, but this is not even necessary: you don’t need empirical data to prove that one plus one equals two, or that probabilities need to add up to 100 percent.2
It does not look as though people who deal with nutrition have examined the difference between random calories and steady nutrition, something to which we will return in the next chapter.
Not using models of nonlinear effects such as convexity biases while “doing empirical work” is like having to catalog every apple falling from a tree and call the operation “empiricism” instead of just using Newton’s equation.
BURYING THE EVIDENCE
Now some historical background. What made medicine mislead people for so long is that its successes were prominently displayed, and its mistakes literally buried—just like so many other interesting stories in the cemetery of history.
I cannot resist the following illustration of intervention bias (with negative convexity effects). In the 1940s and 1950s many children and teenagers received radiation for acne, thymus gland enlargement, tonsillitis, to remove birthmarks and treat ringworm of the scalp. In addition to the goiters and other late complications, approximately 7 percent of patients who received this radiation developed thyroid cancer two to four decades later. But let’s not write off radiation, when it comes from Mother Nature. We are necessarily antifragile to some dose of radiation—at naturally found levels. It may be that small doses prevent injuries and cancers coming from larger ones, as the body develops some kind of immunity. And, talking about radiation, few wonder why, after hundreds of million of years of having our skins exposed to sun rays, we suddenly need so much protection from them—is it that our exposure is more harmful than before because of changes in the atmosphere, or populations living in an environment mismatching the pigmentation of their skin—or rather, that makers of sun protection products need to make some profits?
The Never-ending History of Turkey Situations
The list of such attempts to outsmart nature driven by naive rationalism is long—always meant to “improve” things—with continuous first-order learning, that is, banning the offending drug or medical procedure but not figuring out that we could be making the mistake again, elsewhere.
Statins. Statin drugs are meant to lower cholesterol in your blood. But there is an asymmetry, and a severe one. One needs to treat fifty high risk persons for five years to avoid a single cardiovascular event. Statins can potentially harm people who are not very sick, for whom the benefits are either minimal or totally nonexistent. We will not be able to get an evidence-based picture of the hidden harm in the short term (we need years for that—remember smoking) and, further, the arguments cu
rrently made in favor of the routine administration of these drugs often lie in a few statistical illusions or even manipulation (the experiments used by drug companies seem to play on nonlinearities and bundle the very ill and the less ill, in addition to assuming that the metric “cholesterol” equates 100 percent with health). 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 the 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.
The same problem of naive interpretation mixed with intervention bias applies to cancer detection: there is a marked bias in favor of treatment, even when it brings more harm, because the legal system favors intervention.
Surgery. Historians show that surgery had, for a long time, a much better track record than medicine; it was checked by the necessary rigor of visible results. Consider that, when operating on victims of very severe trauma, say, to extract a bullet or to push bowels back in their place, the iatrogenics is reduced; the downside of the operation is small compared to the benefits—hence positive convexity effects. Unlike with the usual pharmaceutical interventions, it is hard to say that Mother Nature would have done a better job. The surgeons used to be blue-collar workers, or closer to artisans than high science, so they did not feel too obligated to theorize.
The two professions of medical doctor and surgeon were kept professionally and socially separate, one was an ars, the other scientia, hence one was a craft built around experience-driven heuristics and the other reposed on theories, nay, a general theory of humans. Surgeons were there for emergencies. In England, France, and some Italian cities, surgeons’ guilds were merged with those of barbers. So the Soviet-Harvardification of surgery was for a long time constrained by the visibility of the results—you can’t fool the eye. Given that for a long time people operated without anesthetics, one did not have to overly justify doing nothing and waiting for Nature to play her role.
But today’s surgery, thanks to anesthesia, is done with a much smaller hurdle—and surgeons now need to attend medical school, albeit a less theoretical one than the Sorbonne or Bologna of the Middle Ages. By contrast, in the past, letting blood (phlebotomy) was one of the few operations performed by surgeons without any disincentive. For instance, back surgery done in modern times to correct sciatica is often useless, minus the possible harm from the operation. Evidence shows that six years later, such an operation is, on average, equivalent to doing nothing, so we have a certain potential deficit from the back operation as every operation brings risks such as brain damage from anesthesia, medical error (the doctor harming the spinal cord), or exposure to hospital germs. Yet spinal cord surgery such as lumbar disc fusion is still practiced liberally, particularly as it is very lucrative for the doctor.3
Antibiotics. Every time you take an antibiotic, you help, to some degree, the mutation of germs into antibiotic-resistant strains. Add to that the toying with your immune system. You transfer the antifragility from your body to the germ. The solution, of course, is to do it only when the benefits are large. Hygiene, or excessive hygiene, has the same effect, particularly when people clean their hands with chemicals after every social exposure.
