Friday, February 22, 2013

How To Practice Medicine in a World We Can Never Truly Understand


Central to the problem of how best to live in a world that we cannot understand is how to regard:

“The Extended Disorder Family (or Cluster): (i) uncertainty, (ii) variability, (iii) imperfect, incomplete knowledge, (iv) chance, (v) chaos, (vi) volatility, (vii) disorder, (viii) entropy, (ix) time, (x) the unknown, (xi) randomness, (xii) turmoil, (xiii) stressor, (xiv) error, (xv) dispersion of outcomes, (xvi) unknowledge.  (Nassim Nicholas Taleb, Antifragile, London: Allen Lane, 2012)
To this impressive list, I would add seventeenth and eighteenth items:  failure and death.  All of these characteristics scare and frighten most of us, and so we do our best to avoid them.

Despite the popularity of self-help books emphasizing the pursuit of happiness, a vocal minority has advocated embracing all of the above negative items in order to live fully and successfully.

Eric G. Wilson perhaps provides the best overview of this minority report when he observes that

“To desire only happiness in a world undoubtedly tragic is to become inauthentic, to settle for unrealistic abstractions that ignore concrete situations.”
And
“Our passion for felicity hints at an ominous hatred for all that grows and thrives and then dies.” (Eric G. Wilson, Against Happiness, New York:  Sarah Crichton Books, 2008)

To be alive and to realize that you are going to die means being insecure and vulnerable.  According to Martha Nussbaum one should embrace this uncertainty.

“To be a good human is to have a kind of openness to the world, an ability to trust uncertain things beyond your own control, that can lead you to be shattered in very extreme circumstances for which you were not to blame. That says something very important about the ethical life:  that it is based on a trust in the uncertainty, and on a willingness to be exposed.  It’s based on being more like a plant than a jewel: something rather fragile, but whose very particular beauty is inseparable from that fragility.” (Oliver Burkeman, The Antidote, New York:  Faber and Faber, Inc., 2012).

The Stoics may have been the first to realize that embracing the negative can be a useful tool for human beings attempting to lead a meaningful life.  William Irving in A Guide to the Good Life:  The Ancient Art of Stoic Joy describes their negative visualization as imagining that the worst possible outcome may occur.  And if bad things do happen that is the way it is supposed to be.  Marcus Aurelius advised us to “constantly regard the universe as one living being, having one substance and one soul. (http://classiclit.about.com/od/aureliusmarcus/a/aa_maurelius.htm)  Whatever happens at all happens as it should; you will find this true, if you watch narrowly.” (http://en.wikiquote.org/wiki/Marcus_Aurelius)

By concentrating on this glass half full philosophy, the Stoics solved two of the more vexing problems that humans encounter when they pursue happiness.  The hedonic treadmill effect where sources of pleasure last only a short period of time is minimized when one meditates on the likely negative outcome of everything in life.  Negative visualization also decreases the anxiety associated with the irrational fears that our minds come up with when worrying about the unknown future. 

Oliver Burkeman in The Antidote describes how Albert Ellis, the second most influential psychotherapist of the twentieth century, advocated a similar negative approach to life.  He differentiated become a terrible outcome and a merely undesirable outcome, and he argued that it could always be worse.  In advising an anxious and ambivalent woman trying to decide if she should move to be with her boyfriend, Ellis shouted:

“So maybe he turns out to be a jerk, and you get divorced! That would be highly disagreeable! You might feel sad! But it doesn’t have to be awful.  It doesn’t have to be completely terrible.”

One of the things that troubles me most about the current American fascination with happiness is how self-absorbed and superficial the entire enterprise can become.  Those that are most concerned with happiness often appear to be ignoring much of reality.  Taleb in Antifragile defines via negativa as focusing on what something is not and he recommends using it as recipe for what to avoid, what not to do.  He also observes that we know what is wrong with more certainty than we know what is right.  Applying these concepts to happiness, he believes the subject is best dealt with as a negative concept:

“Instead, they should be lecturing us about unhappiness (I speculate that just as those who lecture on happiness look unhappy, those who lecture on unhappiness would look happy).”

Which brings us to Alan Watts who in The Wisdom of Insecurity makes two very important points.  The first is that

“There is a contradiction in wanting to be perfectly secure in a universe whose very nature is momentariness and fluidity.”
His second key observation in this important book about our inability to control events in a world that we truly do not understand is his fascination with the law of reversed effort.

“When you try to stay on the surface of the water, you sink; but when you try to sink, you float…Insecurity is the result of trying to be secure…contrariwise, salvation and sanity consist in the most radical recognition that we have no way of saving ourselves.”

This realization that the world we live in is essentially insecure and that denying this reality makes us unhappy is the message of Pema Chodron.  She writes, “Things are not permanent, they don’t last, there is no final security.” 

What does the realization that we will never truly understand the world we live in mean for those of us who are physicians?  Should the discussion above change the way we view medicine?  David Agus in the End of Illness and Taleb in Antifragile provide us with guidance about medicine in a complex emergent system world.

Having graduated from Case Western Reserve School of Medicine in 1980 and having trained at UCSF as an academic anatomic pathologist, I am steeped in the traditional approach to health care where we assume we can understand the world of medicine.  The biomedical model reduces every illness to a biological mechanism of cause and effect, and physicians diagnose diseases and then treat them.  Health is defined as absence of disease.  The patient story and experience is subjective and untrustworthy in comparison to the test results emanating from my pathology laboratory, which are objective and true.  Generalists are replaced by specialists who regard cure as the only important goal.  And pathologists are the most important of the specialists because treatment selection and administration has to await the diagnosis rendered in the pathology laboratory. 

