Tag Archives: healthcare

Knock Out Mouse Revolution

mighty-mouse-cartoon-clipart-16

Standing in the New Orleans convention center felt a little eerie. The interior was clean and neat. It looked like an airport. Still, I could not help but recall images of Katrina, when the huge edifice had become a beacon of false hope, luring the populace through its doors with the promise of aid, only to leave those who entered trapped like rats.

We had come to a conference to learn about endocrinology, which I had not considered too creepy before. I was wrong.

The proceedings began innocently. Hundreds of physician scientists, and I, filed quietly into a giant auditorium. I want to make clear my lack of qualifications relative to the rest of the group. I am no scientist, and barely a physician. I would much rather read philosophy books and climb around on crumbly sandstone towers than pipette solutions into a gel matrix.

But my job is mostly about helping people protect themselves from diabetes. Plus my wife had a poster to present. So, there I was, attending as an imposter.

The keynote speaker got a prolonged introduction. He deserved it. He was an important person with important research credentials. It was the kind of introduction where a name is never mentioned, for dramatic effect, and because everybody already knows exactly who the subject is. It is a an effective strategy for generating anticipation in the majority who are already quite familiar with the speaker, as well as in those who have never heard of him. It works for everyone, except my wife. She is honest to a fault, and that means that she is a real subject-object-verb kind of person. When presented with a dramatic, obscure speech, her attention lapses. As the speaker walked onstage to the sound of his name, she asked me who this Francis Collins person was.

After a long moment’s reflection, I told her that Francis Collins was a bad philosopher. She seemed to accept my summary, because she promptly settled back in her theater chair to nap through the rest of the lecture. I could not sleep, though I was feeling a little jet lag as well. The lecture was fascinating. Dr. Collins had been right in the middle of genetic research since the beginning of the human genome project, and he took the audience on a trip through the whole endeavor, right up to the current moment: the Big Data revolution.

The Big Data revolution referred to the use of advanced mathematical and computing techniques to sort through scads of data for druggable targets in endocrine diseases. The special techniques had become necessary because the database had exploded. Dr. Collins and his compatriots had deciphered the genomic book of life, but when they sat down to read it, they discovered that they needed a lamp, reading glasses, bookmarks, and indeed, the semantics of the language. The genes turned out to be active in the context of all sorts of transcription factors, promotors, coactivators, corepressors, etc. There was layer upon layer of conditionals which gave meaning to the genetics.

The source of the Big Data revelation was the knockout mouse. The knockout mouse and its cousins, the knockin mouse and the humanized mouse, were what happened when researchers turned to their traditional test subjects with gene manipulation techniques learned in dissecting the genome. By studying mice with selectively induced genetic defects, the researchers had produced the dense pile of data on gene regulation which advanced computing methods might sort out for us.

By the end of the keynote address, I had mouse fever. I wanted to hear all about the things which these creatures could do, and it turned out that I had come to the right place. Over the next few days, I would hear about mutant mice who could run on a treadmill off the couch like they had trained for months. Mice who developed diabetes. Mice who could turn on their brown fat to alter their metabolism. And many of these mice could serve as their own experimental controls. They had mechanisms inserted in their genomes which could turn their genetic defects on and off in response to substances in their mouse chow.

I’ll admit, when I heard about designer mice and their custom mouse chow, I got a little side-tracked. I had been eager to get out of medicine for a while. It all seemed so futile, and even a bit of a sham. Knockout mice might have been the ticket.

Two incidents elevated that thought to conscious consideration. The first was sighting a booth devoted to mouse chow in the exhibit hall.

To understand the significance of the chow booth, one must understand what the exhibit hall is all about. There is an exhibit hall at every conference. They are huge and opulent sometimes, sometimes modest, but always staffed by beautiful, shiny people and stocked with treats, from lattes to foam-model pancreases. Brands like Coach or Louis V. would feel at home amongst the booths.

Giant pharmaceutical companies ruled the hall, and the mouse kibble guys were right there in the mix. If mouse chow could buy an exhibit booth, the mice themselves must be golden.

The second incident was a conversation overheard in the poster hall.

The poster hall is a huge open space with row upon row of cork boards. Researchers pin up posters with summaries of their investigations on the boards, and attendees walk up and down the rows soaking in the knowledge. Usually there is a clearing in the middle with a nest of round banquet tables where everyone can go to take a break, chat and have a cup of pharma coffee. That’s where I sat while my wife presented her poster. I did not sit randomly.

As I walked up on the tables, I spotted a fat man in a plaid shirt and a yarmulke leaning in to say something to a thin, swarthy, bearded companion wearing a dark olive sport coat and a gold medallion. I needed in on that conversation, so I settled in the chair next to them, and swirled my coffee thoughtfully. Imagine my surprise as I picked up on the subject of their conspiracy.

“Yes,” said the fat man, ” I have been trying to find some of those mice. I need them to finish my work, but you can’t find them anywhere.”

“Yes,” echoed his friend, “those mice are nowhere to be found.”

“The closest I came,” the fat man continued, “was this Korean lady in San Fransisco. She said she had some, even said she would send me a few. But she never came through, and now I can’t get a hold of her anymore.”

The mice must be golden.

