Nothing here since January, 2009! Why? I’m reminded of the parents who had a child who never spoke. They took him to pediatricians, speech therapists, witch doctors: everyone they thought could help. Not a syllable came forth. They accepted that he was mute, and got on with it. One day at breakfast, when the child was six years old, he said, “This toast is burnt.” The parents almost collapsed, and with tears in her eyes, the mom said, “Johnny, you can talk!” The child responded, “Of course I can talk; I’m six years old.” Bewildered, his mom asked, “So, why haven’t you ever said anything before?” Without hesitation, the boy replied, “Up ’til now, everything’s been OK.”
So, here’s the deal. I wrote a number of posts in 2008 and 2009 about the medical profession and medical marketing.The blog generated about 10,000 hits, but not much discussion. At the time, I didn’t have anything else to say that I felt was important or revelatory. Now I do. If you have ever read my posts, you know that I am searching, and that I am a student of bias. I rejoice in learning how things work: not how they seem to work, nor how we would like for them to work, nor what the majority thinks about how things work, but how the evidence describes how things work.
Enter Nrf2. Nrf2 is an abbreviation for Nuclear factor (erythroid-derived 2)-like 2, also known as NFE2L2. Your doctor knows this, right? Wrong! When we matriculate into medical school, our teachers typically are not medical doctors, but PhD’s, who have extensive, up-to-the-minute knowledge of their niche. Among the first things they teach us are these two:
- a vocabulary that is the equivalent of a foreign language, and like any foreign language, it is mastered when the words themselves cause concepts to appear in the brain without translation.
- basic medical sciences.
Your doctor (and I) have mastered the vocablulary.We can read the peer-reviewed articles, and we have at least the potential to understand what they say. But the basic sciences? There are few practicing physicians who could pass a current freshman medical school test on any of the basic sciences, and the information is changing at an almost exponential rate. Nrf2 is one of those things that basic scientists, in this case, biochemists, know about that your doctor does not.
Here’s the story. Did you know that oxygen is the source of our ultimate demise? We have to have it to survive, and to create the energy we use daily. But, in producing that energy, one of the products is a nefarious substance called “reactive oxygen species” (ROS). ROS will kill any oxygen-dependent organism. So, it is not surprising that all aerobes have evolved a method for dealing with these destructive ROS “free radicals”. The 25,000 or so genes in the human genome include 4-6 thousand genes that have evolved specifically to deal with ROS. That’s about a quarter of all the instructions that make us who and what we are. How do they do this? By up-regulation of protective enzymes that neutralize ROS, and by down-regulation of associated inflammatory and fibrotic processes stimulated by ROS. This is important. For me, it is revelatory. For your doctor? Maybe not so much.
It was a biochemist who first discovered the protective enzyme, SOD (superoxide dismutase). His name is Joe McCord. Your doctor has his own Wikipedia page, right? As Dr. McCord puts it, the discovery of SOD was the beginning of the solution, but no one knew the problem it solved. And what is the problem? Aging and degeneration itself! What is aging? Surprisingly, to a biochemist/medical school professor like Joe McCord, aging is defined as a ratio. The numerator is the level of protective antioxidant enzymes one’s genes produce, and the denominator is the amount of oxygen one consumes. Up until about the age of 18 -20 years, that ratio in genetically “normal” folks is such that very little degeneration occurs. You’ll starve if you are a doctor specializing in teen-age heart attacks, strokes, hypertension, osteoarthritis, type 2 diabetes, Alzheimer’s, Parkinson’s Disease, coronary bypasses and stents (continue the list to include almost everything non-infectious that eventually gets us), but you’ll be overworked with the same disorders if your field is geriatrics. Why? The ratio of protective enzymes to destructive ROS declines as we age, and oxygen gradually destroys us all.
What if we could stimulate our genes to rev up the protective enzyme levels to what they were when we were young? It would make front-page headlines! Fox News and PBS would find common ground featuring it! Your doctor would be calling YOU to make sure you were aware of this wellness breakthrough! NOT!!
Nrf2 was described and isolated in 1994. It’s role as the key activator for all the “survival genes” has been known to biochemists for over 10 years. There are 2088 peer-reviewed articles about it (as of today) listed on the National Institutes of Health website, pubmed.gov. Researchers in both independent university roles and as employees of pharmaceutical companies have been frantically searching for methods to activate Nrf2 safely, both to prevent and to treat the ravages of human physical degeneration. It could play a major role in reducing our runaway healthcare costs. EVERYONE’S TALKING ABOUT IT.
