A projectile must retain enough kinetic energy to continue moving for a long time, even in a medium, no matter how strong it is. This is achieved primarily through the speed and mass of the projectile. The caliber of a projectile does not play the primary role; the length and diameter are determined by the weight of the projectile and also by internal ballistic parameters. How high the impact velocity is and how much more a projectile must be very strong designed. Anti tank ammo is a good example.
For shooting game according this concepts, at some point only solid bullets will be considered. Deformation or fragmentation of a bullet no longer play a role, on the contrary, can have a negative impact. What kills is the great temporary cavitation that results by the use of such high velocity bullets, but a cavitation which has to occur on the right place, meaning after a good shot placement. There is primary no schock, otherwise the initial belief that it is enough to hit a game somewhere to incapacitate it would be true, which is not the case. The discussion about the working of the 257 Weatherby Magnum cartridge illustrates some of this.
The Weatherby concept was therefore not bad in theory and for this reason the cartridge 378 Weatherby Magnum was rightly considered the maximum needed to kill the heaviest animals. Theoretically, that may be true, but in practice, for a lot of reasons, things turned out differently. You cannot mix highly modern ballistic concepts with old traditional hunting and shooting concepts. This is also the case when talking about the old cartridge 600 Nitro Express.