But my dreams of becoming a mouse Baron were short-lived. Upon further investigation, I found that genetically altered mice did not thrive. It was hard enough to get them past the embryonic stage. Once they could breathe on their own, they often required special conditions and diets just to survive. Worst of all, most of the really good mice had been patented. You bought the limited rights to a strain of mice when you bought the animals themselves. The patent system was the impetus for the black market discussion in the poster hall. You could trade for mice underground and avoid some costs, at the risk of incurring the wrath of the mouse factory lawyers after publication.

Despite the disappointment on economic grounds, I left the conference optimistic. I still had the image of all those colored bars from Dr. Collins’ slide in my head. Each one was a gene which a mouse model could exemplify, and therefore each one was potentially a druggable target. We had this. It was just a matter of time, and mice.

On my way to work, I have some time to think, though not too deeply. I leave early to beat the traffic, but I never do. Most commutes demand constant attention to collision avoidance. The situation is unfortunate, because the commute is the only time to think. Once work starts, I am behind. Someone constantly needs something from me to satisfy someone else who needs something from them, etc.. My workplace is carefully structured to facilitate this cycle. If I need to communicate with someone, odds are that I can lean over to one side and speak to them directly. Otherwise, my computer contains a messaging system which will pop in on whoever I need to inform or interrogate. Patient rooms cluster around my workstation, so I never need to walk more than 6 steps. However, patient contact occupies only a minor portion of my time. Most of the day is passed on the computer and the phone, addressing questions, requests and lab results. At the end of the day the freeway awaits again. By the time I get home, I am burned out and may or may not have it in me to do some physical training and watch television before retiring to get up and do it all again the next morning.

As luck would have it, traffic was light on the first day back from New Orleans. As I drove, I dreamed of druggable targets; Dr. Collins’ slides with the colored bars swam before me. Most of my patients were already on carefully targeted medications, but reaching down into the genome would ramp up medication effectiveness by orders of magnitude. Yet, not all my thoughts were so happy. Other images kept popping into my head, unbidden. I saw other colored slides, from another lecture by another renowned researcher. They were Dr. Brawley’s slides on the geographic and socioeconomic correlates of life expectancy and the epidemiology of conditions like obesity, cancer and diabetes. I could not banish those intrusive images, and by the time I was walking across the clinic parking lot, my mood had deteriorated.

I made it through the day, and finally got to resume my train of thought as I walked back to the car to drive home. I thought about gene targets and Dr. Brawley’s maps again. Then thoughts of one of the day’s patients joined the fray. She was very overweight, and had the metabolic problems that went with excess adipose tissue. She was on targeted therapy for her diabetes in the form of a monoclonal antibody directed at a counter-regulatory hormone receptor. It was the best science had to offer, but she often missed her doses. She had 2 jobs and no car, so she was up early and home late, and she simply forgot her meds sometimes. She set an alarm, but often could not attend to it, or forgot to reset it. We did not even discuss diet and exercise. She lived on a busy street with non-contiguous sidewalks, had no money for a gym, and no time to travel to a safe park. She could not cook, because she had grown up on packaged foods. In any case, she had grown too heavy by now. Her knees had given out under the weight. She could only mobilize fat stores in the face of severe calorie restriction. To reclaim  her life, assuming that was our aim, she would need two joint replacements and a gastric bypass.

I began to re-experience the rising panic which I had felt at the end of her appointment. Dr. Collins & Co. had let me down; I was not armed for this struggle, nor would I be. I stopped to take a breath and get my bearings. The parking lot was nearly empty. A bad smell rose from a nearby drainage grate, and a noise like water flowing.

I imagined that the noise might be something else. Maybe, instead of waste water, it was all those knockout mice, rising through the  sewers from the depths of the New Orleans convention center where the disappointments of Katrina had flowed down to bring the little fellows back, like a time-delayed Ghost Dance. The mice were coming with their little spectral incisors primed to clip down the cages, the labs, the chow booth, the convention center, and all the rest in a massive, surgical revision. I became convinced that the sound was the mice coming. It had to be. It was the only way that the knockout mice could save us.

mouse

 

 

 

 

Advertisements
Tagged , , , , , , , , , , , ,

The Problem with Pain

My gaze swung between the man on the exam table and the radiograph displayed on the lightbox. He must have sensed a problem.

“What?” he asked.

What indeed. The film basically showed his shoulder blade broken in two.

“When did this happen?” I inquired. He had already told me once; I just needed to be sure that I’d heard it correctly.

“Yesterday afternoon,” he said, ” right after lunch.”

“And why did you wait until this afternoon to come in?’

“Well, I’m here mostly to get my wife off my back. If it was up to me, I wouldn’t have come in, but she thought it might be serious or something, because I tossed and turned last night.”

“Well,” I told him, “It is not a surgical problem, but it is a bad injury. You got lucky.”

After a moment’s reflection I added, “Didn’t that hurt?”

“Kind of,” he laughed, “But it eased up pretty quick.”

“Do you need any pain medication?” I asked.

“Oh, no,” he demurred, “Tylenol is doing fine for it.”

After a few more pleasantries, the man got up, walked out of my office, got in his car and drove back to work. Watching him wince slightly as he turned out of the parking lot, I couldn’t help but think of the patient before him – a fellow with no history of serious injury, a normal MRI of the lumbar spine, and disabling back pain.

The man with the back pain had wanted pain medication. I’d had to talk him out of it, which was a difficult task in that era. Because it was the era before the opioid crisis, when we were in the midst of a pain crisis, according to the medical authorities. Clinicians were directed to take everyone’s pain level the same way that we took their temperature, and to treat the abnormalities discovered by our measurements.