Well, maybe not. In fact, among all my physician friends to whom I have mentioned Nrf2, only one has ever heard of it. Furthermore, that one physician is the only one of my doctor friends who seems remotely interested in the concept. What’s going on here?! Artificial-intelligence researcher Eliezer Yudkowsky has observed: You know better than to think that a random doctor will have extraordinary clarity of mind and the power to find truth within confusion. Our medical education system stops teaching science and the scientific method after the early years of medical school; from then on, we learn and memorize prescribed solutions for various problematic scenarios.The system eschews independent thought and investigation. In fact, we are held legally liable for employing methods that deviate from the accepted norms. Those norms come down to practicing physicians through established channels, as I’ve previously mentioned here, here, here, and here. Currently, none of the established channels involves Nrf2 nor its activation, and few doctors make the effort to search for the truth within the confusion.
Enter what I will call a form of “intellectual attribution bias”. According to Michael Shermer in his book, Why People Believe Weird Things, because of this cognitive bias, smart people are about nine times more likely to attribute their own position on a given subject to rational reasons than they are other people’s position, which they will attribute to emotional reasons. Although major pharmaceutical companies are trying to develop synthetic Nrf2 activators as prescription drugs, the only currently available clinically effective Nrf2 activator is a compound of natural phytonutrients called Protandim. It is classified by the FDA not as a drug, but as a dietary supplement, and it is available not by prescription or in pharmacies, but only through network marketing.
In spite of peer-reviewed studies listed on pubmed.gov documenting the compound’s ability to raise Nrf2 activation to unprecedented levels, and subsequently lower oxidative stress to unprecedented levels, practicing physicians are not likely to give it any credence because it doesn’t fit in the mold of their established channels of information. Their position seems to be: “I am an expert, and I haven’t heard of Nrf2 activation. Now you’re telling me that a network marketed supplement could be the most important advancement yet in my own specialty, and I don’t know about it? It’s bulls**t.”
UPDATE: Biogen’s synthetic Nrf2-activator drug Tecfidera was approved in the Spring of 2013 for the treatment of Multiple Sclerosis. Available by prescription only at a cost of about $50,000 annually. Biogen’s research shows that Tecfidera has about 50% of the Nrf2 activation of the natural-ingredient compound, Protandim, which costs $40/month, without Tecfidera’s side-effects.
Here’s an exercise your doctor hasn’t done: go to pubmed.gov, and in the search box enter “Nrf2″ followed by the name of any disorder that interests you, e.g., “Nrf2 diabetes”. As one enters disorder after disorder, and sees the scientifically documented correlation with levels of Nrf2 activity, one comes to realize that we have evolved to deal with oxygen consumption in a healthy way until we reach the years of reproduction, and then our Nrf2 activity drops off and we begin to die. We can begin to control that now by controlling Nrf2 activation. Doctors treat symptoms and the results of disease. Nrf2 activation removes the cause. The solution, or the beginning of it, has come along: Nrf2 activation. Your doctor doesn’t know about it. Tell him/her. He’ll tell you it’s bulls**t.
If you want to know more, click on “contact retired urologist” at the top of the page and send me a message. Or educate yourself at ABCliveit.
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I’m altruistic, which isn’t the same thing as being kindly. I hold doors open for little old ladies. That’s not the same as liking the people I meet. – Eliezer Yudkowsky
You know better than to think that a random doctor will have extraordinary clarity of mind and the power to find truth within confusion. It is not any different in AGI. – Eliezer Yudkowsky
There is a dominant part of me that believes one should never be punished for telling the truth. But that’s not realistic, is it? And so the conflict. Rational thought and behavior trumps etiquette, yet much of life (the way it is actually lived) requires going along to get along.
Suppose a doctor happened to possess a combination of the qualities Yudkowsky describes: an altruist with extraordinary clarity of mind and the power to find truth within confusion. That’s what you’d want in a doctor, right? Apparently not, if public record is of any significance. In fact, I would go so far as to predict that such a doctor would have a miserable litany of malpractice tort actions. Note that I did not say “a miserable record of acts of malpractice.” There is a wide berth between actual malpractice and a tort claim of malpractice.
