The FHAT transgenic mice genetically engineered with a “humanized humoral immune” system can be of better valuable in therapeutic antibody development, since the derivative antibodies are preselected in vivo. In contrast, antibodies derived from non-animal sources have very artificial antibody sequences that do not exist in nature. These non-nature-selected antibody sequences may perform well in vitro but will behave completely different in vivo. One of the common problems is that the artificial antibodies will disappear in vivo without disclosing their whereabouts. This could due to the fact that the antibodies bind to unknown epitopes. Alternatively, the antibodies are captured by cells or simply degraded or sliced in vivo. Antibodies derived from live animals have passed nature-selection and usually do not have such issues.