For those with eyes to see, the notion behind pathologizing pain was misguided, at least. The whole scheme rested on the idea that pain was simply activity in the neuronal substrate. Change the activity pattern, by activating opiate receptors, for example, and you get rid of the pain.

I am not being very charitable in my description, but I am being as charitable as I need to be. There are more nuanced depictions, which leaven the mix with talk of psychological context and so on, but the same suppressed premise lurks beneath them all. It is this: a chain of causal events ‘add up’ to pain, and that is just what pain is. X+Y+Z = Pain. But the necessity of such arithmetic has been in doubt even before Hume laid its troubles out so nicely for us Westerners.

Breaking down a phenomenon gives you its pieces, but does not grant commutativity. Activating opiate receptors does not reshape their owner’s pain experience according to a fixed script. Receptor activity is part of the description of a painful experience, along with psychological context, and personal history. Yet there is no prior necessity – necessity by law, rather than necessity in fact. We did not make the distinction.

Secure in our estimation of the relationship between the neuronal substrate and the pain experience, we went after opiate receptors like we go after splinters. Our efforts did not force anyone’s pain experience into a box, but we gave everyone who we treated a new pain experience. Sometimes it suited them better; sometimes it suited them worse. Many, many times it settled in the center of their psyches and they fell into orbit around it.

Our engagement with the epidemic of untreated pain predictably ended in chaos. Now we need to extricate ourselves, and what do we turn to but the tool already in hand.

Instead of the reduction to type, we have rebuilt our story of pain, revising our reduction on the basis of the same mistake. Receptors pertain to behaviors – in the neuronal substrate, and so in the psychology, and so in the organism – but pain is a byproduct of the behavioral mechanism. It is an epiphenomenon. Chronic experiencers need counselling, to convince them that the pain is ineffectual, and therefore not real, at least not in any serious way.

Unfortunately, I get to participate in this second shot at commutative reduction, too. It will go just as well as the first.

 

Tagged , , , , , , , , , , , ,

Cult of the Range-Fed Turtles

When my best childhood friend grew up, he decided to become an archaeologist. During his graduate training, he was in charge of  a dig in the Mississippi river valley which unearthed an odd structure. In the midst of the native people’s dwellings, was found a circular enclosure made of closely spaced wooden posts and containing a large pile of turtle shells. The undergraduates were eager to speculate about the purpose of the structure, but my friend cautioned them against it.

“We can’t be sure of its use,” he said”, and we can’t just guess based on what we might use an enclosure like that for today. We can’t just assume they were running a turtle ranch here. Why would they do that with a river full of turtles just a quarter-mile away? We have to put it in context of the surrounding village and the environment of the time, look for other examples and see if there are any modern structural analogs. Then we can make a guess, but it will still just be a guess.”

The next day the professor in charge of the dig came around on a rare site visit to see how things were proceeding. The students were eager to show him the mysterious ring of posts with its pile of shells.

Upon seeing their find, the professor remarked without hesitation, “Huh, must have been a turtle pen,” and promptly resumed his walking tour of the dig.

I don’t know if archaeology has an excuse for this kind of thinking, but medicine does:

Life is short. The art is long. Experience is difficult.

– Hippocrates

We can be forgiven for resorting to teleological assumptions now and again in medicine. With limited time and incomplete information, we must sometimes act on hypotheses which attribute function to structure and purpose to processes. Lucky for us, there’s plenty of slop in the system, so even if we’re wrong at the start, we usually get a second chance. We are trying to get away from teleology, though. “Evidence based medicine” and “scientific medicine” are the names that we have given that effort.

We are trying to get away from teleology because we have been burned by it. We thought that the body made pus to fight off bacterial infections, so for years, when we saw people with respiratory illness cough up phlegm with pus in it, we gave them antibacterial medications. We were wrong, not just about the purpose of pus, but in attributing a purpose to pus. Again, it was an understandable mistake, given the long history of debate regarding the merits of pus. Was it a good sign, or a bad one? Should we encourage or discourage its formation? It turns out we shouldn’t have been focusing on the pus at all, but on    the outcome of our purposeful intervention in the underlying process that produces the pus.

Purposeful results and final causes apply prospectively to human endeavors alone, and even there it’s often difficult to tell whether, when our actions are associated with the desired result, the outcome is due to our actions or simply due to fortuitous circumstances. Applied retrospectively or to processes and structures beyond our control, teleology is a sure mistake.

When we assign an endpoint to a process, we presume causation and correlation must be proven. Humans are notoriously bad at that. In systems which we can’t duplicate or control, we can always tell a causal story (I’m looking at you evolutionary psychology, intelligent design, cosmological fine tuning). But those stories are just interesting rationalizations, sharing the merits of a fairy tale in that they reveal more about us than the subject matter. Our fairy tales are harmless when they are about the universe, the origin of life, turtle ranches or anything else beyond our control. When we tell teleological stories about processes we do seek to influence (and can) we court tragedy.

The practice of bleeding was based on one such tale: the story of homeostasis. We still tell it today, but we tell it as metaphor instead of fact. The story is based on the simple observation that, when a person becomes ill, they go through a series of changes in their physical state which ultimately ends in either the restoration of their previous state, or death. Having observed other systems, the Greeks thought that the process of illness looked like a disequilibrium. Having observed associated changes in fluids which emanated from the body, they attributed the disequilibrium to an imbalance in those fluids. We can hardly blame them for the limits of their observations. We can’t fault their hypothesis. However, we can fault their method.