Agus labels the traditional approach “the germ theory of disease, which dominated, and in many ways defined, medicine in the twentieth century.”  “The treatment only cared about the invading organism…it didn’t care to define or understand the host (the human being).”

Agus, an academic oncologist and founder of both a proteomics and a genomics biotech start up company, replaces the medical status quo with a system biology approach. “It is important to approach your health in general from a lack of understanding.  Honor the body and its relationship to disease as a complex emergent system that you many never fully comprehend.”  His conclusion that one does not need to understand cancer to treat it is controversial. 

Taleb’s Antifragile provides an approach to living in a world we do not understand by applying his study of the statistics of random events and his experience as an options trader.  Taleb compares and contrasts a fragile and antifragile approach to everything from science, business, errors, systems, and Greek mythology.  In science for example, the fragilista who thinks he understands everything causes fragility by depriving variability loving systems of variability and error loving systems of errors; he favors directed research and grand theories.  The opposite scientist is a practitioner who tries to understand how things react to volatility and errors, and he favors stochastic tinkering or bricolage to grand overarching theories. 

The French biologist Francois Jacob used the term bricolage to describe the trial and error way that nature exploits optionality.  Jacob gives the example of how half of all embryos undergo spontaneous abortion in the uterus, which is easier than designing the perfect baby by blueprint.  Another example of bricolage would be the way that genes that work in simple animals are retained and utilized for similar functions in higher animals.  This concept of “trying to make do with what you’ve got by recycling pieces that would be otherwise wasted” illustrates how nature substitutes optionality for intelligence. 

Saras Sarasvathy’s study of 45 successful entrepreneurs shows how the bricolage approach can be applied to start-up companies.  In Sarasvathy’s effectuation system causally minded people (fragilistas in Taleb’s book) favor a directed plan to achieve their goal.  Effectually minded people, on the other hand, take a trial and error approach to see what they can make out of the means and materials that are on hand.  Applying the bird in the hand principle and the principle of affordable loss, effectually minded people forge ahead to see what happens.  Sarasvathy found that most successful entrepreneurs were effectually minded. (www.effectuation.org)   A conclusion that would please Taleb.

When Taleb focuses on medicine, he concentrates on the problems of iatrogenics and the agency problem.  Iatrogenics literally means caused by the healer as iatros means healer in Greek. 

“Every time you visit a doctor and get a treatment, you incur risks of such medical harm, which should be analyzed the way we analyze other trade-offs:  probabilistic benefits minus probabilistic costs.”

The agency problem is when the agent has personal interests that are different from those of the principal who uses the agent’s services

“An agency problem, for instance, is present with the stockbroker and the medical doctor, whose ultimate interest is their own checking account, not your financial and medical health, respectively, and who give you advice that is geared to benefit themselves.”

Taleb notes that Montaigne recognized the agency problem when he wrote, “No doctor derives pleasure from the health of his friends, wrote the Greek satirist, no soldier from the peace of his city.”

Taleb develops simple decision rules for dealing with health and wellness.  Using his concept of via negativa that we encountered above when we discussed happiness, his first rule is “only resort to medical techniques when the health payoff is very large (say, saving a life) and visibly exceeds its potential harm, such as incontrovertibly needed surgery or lifesaving medicine (penicillin). 

Taleb believes “we do not need evidence of harm to claim that a drug or an unnatural via positiva procedure is dangerous.”  To emphasize that harm can be difficult to appreciate, he notes that harm often occurs in the future and that the past does not tell one much about rare random events.  The Turkey Problem makes this point.

“The turkey is fed by the butcher for a thousand days, and every day the turkey pronounces with increased statistical confidence that the butcher ‘will never hurt it’ – until Thanksgiving, which brings a Black Swan revision of belief for the turkey.”

Following Taleb’s advice would have avoided the harm caused by Thalidomide (birth defects) and Diethylstilbestrol (delayed cancer in daughters).

“Iatrogenics, being a cost-benefit situation, usually results from the treacherous conditions in which the benefits are small, and visible – and the costs very large, delayed, and hidden.  And of course, the potential costs are much worse than the cumulative gains.”

Another Taleb rule is “we should not take risks with near-healthy people; but we should take a lot, a lot more risks with those deemed in danger” because iatrogenics has a nonlinearity response. 

“This means that we need to focus on high-symptom conditions and ignore, I mean really ignore, other situations in which the patient is not very ill.”

Taleb also recognizes that the paucity of medical articles reporting negative results has contributed to the problem of overtreatment with sometimes disastrous results.

“What made medicine mislead people for so long is that is successes were prominently displayed, and its mistakes literally buried  -- just like so many other interesting stories in the cemetery of history.”

Ben Goldacre in the New York Times recently discussed this point when he wrote about the recall of a Johnson and Johnson artificial hip that experienced a 40% failure rate:

The best evidence shows that half of all the clinical trials ever conducted and completed on the treatments in use today have never been published in academic journals. Trials with positive or flattering results, unsurprisingly, are about twice as likely to be published — and this is true for both academic research and industry studies.” (http://www.nytimes.com/2013/02/02/opinion/health-cares-trick-coin.html)

Perhaps the best way to end this discussion of how to live wisely in a world that we can never truly understand is to give Taleb the final word:

“If there is something in nature you don’t understand, odds are it makes sense in a deeper way that is beyond your understanding.  So there is a logic to natural things that is much superior to our own.  Just as there is a dichotomy in law:  innocent until proven guilty as opposed to guilty until proven innocent, let me express my rule as follows; what Mother Nature does is rigorous until proven otherwise; what humans and science do is flawed until proven otherwise.”



















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