with iron and steel, as long as you have adequate margin between the max stresses and plastic deformation, the fatigue life is nearly infinite
This is not entirely true, there are also iron/steel alloys around that will bite you if you try to prevent fatigue by static margin. Anway this philosophy will lead to structural weight inacceptable for an airframe. An airframe that heavy will have an infinite life because it will not be economic to operate and hence be parked all the time. Except for the military, where cost has not been an issue for some decades.
A Comet 1 with round windows would have had a longer life, but would eventually have failed catastrophically as well. As other airframes did. You can never reliably prevent a crack from happening, whether due to stress concentration, manufacturing flaw, accidental damage or whatever. The trick is to design the airframe in a way that you can allow cracks until you eventually detect and repair them. You need to prevent uncontrolled, instable crack growth. Which can be accomplished by adequate design without the weight penalty of low stress levels. A lesson that took a dozen hull losses and half a century to learn.