They didn’t just postulate an imbalance in the humors as a cause of illness, they presumed a balance of the humors as a state the body sought. The difference in these two points of view is subtle, but crucial. If  the balance of fluids is seen as descriptive  then restoring health by balancing the fluids remains a working hypothesis. It admits that other factors may determine the observed equilibrium. It leaves open the possibility that the observed flux of humors is a secondary phenomenon. Most important, it leaves physiologic equilibrium as a simple description, instead of presuming that it is a purpose with causal powers.

Given a description and a working hypothesis, physicians would look at their efforts to balance a patient’s humors with a critical eye. As a teleological assumption, with equilibrium as a “final cause” under Aristotle’s system, the idea creates an entirely different viewpoint. With  humoral balance rooted in the body’s design, variances in expected observations must be due to inadequate methods or incomplete knowledge of the humors. For this version of the “balancing the humors” hypothesis, failure is not an option.

Now, the ancient Greeks may have weathered this kind of assumption better than their heirs. They loved to fight with each other. In the face of inconsistent outcomes from humor-balancing interventions, they were likely to call Aristotle and Hippocrates idiots or just ignore the under-girding theory of causes altogether in favor of their own pet theory. Definitive statements naturally took a healthy beating in the Greeks’ intellectual environment. The Romans, and the Europeans who came after them, were much more pious.

As a result, no one questioned the teleological assumption, out of reverence for its sources, and the vital fluids persisted in medical thought owing largely to the idea of homeostasis by design. No matter how apparent the flaws in our understanding of the blood, bile and phlegm, they were somehow attached to the homeostatic goal of the body. As long as physicians saw that equilibrium as the body’s goal, they could reconcile any discrepant observations with the over-arching story and persist in practices such as bleeding. It fell to investigators outside of the medical profession to discover the secondary nature of the humors. Only then did the practices aimed at balancing the fluids truly begin to fade.

But long after bleeding and the balance of fluids fell by the wayside, the tale of homeostatic purpose continued to plague medical science. Physicians continued to view physiology as directed toward an end. For example  the heart was seen not to pump blood, but to be a pump. Therefore, medical students were instructed to never administer medications called beta-blockers to patients with heart failure.

Beta-blockers stick to proteins in the membranes of  heart cells called beta receptors, which normally bind adrenaline. Via the beta receptor proteins, adrenaline stimulates the heart to pump faster and with more force. In heart failure, the heart can’t contract forcefully or fast enough to keep up with the volume of blood returning to it from the veins. If the heart is a purpose-built pump, beta blockers should be anathema in the setting of heart failure. But in reality, when given to stabilized heart failure patients, beta blockers reduce long-term mortality by about one-third.

We don’t yet know exactly how these medicines achieve such a feat. We do know why they are not inevitably detrimental in heart failure. It is because the heart pumps, but it is not a purpose-built pump. The heart is instead a group of cells which inhabits a specialized niche in a system of many cells all with complimentary and competing characteristics, existing in a state of equilibrium which, in deference to tradition, we call homeostasis.

Our physiology doesn’t try to maintain homeostasis any more than erosion tries to form a natural arch. The arch forms (rather than crumbling like the sides of a stream-bed) because it is geometrically stable given the geology. The arch persists because it is geometrically stable, and so we frequently see natural arches where the climate and geology allow. Nobody marvels at this, speculating about a conspiracy between sandstone and weather patterns. Then again, few people have an emotional stake in natural arches. The same is true of our physiology, minus the low stakes. There is no overall homeostasis sensor or hormone in the body. There is no homeostasis conspiracy.

So, we have abandoned the notion of purpose in physiology, and that simple maneuver has allowed us to discover things like the survival benefit which beta blockers produce in heart failure. This move is the principle behind the randomized, controlled clinical trial. All along, it wasn’t ignorance holding us back, but the project of rationalizing our knowledge to traditionally understood, teleological models.

Of course, the questions driving evidence based medicine don’t start from nowhere. Scientific medicine asks questions based on the results of previous investigations and hypotheses derived from basic science discoveries regarding the components of physiology and their relationships. Some of these hypotheses are even most easily stated in terms of purpose. But those statements are now understood as metaphor, rather than bare fact.

Beyond the fecundity of this change in method, the move away from teleology finally brings some redemption for poor Hippocrates. Rather than using it as an excuse, we can understand his aphorism, “Life is short. The art is long. Experience is difficult “, properly again – as an admonition about method. Be skeptical. Remember that your viewpoint is limited. Watch out for overarching narratives. Good advice, and not just for medicine, but for all those turtle-ranch theorists out there (I’m looking at you intelligent design, cosmological fine tuning, evolutionary psychology…).

Tagged , , , ,

The Harder Problem

I have a purple shirt, or maybe it is royal blue. I was never in doubt about the color until my wife called it blue one day. Up until that point, I never even contemplated calling the shirt blue, or that there might be a difference between my perception of the shirt’s color and her’s.

Maybe there still is not a difference. Maybe our perceptions are the same and the words we use differ unnecessarily. If I look hard, though, I can see how she would call the shirt blue.