Here are some verified and potential examples of iatrogenics (in terms of larger downside outside of very ill patients, whether such downside has been verified or not)4: Vioxx, the anti-inflammatory medicine with delayed heart problems as side effects. Antidepressants (used beyond the necessary cases). Bariatric surgery (in place of starvation of overweight diabetic patients). Cortisone. Disinfectants, cleaning products potentially giving rise to autoimmune diseases. Hormone replacement therapy. Hysterectomies. Cesarean births beyond the strictly necessary. Ear tubes in babies as an immediate response to ear infection. Lobotomies. Iron supplementation. Whitening of rice and wheat—it was considered progress. The sunscreen creams suspected to cause harm. Hygiene (beyond a certain point, hygiene may make you fragile by denying hormesis—our own antifragility). We ingest probiotics because we don’t eat enough “dirt” anymore. Lysol and other disinfectants killing so many “germs” that kids’ developing immune systems are robbed of necessary workout (or robbed of the “good” friendly germs and parasites). Dental hygiene: I wonder if brushing our teeth with toothpaste full of chemical substances is not mostly to generate profits for the toothpaste industry—the brush is natural, the toothpaste might just be to counter the abnormal products we consume, such as starches, sugars and high fructose corn syrup. Speaking of which, high fructose corn syrup was the result of neomania, financed by a Nixon administration in love with technology and victim of some urge to subsidize corn farmers. Insulin injections for Type II diabetics, based on the assumption that the harm from diabetes comes from blood sugar, not insulin resistance (or something else associated with it). Soy milk. Cow milk for people of Mediterranean and Asian descent. Heroin, the most dangerously addictive substance one can imagine, was developed as a morphine substitute for cough suppressants that did not have morphine’s addictive side effects. Psychiatry, particularly child psychiatry—but I guess I don’t need to convince anyone about its dangers. I stop here.
Again, my statements here are risk-management-based: if the person is very ill, there are no iatrogenics to worry about. So it is the marginal case that brings dangers.
The cases I have been discussing so far are easy to understand, but some applications are far more subtle. For instance, counter to “what makes sense” at a primitive level, there is no clear evidence that sugar-free sweetened drinks make you lose weight in accordance with the calories saved. But it took thirty years of confusing the biology of millions of people for us to start asking such questions. Somehow those recommending these drinks are under the impression, driven by the laws of physics (naive translation from thermodynamics), that the concept that we gain weight from calories is sufficient for further analysis. This would be certainly true in thermodynamics, as in a simple machine responding to energy without feedback, say, a car that burns fuel. But the reasoning does not hold in an informational dimension in which food is not just a source of energy; it conveys information about the environment (like stressors). The ingestion of food combined with one’s activity brings about hormonal cascades (or something similar that conveys information), causing cravings (hence consumption of other foods) or changes in the way your body burns the energy, whether it needs to conserve fat and burn muscle, or vice versa. Complex systems have feedback loops, so what you “burn” depends on what you consume, and how you consume it.
NATURE’S OPAQUE LOGIC
At the time of this writing, the biologist Craig Venter is engaging in the creation of artificial life. He conducted experiments and stated them in a famous paper titled “Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome.” I have an immense respect for Craig Venter, whom I consider one of the smartest men who ever breathed, and a “doer” in the full sense of the word, but giving fallible humans such powers is similar to giving a small child a bunch of explosives.
If I understand this well, to the creationists, this should be an insult to God; but, further, to the evolutionist, this is certainly an insult to evolution. And to the probabilist, like myself and my peers, this is an insult to human prudence, the beginning of the mother of all exposures to Black Swans.
Let me repeat the argument here in one block to make it clearer. Evolution proceeds by undirected, convex
bricolage or tinkering, inherently robust, i.e., with the achievement of potential stochastic gains thanks to continuous, repetitive, small, localized mistakes. What men have done with top-down, command-and-control science has been exactly the reverse: interventions with negative convexity effects, i.e., the achievement of small certain gains through exposure to massive potential mistakes. Our record of understanding risks in complex systems (biology, economics, climate) has been pitiful, marred with retrospective distortions (we only understand the risks after the damage takes place, yet we keep making the mistake), and there is nothing to convince me that we have gotten better at risk management. In this particular case, because of the scalability of the errors, you are exposed to the wildest possible form of randomness.
Simply, humans should not be given explosive toys (like atomic bombs, financial derivatives, or tools to create life).
Guilty or Innocent
Antifragile: Things That Gain from Disorder Page 40
