Amazing. And shameful (for them.)
When I did my bio undergrad I was keenly aware our bodies are just scaled up molecular machines. I was hoping for a future where we'd grow MHC-neutral clonal bodies for organ harvesting.
Nope. We're in the stone age.
Clone humans. Cut off their brain stem during development. Turn off cephalization signals for good measure. Scale it up to industrial scale.
Research problems solved.
We'd have every study at our fingertips. We'd have organs and tissue and blood for everyone.
We could possibly even do whole head transplants and cure all non-blood, non-brain cancers.
But we're playing in the sand.
If you toss out the old rule book and provide unlimited funding, it can be made to work.
Our bodies are bigger machines made of lots of little machines.
Our minds or conscious egos or "souls" are the neurotransmitter and activation activity of the connectome and all of its cells and synaptic weights and metabolic activity. They're our lived experiences for as long as our brains can function. Minds experience and produce wonderful things.
If you divorce the body from the mind, there is no "person". Just a very complicated machine. A very valuable machine full of parts.
A human body in a vegetative state is not a person. It's a dormant machine. People may have emotional attachment to that vestige, but it is no longer capable of being a person. It is not a person.
We use brain dead humans for organ transplant all the time. If you understand the premise, then it isn't that far-fetched that we might grow vegetative humans in a lab for medical use and research.
Bodies that never have brains can never become persons. They're no different from plants.
There is decent experimental evidence to demonstrate that we are more than gene expression and the machine analogy you insist on is not a good one for understanding biological systems - see work by Michael Levin, as example.
There is a wider paradigmatic shift underway that moves from thinking about parts to processes. This refocus on relations rather than objects is very important and, for biological systems, points to a fundamentally social/collective aspect to their nature.
The machine metaphor also fails when you can no longer explain how the machine works. This is true in many areas of medicine (e.g. anasthesia) and, while we continue to believe (sometimes with enormous zeal) in the concepts that helped us in the past, we cling to them at the cost of building better understanding.
What you say isn't "wrong", but it is too limited to be a useful guide in asking new questions about things like immunotherapy treatments.
There is a difference between "reasonable guardrails" and suffocating progress until it's nearly impossible barring Herculean efforts by multibillion dollar entities. It cannot be understated how badly the current bureaucracy has destroyed medical progress.
We are seeing the same problem with nuclear overregulation result in worse outcomes and more deaths for people globally.
There is real suffering and a human cost, measurable in lives, to slowing down progress - just as there is one for reckless progress.
The medical journals are filled with studies that "should have worked" and didn't.
Heck, there are a ton of studies that "should have worked" that were harmful.
So much for "we're just scaled up molecular machines".
> the process has become more important than the problem you’re trying to solve.
We have a word for this, which roughly translates to "rule of paperwork". Bureaucracy.
Do I keep going or is the IRB approval process clearer now? There is a reason it exists.
We're talking about a factor that no one has previously had reason to consider important.
Of course, I don't know hard it truly is to undertake a study. I have to imagine for something like this you could write up a basic study protocol in fairly short order.
> How do you ensure you collected enough of a sample of a general population to make your study representative?
You don’t need to. This would be a pilot study to check whether there’s maybe a there there before you do it larger scale to measure predictive power at population level.
> Do I keep going or is the IRB approval process clearer now? There is a reason it exists.
I think you’re completely failing to engage with the argument that this particular case about time shifting delivery of a drug should not need meaningful IRB engagement other than “I’d like to change the time I deliver the drug for 2 more patients because we had one patient respond positively and this isn’t believed to be a factor” “ok cool yup”.
You’ve jumped from no IRB to full IRB without considering the context of the problem being solved which is why I said when the process becomes the goal vs the problem you’re trying to solve - you’re imaging the worst and most complicated situations possible for a case that would never demand it.
> The IRB is often in place not to stop positive outcomes, but to reduce negative ones.
Research can literally be IRB exempt if it provides minimal or no risk to patients which is literally what this is. Even if you put this in the "minimal risk" category which would be extreme that's still minimal IRB oversight and approval takes ~1-3 weeks.
You're imagining IRB is something it's not even intended to be and then saying it's a reasonable bottleneck in general because of real problems it prevents and thus justified for this specific experiment (where it wouldn't be relevant).
This is top to bottom a failure to follow up - doctor's are overworked & fail to follow up on potential research results because they act more like mechanics.
There are an endless number of parameters in medicine that can be fiddled with. If an N=1 sample were enough to convince you, all sorts of garbage would meet that pattern.