Her and my perceptions are almost certainly not the same, nor are anyone’s. The alternative – that people disagree about colors, and so much more, because our language is massively mistaken – seems too incredible. Shouldn’t we have ferreted out even the most minor issues by now? After all, we do so well at finding agreeable words for so many things, even in the realm of aesthetics.

Plus, there is a good explanation for the source of disagreement between me and my wife on my shirt’s color. If one tracks back how each of us learned to classify blue and purple experiences, there are substantial differences. And, those differences do not only effect our use of words; those differences also condition our purple and blue perceptions .

Yet there is another problem lurking. Even if I could magically take a snapshot of my brain at the moment in which I saw the shirt as purple, and show it to my wife, not as a map or photo, but as exactly the same state of affairs imposed upon her neurons, she could still differentiate it upon reflection. The brain state in question would always be her experience of my experience, rather than simply her experience. My experience of the shirt’s color cannot be captured, as mine, by means of physical reproduction.

One might ask, who cares? The upshot of our limitations is tolerable. Big truths may be a little counterfeit by implication, but we are accustomed to working with flawed notions already, and do fine by it. For example, Newtonian mechanics serves us beautifully, even if it is not ‘really true’.

Yet, we do not tolerate our flawed notions. An optimist would say that we are not satisfied with lesser things, and are constantly trying to improve our understanding. Our behavior suggests otherwise, however. We want big truths in principle, and the certainty, the reality, that comes along with them. In physics, we don’t just want quantum mechanics and relativity, we want a theory of everything. In ethics, we want good and evil, and duties to serve.

So, the hard problem does matter, because it is motivating. And, it moves us to a harder problem. We want things to be true which are not merely false, but which are incapable of being true or false. The idea of a concept not being truth-apt is slippery, so an illustration is in order.

Consider the case of Baby K. Baby K was born over two decades ago without a brain. Not only was she(?) born, she pulled off a feat which few anencephalics manage; she lived more than briefly. Or, she maintained a metabolism more than briefly, because her status as a living thing, much less a living human infant, was in question. She would never see a purple shirt, or a blue shirt, or have any experience at all. And since our personal experience is what we value above anything (what choice do we have, after all?) some people felt that a creature without experience and incapable of it was not truly alive, much less human.

Baby K’s mother disagreed. She felt that K was born of a human, exhibited some behaviors, had a heartbeat, and therefore fit into the human peg-hole, albeit imperfectly. K’s remarkable persistence owes to her mother’s insistence on aggressive medical interventions for K, based on K’s status as a human baby. For K’s mother, the rules of classification were categorical. There are Forms in the world, according to this school of thought, and the Forms suck their creatures in, even the most flawed copies.

When Baby K had trouble breathing, her mother took her to the ER and demanded that Baby K be saved, put on a ventilator, and nursed back to health in the ICU. But was health one of K’s capabilities? She needed saving, but for what, and from what? We could not ask K about any of this, ever, even in principle. As her physiology counted down to its end, what was there to distinguish this tick from the following tock, and so provide a basis for valuing more of the physiological process?

When K came in to the ER, the professionals on duty did not want to treat her. Since she was incapable of experience, she had nothing to value (there wasn’t even anyone there to value anything). Efforts to ‘help’ K were therefore empty. There was nothing to help with and no one to accept the helpful gesture.

Remarkably, some argued that further medical interventions merely prolonged K’s suffering. Perhaps they meant to say that further interventions caused the staff to suffer. More properly, futile actions degraded the integrity of the medical professions. We become what we practice, and if the medical professionals practiced service to the beating heart, then they rightfully feared that they would become servants to the beating heart.

The hospital also expressed concerns about the resources that K consumed. This argument was a utilitarian argument and failed in the usual fashion. If K did not occupy the ICU bed, the bed would not move to an under-served area, nor would the unexpended cost of K’s breathing tubes and procedures be converted into mosquito nets for children in malaria-afflicted territories. Values are not generally translatable, any more than their costs are portable.

But the missing cipher in the professionals’ calculation was K’s value to her mother. Someone did experience K’s physiology after all. To waive K’s value on that account was just as degrading as crass service to the beating heart. If the medical professions seek to serve health, and health is function, then the milieu is everything. It was a mistake to consider K’s value on the basis of K’s intrinsic capacity for experience, just as much as it was a mistake to think that the ventilator was saving K herself from or for anything. However mistaken she was about Forms and their efficacy, K’s mother valued K’s beating heart in a consistent way. Harm would come to the mother from K’s heart stopping. It would be the same sort of harm – loss of experience and the possibility of experience – to which the professionals referred in their assessment of K’s lack of value.

All along, the players in the Baby K saga evaluated her with standards that did not apply – that were not truth-apt. It was never the case that Baby K was human or not, alive or not. Her case nicely demonstrates the nature of the harder problem. Our standards – good, evil, human, matter, energy, mine, yours, blue, purple – are not stand-alone things. They are made of their circumstances (our circumstances). Without a doubt, the standards serve us well, since our circumstances are necessarily shared. If the standards refer to the specifics, and the specifics are near enough alike, it’s just good fudging to defer to the standards. It is easy to forget that the standards defer to their instances. And we are motivated to forget, because we value our experience and we value our standards, and we are prone to equate the two.

