Another interesting part of the story is the user element. The issue was most often triggered by fast, experienced technicians who were able to key commands more quickly than Therac engineers anticipated:
> After strenuous work, the physicist and operator were able to reproduce the error 54 message. They determined that speed in editing the data entry was a key factor in producing error 54.
Some years later, I interviewed at Knight Capital, just a couple of weeks before their blowup. (Dreadful interview at which I did dreadfully, being asked to write C _over the phone_ by a supremely uninterested engineer. Quite a red flag in retrospect.)
> Therac-25 is a great case study for software engineers too, recommend reading the Wikipedia article for anyone who hasn't, it's not too long.
I re-read the original paper every few months, more frequently if I'm working on Safety-of-Life-Critical equipment. Which, given my day job, means I'm re-reading it every couple of weeks at most.
The audience of this website is disproportionately aware of the Therac-25 compared to the general public. For the obvious reason, engineering, but also geographically: The Therac-25 being a North American incident that affected Canada and the US. Whereas Theryc is a French company.
While I do agree with your point, as a Swede not even born when the incidents happen I still knew about it, was brought up in a computer science class.
Exactly what I thought as soon as I learned the name.
It's like, man, how to kill a product?
No pun intended.
It could even work? But you put yourself behind such a poorly placed 8 ball when you do these things. Even among researchers, people are a little superstitious about stuff like this. It's always in the back of everyone's mind.
> Even among researchers, people are a little superstitious about stuff like this.
Being superstitious is not common in the medical treatment world, where weird product names are common.
A doctor isn’t going to include the device’s brand name in their decision process for treating a cancer patient.
The Therac-25 case study is noted in the medical world but not to the same extent as in engineering. The case was a tragedy of bad engineering, but the doctors involved in directing the treatments were not at fault for the radiation over exposures.
I doubt any of that is valid. Therac-25 happened 44 years ago, that's a very long time, and many people involved in cancer research today weren't even alive when it happened.
"Theryq" and "Therac" are not quite the same either. The word "therapy" and derivatives of it using "thera" are still used widely across the medical industry.
So I'm not really sure why anyone here is making a big deal about the name of the company being "Theryq".
> Currently, the most plausible theory emerging from her team’s research points to metabolism: Healthy and cancerous cells may process reactive oxygen species—unstable oxygen-containing molecules generated during radiation—in very different ways.
There was also a study that showed that chemotherapy efficacy was enhanced by fasting before treatment.
It seems that when calories are scarce, healthy cells turtle up while cancer cells keep consuming, so fasting reduces absorption rates in healthy tissues and thus collateral damage.
Healthy cells CAN turtle-up, whereas cancer cells engage in unregulated reproduction. Also, some cancer cells can only consume glucose. Which, in a fasted state, would mean that the majority of energy would be in ketones(if the individual were metabolically healthy), starving the cancer cells to death.
Because the cancers cells adapt! (fast reproduction and high mutation rate of the cancerous cells make that process quicker than antibiotics resistance)
The major issue isn't the speed of delivery, and the cancer.
The key question is how do you spare normal tissue, and how do you prove the normal tissue is spared in the long term. Current answer is: You break it apart into multiple sessions, the anti-thesis of FLASH.
from the article (pay attention to the part in italics):
FLASH radiotherapy flips the conventional approach on its head, delivering a single dose of ultrahigh-power radiation in a burst that typically lasts less than one-tenth of a second. In study after study, this technique causes significantly less injury to normal tissue than conventional radiation does, without compromising its antitumor effect.
Hey, FLASH finally hit Hacker News! I remember my professors talking about this in graduate school. It's a fairly well-established effect: the tumor selectivity of radiation is much better at ultra-high dose rates. It is still unclear exactly why. But there are a lot of studies about it:
I was starting to infer there was a better focusing ability so it could start and exit as a broad cone of radiation and keep the peak intensity at the tip of the focal cones at the tumor-tissue, and the short pulse also helped the healthy tissue.
But the way this sounds, it's more like a straight beam delivering similar intensity to healthy and tumor tissue but the biological effect strongly differs between healthy vs tumor tissue?
Yes, the radiation dose under the conventional metric (energy divided by mass) is the same, but the effects on biological systems change. I included a little speculation on the chemistry in my response to a sibling comment.
My guess would be that the radiation doesn't itself care but that tumors have some other characteristic (like multiplying rapidly) that makes them more susceptible to it. Similarly to how you can sometimes attack them with medication that inhibits cell division.
Yeah that's the conventional dose rate effect, not the FLASH effect. The FLASH effect happens on timescales so short that ordinary considerations like the cell cycle or DNA repair mechanisms are inherently ruled out. Instead it might have to do with the type of radical species that form in normal cells versus tumors, possibly related to oxygenation, pH, glycolysis byproducts, etc.
The first interaction of radiation with tissue is usually this:
H2O + ħv >> H2O+ + e- (fugitive)
The radical ion H2O+ is extremely reactive and usually protonates another water molecule immediately:
H2O+ + H2O >> H3O+ + OH*
The hydroxyl radical has a half life of about a nanosecond and will usually be the main "reagent", diffusing until it runs into an organic molecule which will be oxidized and thus degraded. At high enough dose rates, the peak concentration of hydroxyl radicals and more stable radicals like superoxide could be much higher, leading to "nonlinear" effects, i.e. byproducts of multiple radicals interacting with each other or a protein.
