The synthesis works because all three examples turn on the same hinge, even though you let the reader find it: suppression only holds when whatever escapes it pays a cost.
Elk pay in vigilance and lost foraging, resistant pests pay the enzymatic tax you describe, resistant tumor cells pay a metabolic one. That's the load-bearing assumption under adaptive therapy, and it's exactly why your caution about generalizing it is right. Where a resistant clone is close to cost-free, the sensitive cells can't hold it back, and the ecology stops rescuing you.
Very interesting article! People have been doing this for a very long time for cystic fibrosis chronic infections: cycling one month on one month off inhaled antibiotics, or alternating antibiotics with different mechanisms (e.g. aminoglycoside and beta lactam) since eradicating chronic infections is really hard and the theory is the month off maintains susceptibility for the reasons you talk about here. I’ve always wondered why cancer treatment doesn’t do this kind of thing more, glad to see it’s starting to happen!
Evolution in action. That was the tag line for BEACON, a $25M consortium of 5 universities looking for ways to apply evolutionary dynamics more broadly. They funded my first podcast, called VSI: Variation Selection Inheritance.
Another paradigm-altering idea came from Bob Ader at the University of Rochester where I was in a PhD program inside a medical school. From February 2017, "The Placebo Files."
“his goal is that you find it ‘worth reading’ rather than necessarily ‘being right.’”
This doesn’t seem like a very admirable goal?
Interesting comparisons with chemo dosing.
Another comparison is the approach to treatment-resistant malaria, which is to use regimens of multiple medications at once to make it harder for the parasite to develop resistance (this is mandated by WHO I believe). So another solution would be use even more pesticides, as combinations.
If the IPM moderate/timely pesticide approach works better on a reasonable time scale, why is it not universally adopted? I would think every money-hungry big Ag farm would be doing this. Is it a tragedy of the commons situation?
In a single, broad stroke, the entire intellectual history of humanity is people responding to each other saying, 'that is a valid argument (i.e. "worth reading") but it is unsound (i.e. not "necessarily right") for whatever reason(s).'
It's merely a fun/self-deprecating way of saying, 'we are entering the intellectual arena but do not think that I am infallible. Think about the piece, engage with it, and decide for yourself.'
It depends how you measure IPM practices, but it's estimated that ~95% of American farms practice some form of it, with ~20% using "intensive" IPM.
The synthesis works because all three examples turn on the same hinge, even though you let the reader find it: suppression only holds when whatever escapes it pays a cost.
Elk pay in vigilance and lost foraging, resistant pests pay the enzymatic tax you describe, resistant tumor cells pay a metabolic one. That's the load-bearing assumption under adaptive therapy, and it's exactly why your caution about generalizing it is right. Where a resistant clone is close to cost-free, the sensitive cells can't hold it back, and the ecology stops rescuing you.
The cost is the whole game !
Great article, thank you.
Very interesting article! People have been doing this for a very long time for cystic fibrosis chronic infections: cycling one month on one month off inhaled antibiotics, or alternating antibiotics with different mechanisms (e.g. aminoglycoside and beta lactam) since eradicating chronic infections is really hard and the theory is the month off maintains susceptibility for the reasons you talk about here. I’ve always wondered why cancer treatment doesn’t do this kind of thing more, glad to see it’s starting to happen!
Evolution in action. That was the tag line for BEACON, a $25M consortium of 5 universities looking for ways to apply evolutionary dynamics more broadly. They funded my first podcast, called VSI: Variation Selection Inheritance.
https://randallhayes.substack.com/podcast
Another paradigm-altering idea came from Bob Ader at the University of Rochester where I was in a PhD program inside a medical school. From February 2017, "The Placebo Files."
http://www.intergalacticmedicineshow.com/cgi-bin/mag.cgi?do=columns&vol=randall_hayes&article=014
“his goal is that you find it ‘worth reading’ rather than necessarily ‘being right.’”
This doesn’t seem like a very admirable goal?
Interesting comparisons with chemo dosing.
Another comparison is the approach to treatment-resistant malaria, which is to use regimens of multiple medications at once to make it harder for the parasite to develop resistance (this is mandated by WHO I believe). So another solution would be use even more pesticides, as combinations.
If the IPM moderate/timely pesticide approach works better on a reasonable time scale, why is it not universally adopted? I would think every money-hungry big Ag farm would be doing this. Is it a tragedy of the commons situation?
In a single, broad stroke, the entire intellectual history of humanity is people responding to each other saying, 'that is a valid argument (i.e. "worth reading") but it is unsound (i.e. not "necessarily right") for whatever reason(s).'
It's merely a fun/self-deprecating way of saying, 'we are entering the intellectual arena but do not think that I am infallible. Think about the piece, engage with it, and decide for yourself.'
It depends how you measure IPM practices, but it's estimated that ~95% of American farms practice some form of it, with ~20% using "intensive" IPM.