 

 

 

Tagged , , , , , , , , ,

Dr. Van Helsing Does Not Practice Primary Prevention

As recommendations for treatment of hyperlipidemia become broader and more generic, drifting toward the poly-pill conclusion, I can’t help but think of Dr. Van Helsing’s predicament in Dracula. In the story, though he has information which suggests the possibility of primary prevention, he practices secondary prevention. It is only after the symptoms appear – Lucy’s mysterious anemia and the rash of similar cases following her death – that the doctor suggests putting garlic around the windows. He has to wait. He’s in a story, so he knows the horrible truth all along, but he can’t reveal it without his patients sending him packing. Every doctor understands Van Helsing’s predicament. Few can see his patients’ logic however. It is one thing to indulge a crazy old man’s belief in vampires. It is quite another to indulge a crazy old man’s belief that a vampire has moved into the old mansion down the street and has begun to prey upon the household.
When doctors tell patients to treat public health problems, like cardiovascular disease prevention, on an individual basis, the patients take it as if they were being asked to put garlic around their windows because there have been vampire sightings in their neighborhood. They are slightly incredulous. And, the patients are right.
If we medical professionals are to treat asymptomatic individuals based on a 10 year risk calculated from epidemiologic data, for a disease which they have may or may not have started to develop, we must be honest with them. We have to admit that medication is the best that we can do, ask for their help, as a group, and then make it easy for them to help. Doctors don’t like to treat populations, though. Individualized care and patient centered care are the current watch words. But the greatest successes of medical science have been the opposite sort of effort. Nobody thinks that we should stop immunizing people for pertussis and move to an individualized prevention program with regular swabs for the pertussis bacteria and antibiotics for every runny nose. The approach is ostensibly patient centered, and it really is in a way, just like Dracula’s interest in Lucy and Mina is patient centered. Looking down from the established high ground, it’s easy to recognize the shift to an individualized strategy for preventing whooping cough as impractical and myopic. Medical professionals are clever enough to avoid bad moves from the general to the specific. However, decisions to move from a dysfunctional individualized program to a population based program can trip up anyone, even though the determining factors are the same.
The problem is Van Helsing’s problem. At the level of the vampire hunter’s interest, garlic around the windows is garlic around the windows. He’s like Dracula that way, for whom young ladies full of blood are young ladies full of blood. Dracula and Van Helsing are at risk of availability bias, cognitively and practically, as are all the physicians with lipid profiles, risk calculators and statistical correlations at their fingertips. There is a insidious, vampiric class of maneuver from population-based conclusions to individualized care. But the patients’ motivations lie outside of the action’s focus, and that focus is therefore myopic. It does matter to patients whether the doctor is asking them to deck the sills in order to cut down on the incidence of vampire attacks or because they should fear the vampire staring at them through the window. The latter request involves adopting an astringent manner of thought and behavior, the stuff of anxiety disorders. The former is an appeal to solidarity and public safety. We shouldn’t be surprised when the same people we’ve been instructing to fear the vampire outside their window come in demanding that we do something about the pale figure lurking behind their cough, in their prostate, or under their nipple. Having ceded the high ground, we’ve no credible response.

Tagged , , , , , , ,

Cult of the Range-Fed Turtles

When my best childhood friend grew up, he decided to become an archaeologist. During his graduate training, he was in charge of  a dig in the Mississippi river valley which unearthed an odd structure. In the midst of the native people’s dwellings, was found a circular enclosure made of closely spaced wooden posts and containing a large pile of turtle shells. The undergraduates were eager to speculate about the purpose of the structure, but my friend cautioned them against it.

“We can’t be sure of its use,” he said”, and we can’t just guess based on what we might use an enclosure like that for today. We can’t just assume they were running a turtle ranch here. Why would they do that with a river full of turtles just a quarter-mile away? We have to put it in context of the surrounding village and the environment of the time, look for other examples and see if there are any modern structural analogs. Then we can make a guess, but it will still just be a guess.”

The next day the professor in charge of the dig came around on a rare site visit to see how things were proceeding. The students were eager to show him the mysterious ring of posts with its pile of shells.

Upon seeing their find, the professor remarked without hesitation, “Huh, must have been a turtle pen,” and promptly resumed his walking tour of the dig.

I don’t know if archaeology has an excuse for this kind of thinking, but medicine does:

Life is short. The art is long. Experience is difficult.

– Hippocrates

We can be forgiven for resorting to teleological assumptions now and again in medicine. With limited time and incomplete information, we must sometimes act on hypotheses which attribute function to structure and purpose to processes. Lucky for us, there’s plenty of slop in the system, so even if we’re wrong at the start, we usually get a second chance. We are trying to get away from teleology, though. “Evidence based medicine” and “scientific medicine” are the names that we have given that effort.

We are trying to get away from teleology because we have been burned by it. We thought that the body made pus to fight off bacterial infections, so for years, when we saw people with respiratory illness cough up phlegm with pus in it, we gave them antibacterial medications. We were wrong, not just about the purpose of pus, but in attributing a purpose to pus. Again, it was an understandable mistake, given the long history of debate regarding the merits of pus. Was it a good sign, or a bad one? Should we encourage or discourage its formation? It turns out we shouldn’t have been focusing on the pus at all, but on    the outcome of our purposeful intervention in the underlying process that produces the pus.

Purposeful results and final causes apply prospectively to human endeavors alone, and even there it’s often difficult to tell whether, when our actions are associated with the desired result, the outcome is due to our actions or simply due to fortuitous circumstances. Applied retrospectively or to processes and structures beyond our control, teleology is a sure mistake.

