Having hunted more than a few buffalo, I have to say that, in today's world of once in a lifetime opportunitites, where people pay to hunt, or there exists a tangible penalty for animals wounded and lost, a .50 cal. ML is marginal at the VERY best for the task at hand. In the 19th century, if a Buffalo Runner drew blood but couldn't recover the animal, there wasn't someone demanding payment, stamping their tag, or declaring that the hunt they had paid for was over. 19th century hunters had the dubious luxury of underestimating their quarry, we don't.
I took my first free roaming bull at under 20 yards with a .416 Rem and the bull took two rounds into the heart/lungs and didn't even flinch. Both were perfect shots. The third quick shot hit him in the spine and he dropped. Amazingly, NONE of those 400 grain bullets at 2400 fps exited the only moderately sized yet very old Yukon bull. Had the third shot not hit his spine and had he determined our position, he could have stomped us had he so desired, NO DOUBT. On another hunt, I had a 405 grain Remington core-lokt from a 45-70 literally SPLIT IN HALF by a sharp edge of broadside bison skull and fail to penetrate to the brain. The bull fell and appeared dead but got up and ran like hell when we got to within 10 feet of him! Again, he could have stomped us had he so desired but he (fortunately) ran in the other direction and a second bullet from my 1885 hit him in the spine ending it. My next attempt at a neck shot in Custer State Park saw me using the .416 loaded with solids with very good results.
Frankly, Bison will die with a .50 round ball in a lung but they will not do so quickly and on a big bodied bull I certainly have doubts as to the penetration capability of a .50 cal. You may get both lungs but maybe not. Conicals may more reliably take both lungs and lead to a quicker death but I still like bigger holes yielding more blood if I am paying big bucks for a hunt.
Honestly, when it comes to free roaming bison in a world where people are paying good money for hunts or drawing once in a lifetime tags, I think reasonable BP bison calibres start at 12 bore. This was Samuel White Baker's minimum on Cape Buffalo and they are LESS massive (particularly around the vitals) than NA bison by a pretty fair amount. My next hunt will see me using my 8 bore.
Also, for those interested, there is an article I wrote in the latest issue of Fair Chase magazine about free roaming bison opportunities....you don't need to hunt 'em behind a fence.
JMHO,
Buffler Runner