While it may be quite an unpopular concept, I am persuaded that there exists an independent, sometimes antithetical, relationship between true altruism and kindliness. But try to conduct a medical practice based on true altruism and rational principles: you will be among the leaders in malpractice tort actions. The reason: the altruistic action may not seem like a kind action.
The actual practice of medicine is structured around historical outcomes, either clinically or experimentally. The inescapable problem is that no one knows exactly how humans work. There aren’t any treatments that always work. Consequently, the best-intentioned, most conscientious doctor, the one with extraordinary clarity of mind and the power to find truth within confusion, gets bad results. Since it is not truly science, there is always someone who will say the outcome would have been better if so-and-so. And the tort process begins. Unfortunately, not all doctors are like the one described. They are likely to create even worse outcomes. So, naturally, they will experience even more malpractice claims, right? Not necessarily.
Most instances of actual malpractice do not result in litigation; there are so many available references to this that I am not citing one. What converts a patient into a plaintiff? According to the loss-prevention program of my malpractice insurer, plaintiff polls show that the most important factor is the doctor’s attitude. Kindliness and empathy trump clarity of mind and the power to find truth. My medical generation had no courses in kindliness; in terms of skill and rationality, half of all medical students graduate in the lower half of the class. If kindliness and skill are independent variables, what are the chances that a doctor possesses both? I don’t know; I’m just asking.
Altruistic rationalism is Kind; it is not always kindly. Kill ’em with kindliness.
Addendum after comment: My first father-in-law was a pediatrician. He claimed that most of his patients would recover from their illnesses if he did nothing; a very few would not recover no matter what he did; and in the remainder, he hoped to make a difference in the outcome. In my own practice of penile prosthesis surgery, once the surgical wound was closed, there was essentially nothing I could do to improve the outcome. Because of this, in the early portion of my career, I scheduled my prosthesis patients to return two weeks post-op, the time when I intended to inflate the device to prevent healed wrinkles. During that two-week interval, the patients experienced impressive swelling and discoloration, as they had been advised to expect. My receptionist and my office manager, after a while, suggested that I begin seeing the patients three days post-op, to relieve their anxiety. Their people-skills were far superior to mine, and I followed their advice. Patient satisfaction skyrocketed, although outcomes were unchanged.
To combine these two stories (mine and the pediatrician’s), I firmly believe that people want to be told that everything will be OK. The problem is that some will not be OK, in spite of doing everything “correctly”. Occasionally, as the pediatrician told me, a child with a viral upper respiratory infection will go on to develop viral pneumonia. The parent then wants to know, “Why didn’t you give my child antibiotics?” The doctor knows that not only will antibiotics not help, but also they will actually increase the chance of secondary bacterial infection. After years of dealing with angry parents over unavoidable outcomes, the pediatrician treats the parent, rather than the child; antibiotics are started from the get-go. At this point, one ceases to be a doctor, and enters into the field of public relations.
With prostheses, assuming the surgery was done correctly, the big cause of failure is bacterial infection. Infection occurs at the time of surgery, or perhaps a few hours later, the source almost always being the patient’s own skin or fluids (this has been documented by tracer analyses). In my practice, the rate was just under 1%. Nothing can be done to prevent early signs of infection from progressing to conditions that demand removal of the device. Patients cannot be convinced of this. They intuitively feel that one-chance-in-a-hundred means, “it can’t happen to me.” Consequently, the post-op care in such patients turns to techniques of assuagement and demonstration of concern, which only postpone the ultimate outcome, and actually cause the patient an unnecessarily long convalescence. With the “public relations” approach, the failed patient is unhappy; with straight-forward fact-based actions, he is angry. Angry patients are the first step toward malpractice tort actions. Since we can’t completely eradicate infections, we begin to focus on eradicating lawsuits.
And then we’re not doctors.
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As my medical school years drew to a close, each of us faced the choice of residency that would determine how we spent our professional lives. A close friend and member of AOA, the medical honor society comparable to Phi Beta Kappa or Law Review, declared that he had chosen OB/GYN. He and I had shared what I felt was a miserable experience as “acting interns” on the obstetrics service our senior year, so his choice astounded me.