When we assign an endpoint to a process, we presume causation and correlation must be proven. Humans are notoriously bad at that. In systems which we can’t duplicate or control, we can always tell a causal story (I’m looking at you evolutionary psychology, intelligent design, cosmological fine tuning). But those stories are just interesting rationalizations, sharing the merits of a fairy tale in that they reveal more about us than the subject matter. Our fairy tales are harmless when they are about the universe, the origin of life, turtle ranches or anything else beyond our control. When we tell teleological stories about processes we do seek to influence (and can) we court tragedy.

The practice of bleeding was based on one such tale: the story of homeostasis. We still tell it today, but we tell it as metaphor instead of fact. The story is based on the simple observation that, when a person becomes ill, they go through a series of changes in their physical state which ultimately ends in either the restoration of their previous state, or death. Having observed other systems, the Greeks thought that the process of illness looked like a disequilibrium. Having observed associated changes in fluids which emanated from the body, they attributed the disequilibrium to an imbalance in those fluids. We can hardly blame them for the limits of their observations. We can’t fault their hypothesis. However, we can fault their method.

They didn’t just postulate an imbalance in the humors as a cause of illness, they presumed a balance of the humors as a state the body sought. The difference in these two points of view is subtle, but crucial. If  the balance of fluids is seen as descriptive  then restoring health by balancing the fluids remains a working hypothesis. It admits that other factors may determine the observed equilibrium. It leaves open the possibility that the observed flux of humors is a secondary phenomenon. Most important, it leaves physiologic equilibrium as a simple description, instead of presuming that it is a purpose with causal powers.

Given a description and a working hypothesis, physicians would look at their efforts to balance a patient’s humors with a critical eye. As a teleological assumption, with equilibrium as a “final cause” under Aristotle’s system, the idea creates an entirely different viewpoint. With  humoral balance rooted in the body’s design, variances in expected observations must be due to inadequate methods or incomplete knowledge of the humors. For this version of the “balancing the humors” hypothesis, failure is not an option.

Now, the ancient Greeks may have weathered this kind of assumption better than their heirs. They loved to fight with each other. In the face of inconsistent outcomes from humor-balancing interventions, they were likely to call Aristotle and Hippocrates idiots or just ignore the under-girding theory of causes altogether in favor of their own pet theory. Definitive statements naturally took a healthy beating in the Greeks’ intellectual environment. The Romans, and the Europeans who came after them, were much more pious.

As a result, no one questioned the teleological assumption, out of reverence for its sources, and the vital fluids persisted in medical thought owing largely to the idea of homeostasis by design. No matter how apparent the flaws in our understanding of the blood, bile and phlegm, they were somehow attached to the homeostatic goal of the body. As long as physicians saw that equilibrium as the body’s goal, they could reconcile any discrepant observations with the over-arching story and persist in practices such as bleeding. It fell to investigators outside of the medical profession to discover the secondary nature of the humors. Only then did the practices aimed at balancing the fluids truly begin to fade.

But long after bleeding and the balance of fluids fell by the wayside, the tale of homeostatic purpose continued to plague medical science. Physicians continued to view physiology as directed toward an end. For example  the heart was seen not to pump blood, but to be a pump. Therefore, medical students were instructed to never administer medications called beta-blockers to patients with heart failure.

Beta-blockers stick to proteins in the membranes of  heart cells called beta receptors, which normally bind adrenaline. Via the beta receptor proteins, adrenaline stimulates the heart to pump faster and with more force. In heart failure, the heart can’t contract forcefully or fast enough to keep up with the volume of blood returning to it from the veins. If the heart is a purpose-built pump, beta blockers should be anathema in the setting of heart failure. But in reality, when given to stabilized heart failure patients, beta blockers reduce long-term mortality by about one-third.

We don’t yet know exactly how these medicines achieve such a feat. We do know why they are not inevitably detrimental in heart failure. It is because the heart pumps, but it is not a purpose-built pump. The heart is instead a group of cells which inhabits a specialized niche in a system of many cells all with complimentary and competing characteristics, existing in a state of equilibrium which, in deference to tradition, we call homeostasis.

Our physiology doesn’t try to maintain homeostasis any more than erosion tries to form a natural arch. The arch forms (rather than crumbling like the sides of a stream-bed) because it is geometrically stable given the geology. The arch persists because it is geometrically stable, and so we frequently see natural arches where the climate and geology allow. Nobody marvels at this, speculating about a conspiracy between sandstone and weather patterns. Then again, few people have an emotional stake in natural arches. The same is true of our physiology, minus the low stakes. There is no overall homeostasis sensor or hormone in the body. There is no homeostasis conspiracy.

So, we have abandoned the notion of purpose in physiology, and that simple maneuver has allowed us to discover things like the survival benefit which beta blockers produce in heart failure. This move is the principle behind the randomized, controlled clinical trial. All along, it wasn’t ignorance holding us back, but the project of rationalizing our knowledge to traditionally understood, teleological models.

Of course, the questions driving evidence based medicine don’t start from nowhere. Scientific medicine asks questions based on the results of previous investigations and hypotheses derived from basic science discoveries regarding the components of physiology and their relationships. Some of these hypotheses are even most easily stated in terms of purpose. But those statements are now understood as metaphor, rather than bare fact.

