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.
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.
> 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.
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.
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.
Theryq - why would they go with this name when everyone in the field knows about the Therac-25 radiation overexposure incidents?
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.
> 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.
Redemption arc.
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.
> 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.
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.
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:
https://www.nature.com/articles/s41571-022-00697-z
Interesting the effect's reason is still unclear.
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.
Sounds a little too close, in both name and concept, to Therac for my comfort.
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.