The sidebar mentions heavier particles having a pronounced Bragg Peak[0] and also existing approaches like multi-beam targeting. The FLASH effect in the article is yet another tool to limit the surrounding damage.
I recall someone was analyzing the refractive index of various tissues in order to tighten the target area for multi beam radiation therapy. Particularly for brain cancers. By hitting from multiple angles the dosage in surrounding tissues is lower, and by calculating how the head lenses the beam you reduce the high dose area in the middle, like a 3d Venn diagram.
But I don’t remember is whether that experiment became SOP or not.
Seems not in this case. But I believe the use case was deep brain tumors, like the hippocampus, where any beam alignment problems could be life altering.
I generally don't trust cancer-communication if it's juiced up like this incredible headline. There has been huge amounts of progress. We don't need silicon valley idiots starting to make proclamations. It's doing fine without your mediocrity.
> Previous models had hardware interlocks to prevent such faults, but the Therac-25 had removed them, depending instead on software checks for safety.
https://en.wikipedia.org/wiki/Therac-25
Another interesting part of the story is the user element. The issue was most often triggered by fast, experienced technicians who were able to key commands more quickly than Therac engineers anticipated:
> After strenuous work, the physicist and operator were able to reproduce the error 54 message. They determined that speed in editing the data entry was a key factor in producing error 54.
Some years later, I interviewed at Knight Capital, just a couple of weeks before their blowup. (Dreadful interview at which I did dreadfully, being asked to write C _over the phone_ by a supremely uninterested engineer. Quite a red flag in retrospect.)
I re-read the original paper every few months, more frequently if I'm working on Safety-of-Life-Critical equipment. Which, given my day job, means I'm re-reading it every couple of weeks at most.
Keeps you sharp, doesn't it?
CGR who provided the accelerators and basic PDP11-based computing platform were a French company.
> Whereas Theryc is a French company.
I have been a Citroën enthusiast for about 30 years. I love French cars.
I have repaired lots of Valeo electronics modules for vehicles.
I'm not sticking my head in a French fucking particle accelerator.
It's like, man, how to kill a product?
No pun intended.
It could even work? But you put yourself behind such a poorly placed 8 ball when you do these things. Even among researchers, people are a little superstitious about stuff like this. It's always in the back of everyone's mind.
Being superstitious is not common in the medical treatment world, where weird product names are common.
A doctor isn’t going to include the device’s brand name in their decision process for treating a cancer patient.
The Therac-25 case study is noted in the medical world but not to the same extent as in engineering. The case was a tragedy of bad engineering, but the doctors involved in directing the treatments were not at fault for the radiation over exposures.
"Theryq" and "Therac" are not quite the same either. The word "therapy" and derivatives of it using "thera" are still used widely across the medical industry.
So I'm not really sure why anyone here is making a big deal about the name of the company being "Theryq".
"This name makes me uncomfortable. I think I'd rather die of cancer."
Reminds me of this which I (think) was linked here a while ago: https://www.nature.com/articles/s12276-020-0384-2
It really does feel like all these piecemeal cancer treatments are converging on something resembling a cure.
It seems that when calories are scarce, healthy cells turtle up while cancer cells keep consuming, so fasting reduces absorption rates in healthy tissues and thus collateral damage.
The key question is how do you spare normal tissue, and how do you prove the normal tissue is spared in the long term. Current answer is: You break it apart into multiple sessions, the anti-thesis of FLASH.
Source: my wife is a radiation oncologist.
FLASH radiotherapy flips the conventional approach on its head, delivering a single dose of ultrahigh-power radiation in a burst that typically lasts less than one-tenth of a second. In study after study, this technique causes significantly less injury to normal tissue than conventional radiation does, without compromising its antitumor effect.
https://www.nature.com/articles/s41571-022-00697-z
It'll be nice when we figure it out, then we can understand the unintended consequences better.
Not that it should prevent its use or anything; fuck cancer.
I was starting to infer there was a better focusing ability so it could start and exit as a broad cone of radiation and keep the peak intensity at the tip of the focal cones at the tumor-tissue, and the short pulse also helped the healthy tissue.
But the way this sounds, it's more like a straight beam delivering similar intensity to healthy and tumor tissue but the biological effect strongly differs between healthy vs tumor tissue?
The first interaction of radiation with tissue is usually this:
H2O + ħv >> H2O+ + e- (fugitive)
The radical ion H2O+ is extremely reactive and usually protonates another water molecule immediately:
H2O+ + H2O >> H3O+ + OH*
The hydroxyl radical has a half life of about a nanosecond and will usually be the main "reagent", diffusing until it runs into an organic molecule which will be oxidized and thus degraded. At high enough dose rates, the peak concentration of hydroxyl radicals and more stable radicals like superoxide could be much higher, leading to "nonlinear" effects, i.e. byproducts of multiple radicals interacting with each other or a protein.
[0] https://en.wikipedia.org/wiki/Bragg_peak
But I don’t remember is whether that experiment became SOP or not.
However that’s the current theory, of a long line of theories that did not pan out.
Those aren’t superstition, just common sense.