No, it would be more accurate to say "any ethicist worth his salt would argue: don't make changes that could be harmful based on a hunch"
There are many things that are simply uncertain and “untrue until proven otherwise” isn’t an exclusively optimal policy.
[1] https://lowninstitute.org/stents-dont-work-a-look-back-at-th...
What? This makes no sense. How do you explain anti-vaxxer parents with this perspective? Parents may feel they know best, but feeling and fact have nothing to do with each other.
Yeah, but I'll bet nothing happened as an outcome of this. No study, no communication to anyone else. That information probably just withered on the vine.
I did a molecular bio undergrad and had classes with a bunch of pre-med students. They had zero interest in the science, just getting A's. They did care about appearance and money, driving cool cars, and dating hot partners. I know my experience is purely anecdotal and not indicative of all doctors, but I came away from my undergrad experience highly unimpressed with our medical feedstock. The only students in upper level electives that cared were the research-track students.
I talk to my doctors regularly about medicinal chemistry and biochem -- they don't know anything. It's embrassing how little they retain or care.
He had a biological hypothesis that the scientific community disagreed with and tested it on himself for a case study to get data. That case study was successful and then became a clinical trial. That trial was replicated and shown to work. He then won a Nobel prize for that work and the risk he took. This is an evidence-based process. EBM doesn’t mean you disregard a N=1, it means you expand N=1 into N=10, then N=100,… before you apply something to the general population. This is loosely how phase-1,2,3,4 trials work in the US.
Dismissing EBM because of Marshall is like dismissing all of math because someone disproved a popular conjecture like the local-to-global conjecture. Sure the community sentiment had it wrong, but the systematic logical approach of Math got it right. In Marshall’s case the community sentiment had it wrong, but the EBM approach eventually got it right. Half this thread doesn’t even know what they are arguing against.
If you wouldn't mind reviewing https://news.ycombinator.com/newsguidelines.html and taking the intended spirit of the site more to heart, we'd be grateful.
If you wouldn't mind reviewing https://news.ycombinator.com/newsguidelines.html and taking the intended spirit of the site more to heart, we'd be grateful.
However, your "It's great that you're in medical school and very aware" is very patronizing and pointedly dismissive. Its a superficially polite acknowledgment that feels sarcastic rather than genuinely complimentary. I don't really mind, and I acknowledge the point you're trying to make. But if your goal is to curate a curious discussion and avoid snark you should model it too.
It's all too easy to fall into, and we do it too. In such cases it's good when people point it out, and I'm happy to take my own medicine.
The fix is to be more mindful of how easily this happens and edit one's comments to err on the side of unsnark. That's what I will do. If you're willing to do that as well, then HN will be better off in both cases.
(I do think it's great that you're in medical school and willing to share some of what you know on HN, but I shouldn't have singled out the "very aware" bit - that was me being passive-aggressive.)
Also medicine is an evidence-based practice because fundamentally our knowledge is woefully incomplete. Doctors are basically applied statisticians, the chemistry and biochemistry people are the researchers.
The oncologist could have written a paper (there are many single case papers), or started a trial by himself (requires a lot of organizing) if he was very intrigued. But of course one can’t do that for every above average case.
I have to say, in this particular case there is a very plausible mechanism and the trial would not be that hard. So it is a real shame that nothing was done with this.
This is the reason I started looking into the alternate dosing schedule.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9599830/
I'm comfortable calling that shameful. Not on any one in particular, it's a systemic problem that could be reduced with sufficient tenacity and courage to take risks.
You can only say that with hindsight because of the data over the past 30 years.
What if the data showed the opposite? Then the doctor would have given his patients a worse outcome all on a "hunch".
1. A single positive outcome with N=1 should generally not be the basis for making a medical recommendation.
2. It takes a mountain of research work to go from that to a study that you can draw meaningful conclusions from.
3. The hospital is not in the business of doing research, it's in the business of treating patients.
Regarding the first two: I think the anecdote being from 1995 suggests there would have been time to put together said mountain of research.
I’m not agreeing that this is shameful for the original doctor, but I do think it’s shameful if avenues for potential research are not taken because it’s inconvenient for the hospitals.
But cost is also important to patients. Or it would be in any universe that made sense.
Example: https://www.medicalnewstoday.com/articles/cancer-time-of-day...
They gave morning infusions because it was convenient. To get my father the evening infusion we had to hire private duty nurses to come to his apartment.
