Laura, the sleeve worked before anyone understood why, and that's the part that should unsettle us more than it does. It began as the first stage of a two-stage operation, the part that wasn't expected to be the whole answer. Then it started behaving like one. Patients did well enough that some never returned for the second surgery. The operation was right for years while the explanations attached to it, restriction, malabsorption, plumbing, were wrong or at least too small.
Which inverts what we usually mean by understanding a treatment. We tend to treat mechanism as what licenses the intervention. Here the intervention was changing diabetes within days while the explanation on the chart was not the real mechanism. The wrong theory did not blunt the right result.
It makes me wonder how much of current practice is in the same position, working for reasons we're describing incorrectly right now, and will only correct in hindsight. The ghrelin story has a tidy ending because we found the hormone. The unsettling version is the operation that works today whose real reason we haven't stumbled on yet, and won't, until something forces us to look.
The sleeve gastrectomy was indeed originally performed as step 1 of the duodenal switch, until patients experienced weight loss outcomes that defied the assumed mechanism of restriction. Similar to the (then) inexplicable observation that some bypass patients no longer required insulin within a day of the operation, the sleeve challenged the traditional explanations for weight loss after bariatric surgery.
The ghrelin story is reasonably tidy, because we found the hormone—although it’s likely we still don’t have a complete understanding of the hormonal drivers of hunger and metabolism or the mechanisms of many bariatric operations. But the ghrelin story is also not unique! Rather, this process—an unexplained observation launching a reassessment and correction of understanding—is how medical progress happens. How progress happens in any field.
There are stories that mirror the sleeve, where something worked before we understood the mechanism. As far back as Semmelweis, who could prove with his outcomes that chlorine handwashing prevented childbed fever but couldn’t explain why— and attributed his success to “invisible cadaver particles.” There are also stories where our lack of understanding has real, immediate consequences for patients. Like Kocher, who made thyroid surgery technically possible before the word “hormone” had ever been used. His ignorance of the thyroid gland’s function led to horrific side effects: and his attention to, and investigation of, unexplained outcomes would eventually lead to the discovery of the hormone and a much more profound and accurate understanding of physiology.
You ask, appropriately: how much of current practice sits at this nexus. What current operations work today for reasons we don’t understand, or are causing bad outcomes we don’t yet appreciate? How much, in short, do we not yet know? The answer is: a lot. It can be unsettling to acknowledge, in historical examples or current ones, the limits of our knowledge. It also makes the people who acted despite the uncertainty, and kept looking for evidence that they might be wrong, more admirable rather than less. Because acting on incomplete knowledge isn’t a moral failure, but refusing to examine contradictory evidence is. It’s a standard to strive for, knowing that we still need to act before we have complete understanding, and that tomorrow’s observations may challenge the choices of today.
Laura, I hadn’t thought of Kocher here. Thank you for bringing him in.
Your distinction between acting on incomplete knowledge and refusing contradictory evidence is exactly right, but it also made me wonder about the cases where no contradiction ever appears. Semmelweis had the mortality. The sleeve had patients who never needed stage two. In both, the intervention produced an anomaly loud enough to force a second look.
The more unsettling category may be the treatment that works for the wrong reason and produces nothing strange enough to investigate. No unexpected failure, no surprising benefit, no signal that the mechanism is too small. The success itself becomes camouflage.
Those may be the explanations we never correct, not because anyone refused the evidence, but because nothing ever told us there was evidence missing.
Laura, the sleeve worked before anyone understood why, and that's the part that should unsettle us more than it does. It began as the first stage of a two-stage operation, the part that wasn't expected to be the whole answer. Then it started behaving like one. Patients did well enough that some never returned for the second surgery. The operation was right for years while the explanations attached to it, restriction, malabsorption, plumbing, were wrong or at least too small.
Which inverts what we usually mean by understanding a treatment. We tend to treat mechanism as what licenses the intervention. Here the intervention was changing diabetes within days while the explanation on the chart was not the real mechanism. The wrong theory did not blunt the right result.
It makes me wonder how much of current practice is in the same position, working for reasons we're describing incorrectly right now, and will only correct in hindsight. The ghrelin story has a tidy ending because we found the hormone. The unsettling version is the operation that works today whose real reason we haven't stumbled on yet, and won't, until something forces us to look.
Thank you for reading, and for this comment.
The sleeve gastrectomy was indeed originally performed as step 1 of the duodenal switch, until patients experienced weight loss outcomes that defied the assumed mechanism of restriction. Similar to the (then) inexplicable observation that some bypass patients no longer required insulin within a day of the operation, the sleeve challenged the traditional explanations for weight loss after bariatric surgery.
The ghrelin story is reasonably tidy, because we found the hormone—although it’s likely we still don’t have a complete understanding of the hormonal drivers of hunger and metabolism or the mechanisms of many bariatric operations. But the ghrelin story is also not unique! Rather, this process—an unexplained observation launching a reassessment and correction of understanding—is how medical progress happens. How progress happens in any field.
There are stories that mirror the sleeve, where something worked before we understood the mechanism. As far back as Semmelweis, who could prove with his outcomes that chlorine handwashing prevented childbed fever but couldn’t explain why— and attributed his success to “invisible cadaver particles.” There are also stories where our lack of understanding has real, immediate consequences for patients. Like Kocher, who made thyroid surgery technically possible before the word “hormone” had ever been used. His ignorance of the thyroid gland’s function led to horrific side effects: and his attention to, and investigation of, unexplained outcomes would eventually lead to the discovery of the hormone and a much more profound and accurate understanding of physiology.
You ask, appropriately: how much of current practice sits at this nexus. What current operations work today for reasons we don’t understand, or are causing bad outcomes we don’t yet appreciate? How much, in short, do we not yet know? The answer is: a lot. It can be unsettling to acknowledge, in historical examples or current ones, the limits of our knowledge. It also makes the people who acted despite the uncertainty, and kept looking for evidence that they might be wrong, more admirable rather than less. Because acting on incomplete knowledge isn’t a moral failure, but refusing to examine contradictory evidence is. It’s a standard to strive for, knowing that we still need to act before we have complete understanding, and that tomorrow’s observations may challenge the choices of today.
https://anatomists.substack.com/p/right-for-the-wrong-reasons
https://anatomists.substack.com/p/dont-touch-the-thyroid
Laura, I hadn’t thought of Kocher here. Thank you for bringing him in.
Your distinction between acting on incomplete knowledge and refusing contradictory evidence is exactly right, but it also made me wonder about the cases where no contradiction ever appears. Semmelweis had the mortality. The sleeve had patients who never needed stage two. In both, the intervention produced an anomaly loud enough to force a second look.
The more unsettling category may be the treatment that works for the wrong reason and produces nothing strange enough to investigate. No unexpected failure, no surprising benefit, no signal that the mechanism is too small. The success itself becomes camouflage.
Those may be the explanations we never correct, not because anyone refused the evidence, but because nothing ever told us there was evidence missing.