Beyond the fecundity of this change in method, the move away from teleology finally brings some redemption for poor Hippocrates. Rather than using it as an excuse, we can understand his aphorism, “Life is short. The art is long. Experience is difficult “, properly again – as an admonition about method. Be skeptical. Remember that your viewpoint is limited. Watch out for overarching narratives. Good advice, and not just for medicine, but for all those turtle-ranch theorists out there (I’m looking at you intelligent design, cosmological fine tuning, evolutionary psychology…).

Tagged ,

Carnival of Adverse Selection

A Canadian friend once told me that he did not understand the American political system and asked if I could explain it to him. I told him that it was basically an exercise in pest management. On the one hand you have your smarmy rats (Democratic politicians) and on the other you have your vicious rats (Republican politicians). The first kind you don’t even want near you, the second kind you just want to stomp. Either way you’ve got an intractable rat problem, so mostly you just try to ignore them as best you can and get on with your life.

Sometimes though, they crawl across the kitchen counter in broad daylight and then you have to pay attention to them. That happened to me during the last Presidential debate. I was doing my best to ignore it, but we have a radio in the garage with a power switch stuck in the ‘on’ position and the debate was playing in the background. I had it successfully tuned out until they started talking about health care and Romney, who’s turning out to be a particularly nasty little ankle-biter, came with the crazy talk.

Here’s what he wants to do about health insurance:

  • Block grant Medicaid and other payments to states, limit federal standards and requirements on both private insurance and Medicaid coverage. The state can structure a cost-share program however it wants?  It can still shift costs to the Emergency Rooms of Medicare-participating hospitals and to the Medicaid programs of richer states (a kind of internal ‘self deportation’ which already happens to a limited extent)? I can’t imagine what the states might do? These changes are supposed to lead to innovation, and they will – just more the sort of innovation that financial system deregulation allowed.
  • Unshackle Health Savings Accounts by eliminating the minimum deduction requirement and allowing people to use the account funds to pay premiums. HSA’s are a nice product for a very limited income range. If you make too much money or too little to make the tax savings worthwhile, a HSA makes no sense. The proposed changes won’t change that. So, why make the changes? Hang on a minute, I’ll get to that.
  • Allow consumers to purchase insurance across state lines. Recall this is the now minimally regulated insurance product. Watch the insurance companies gobble each other up as they try to recruit all those newly available good risks. Watch high risk people get filtered out of the broader  insurance pool as the generous benefit plans become increasingly burdened with these individuals, and the prices for those plans go up and up, in turn prompting lower risk people to leave for cheaper, less generous benefit plans. Will Romney & Co. adequately fund a reinsurance plan to keep this from happening? Not to worry, people with chronic problems can still go to the ER, right? People can preemptively accomplish this adverse selection themselves via purchasing pools, right?
  • Medicare will become a premium support program. The premium support and benefit requirements will be fixed at the current levels in Medicare. If costs go up, the market will determine how people make up the difference. And in time, like gravity takes care of shoddy construction projects (who really needs architects or building codes), the market will take care of things by channeling the high risk people into the more generous plans (Medicare), driving those plans’ costs out of sight and eventually, driving those plans and high risk  people out of the market. I can almost hear the invisible hand slapping – see adverse selection and cost shifting above. (It’s actually worse than that – Medicare has a normative effect that goes beyond its simple economic effects but that is a story too long and tangential for the moment.)

So, why make the changes if they entail all these predictable distortions? Free market fundamentalism is the answer. Markets aren’t a highly effective tool for these guys, they are a moral imperative. So in their view, markets must be good for every application. Just set up a market and have faith; it will solve any problem. Regulation and critical analysis aren’t caution, they’re apostacy. I’d usually ignore this crap, like I ignore people praying for rain, but this is more like praying that your kid gets better from leukemia in lieu of consulting an oncologist. I feel like I’ve at least got to say something.

So, for all who wondered what could be worse than Obamacare – it’s this happy horse shit. These two rats are scampering across the counter in broad daylight with this mess, and they need stomping, (metaphorically of course).

Tagged , , , , ,

Marketing a Pig in a Poke

Everyone knows better than to buy a pig in a poke, so selling one ought to be hard. It happens everyday in clinics and hospitals, though. Marketing is the key. The seller just has to convince the buyer that nobody really knows what’s in the bag, and that it might be really good. Fortunately, the task is easy for healthcare providers, because it’s just’ telling the truth. Much of the time, both parties can take a good guess at the bag’s contents. Sometimes neither is certain. In any case, a rational price is difficult to determine.

That’s why our current system uses baseline administrative pricing. There may be equally bad ways of pricing healthcare services, but there probably aren’t any better ways. At least this way, prices are based on an educated guess about what is in each bag.

Market pricing is an alternative method. It would give very good prices for squealing bags with pig-shaped lumps in them – things like Botox treatments and laser vision correction. Prices for bags with more amorphous lumps, containing things like cholesterol medicines, blood pressure medicines and cancer screening tests, not so much. The prices for those bags which, in livestock terms, could hold a pedigreed piglet or a skunk, would vary based on the buyers’ fears, hopes and disposable income. It’s a recipe for very good, cheap Botox treatments, and very good, cheap cardiac bypass surgeries and kidney transplants. It might not result in an efficient allocation of resources, but it would present an excellent marketing opportunity for those willing to prey on others’ hopes and fears.

Tagged ,
Advertisements