That they did it for one patient does not mean that they can do it for everyone - especially when it's not clear if it actually helped, due to a small sample size.
Nowhere do you start from 0 and go to 100. You take baby steps scaling up to see if the results hold.
This was Sloan-Kettering.
They gave morning infusions because it was convenient for them.
To get my father the evening infusion we had to hire private duty nurses to come to his apartment.
Since they clearly could alter the schedule, offering a limited number of later slots and comparing results would seem like the prudent response.
There's a difference between a doctor entertaining a medically-irrelevant suggestion from a patient (or patient's family), vs. assuming that the subsequent improvement was related to it, and then making that decision for some other patients (or suggesting it to them). The former is being accommodating, the latter is making treatment changes without good reason.
Improvement or no change aren't the only two possible outcomes for a patient. They could also get worse. What's worse, often neither improvement nor decline are obviously related to the treatment, or treatment changes.
Maybe it's the circadian rhythm thing. Maybe it's some delayed effects of something unrelated about the patient, that just coincided with your intervention. Maybe it's just a response to a change - any change. Or maybe it's just completely random. The point is, you don't know. You might feel like you do, or maybe it really looks obvious - but from N=1 you don't actually know, not enough to potentially bet other people's health on it.
Because maybe you do go ahead, and make a schedule change to another few patients - and few days later, suddenly and for no apparent reason, one of them goes into critical condition and dies soon after. Good luck convincing the grieving family, your colleagues, the board - and your own conscience - that the schedule change could not have possibly caused this. You won't, because you don't actually know.
They could already have made it worse with prior scheduling decisions, without having any idea.
Intentionally choosing to ignore a possibly harmful effect of the current lack of scheduling rules seems to me as blatantly unethical or worse as taking reasonable steps within what is already permitted to try to address a possible negative effect.
If concerned about making the schedule change for them: Provide the option. Add appropriate warnings if you like.
But also consider that any grieving families that finds out after the fact that there might be a known benefit to changing the scheduling would be equally hard to convince that you've not acted unethically and done harm.
In a sense, yes - but there's a difference between following established protocol or understanding, vs. changing it; the difference comes from operating under extreme uncertainty. It's a version of "if it ain't broken, don't fix it" - especially if you're not able to fully commit to identifying the problem, devising a fix, and verifying it's actually doing what you expect for reasons you expected.
> They could already have made it worse with prior scheduling decisions, without having any idea.
Or they could've made it better without having any idea. Point is, they had no idea either way.
> If concerned about making the schedule change for them: Provide the option. Add appropriate warnings if you like.
Even providing an option is already biasing the patient's decisions. Especially in matters of health, people will happily ignore all the warnings you can give (especially if they're mostly philosophical points about ethics or epistemology) and grasp for anything that could help. They're not going to be making a calm and objective choice. Doctors are fully aware of this, and with that awareness, presenting an option is really making a decision for yourself, but dumping any potential fallout on a patient. It's the 21st century, we know what informed choice is, and that wouldn't be it.
> But also consider that any grieving families that finds out after the fact that there might be a known benefit to changing the scheduling would be equally hard to convince that you've not acted unethically and done harm.
For better or worse, that's a big part of what evidence-based medicine is - a shield to protect you in situations like these. It lets you say that "might" wasn't enough - that the benefit wasn't actually "known", but merely anecdotally reported; that the benefit could be real, or could be coincidence, and there could be drawbacks too, unknown or under-reported (so the family didn't stumble on anecdotes of failure like did on anecdotes of success). It lets you say that there is an actual framework for evaluating what's ethical under uncertainty, and it deemed the risk too high. Most importantly, it lets you say all that, and have the entire medical community back you on this. Whether or not your conscience agrees, at the very least the will judge you as acting ethically and in best interest of the patient.
EBM and standard protocols are far from perfect - but they have solid ethical and epistemological grounding, and achieve the goal of minimizing harm to the extent possible under extreme uncertainty the medical field operates in.
2. Does it? Speaking directly out of my butt here (not in healthcare, not an academic), but the OP spoke of pretty acute symptoms specific to a treatment plan. If the treatment program is at all common, then a very straightforward A/B split of non-intervention / intervention.
Heck, even a questionnaire of past patients cross-referenced with historical records of appointment times could go a long way to validate the hypothesis.
3. This degree of specialization is for insects. If literal MDs in the field are too atomized to even surface research proposals, then that feels like an awful waste of edge-research capability.