For Purely Scientific Purposes

First things first, head back into MacDougall's office to grab the mission. Once you're outside, hop on your horse. As you ride off, you'll be chatting with your companions. While you're listening, make sure to switch to your highest-powered rifle before you get too far.

You won't have to ride for too long before you run into a pretty big bear that decides it wants to attack. The best way to handle this is to activate your Dead Eye right as it lunges at you. If you time it right, you can land a shot straight to its skull and take it down in one go. Trust me, this is way easier than trying to unload a bunch of bullets into it.

Keep following the path until you and MacDougall dismount your horses and walk up to a cabin. After a cutscene plays out, you'll find yourself in a shootout with a bunch of Native Americans. You'll already be in cover, so use it to your advantage. Aim for the heads of the enemies as they pop out from cover, and use your best rifle for maximum effect.

Once you've dealt with all the attackers, get back on your horse and head towards Blackwater with MacDougall. Keep your wits about you, because you'll be ambushed twice on the way back. Have that high-powered rifle ready to go and take them all down quickly before they can get the drop on either of you.

Finally, you'll arrive in an alley. Dismount your horse and follow MacDougall to trigger another cutscene, which will mark the end of the mission.