His answer was seminal: “Have you noticed the size of the textbook?” Indeed, the OB/GYN text was far smaller than that of any other subject we studied. “I think it’s possible to learn everything there is to know about OB/GYN. I can be an expert.” Perhaps he was citing the mental comfort associated with mastery of a skill, and the unlikelihood that he would find himself in a situation beyond his capabilities, akin to a world-class martial arts expert walking alone at night. I suspect the knowledge that one’s work was done as well as could be done would provide substantial comfort, especially if one were well-paid, and the importance of that work were protected and promoted by a guild system. [NOTE: in those days, there was little concept of medical malpractice, a scourge which subsequently would hit the OB/GYN specialty harder than any other.]
Yet, I think his answer (and his career choice) may have been more instinctive, and perhaps outside his conscious awareness: the possibility of being an expert may have been subsumed by the possibility of being recognized as an expert. Dr. Robin Hanson, on the Overcoming Bias blog, initiated a discussion of a similar concept, referring to “expert at” versus “expert on“, in which the former could perform successfully and the latter could talk about it successfully. I’m referring to a third entity: an expert on a topic who also is an expert at that topic. He is an expert by all practical considerations, and he is well-remunerated. Is that enough? Perhaps not.
I have observed a distinct change in attitude when the expert-aspirant is exposed to his peers. In my own field, I wanted to be, planned to be, and worked to be the best in the world. In my own mind, I achieved that (male surgical sexual medicine is a very small pond for any size frog), and I was compensated financially in adequate fashion. I want to be satisfied with the knowledge that my work was of superior technical and ethical quality. But it’s a self-edited summary; often (not always) at the highest levels of anything, self-satisfaction seems overrated, and inadequate. At a conference of IPP (inflatable penile prosthesis) technical experts, early in my career, I was seated at dinner next to a surgeon who was prolific in numbers of successful operations. In fact, studying his methods had caused me to take a number of steps that benefitted both my technical skills and my practice success. Because of his influence, and my subsequent personal experience, he and I both used the same brand of IPP in our patients. Neither of us was in academics, so our “fame” came only from our patients and from the recognition of the manufacturer. He mentioned that he had performed “3- or 4-hundred” procedures that year. Unlike some areas of surgery, the number of IPP surgeons who ever perform more than 100 procedures in a year can be counted on two hands. My pride was piqued, and I replied, “I did 201, and Mr. X (the manufacturer CEO) told me that was tops in the world.” When I was just starting, this same surgeon had asked me to join his practice; after the dinner encounter, he was never friendly to me again. It was vanity versus vanity. Of note, I am very unpopular with the “experts on” in my field, those I call the “thought leaders”, none of whom are “experts at”. It’s the recognition, stupid.
Lest you think that the self-satisfied expert at/expert on doctor is immune to this vanity, give him a chance for recognition. Pharmaceutical and device manufacturers have caught on to this weakness in spades. The opportunity to be the star at doctor-to-peer lectures and presentations has changed the attitude of many a current physician, and strongly influenced his practice habits. Even when one has reached the pinnacle of both actual and recognized expertise, the vanity drive remains strong. Dr. Michael DeBakey gave the AOA visiting professor lecture during my junior year. I don’t remember much of what he said, but one quote has stayed with me: “I could make a career simply correcting the mistakes of other vascular surgeons.” Probably a true statement, especially at the time, but of what value was this knowledge to junior medical students? Could there be any doubt that recognition was the driving force?
Recently on Overcoming Bias, the smartest of the smart have shown not only are they are not immune to the vanity of the experts, they actually are as pedestrian as the rest of us when it comes to this human frailty. In the posts and discussions here, here, and here, it’s all about who is the smartest, who is the best qualified, and who is the leading expert. One would think pride in one’s intelligence is severely misplaced. As one of the main posters, Eliezer Yudkowsky, has said, “We are the cards we are dealt, and intelligence is the unfairest of all those cards.” Yet note the ego-involvement. One would think that accomplishment was a far better source of pride. And if that accomplishment has not yet occurred? Such encounters as this are the result. I choose Mr. Yudknowsky as an example only because he is a dedicated student of the human thought process, and one of two main writers on a blog dedicated to eradicating bias. If it can happen to such as him, perhaps it’s innate.
*Pro tip*:The ultimate goal is not only that I succeed, but also that you fail.
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