The term "cytokine storm" appears to have been first used in 1993 in a discussion of graft vs. host disease; CRS as an adverse effect has been known since the approval of the first monoclonal antibody drug, muromonab-CD3, which causes CRS, but people working in the field of drug development at biotech and pharmaceutical companies, regulatory agencies, and academia began to more intensely discuss methods to classify it and how to mitigate its risk following the disastrous 2006 Phase I clinical trial of TGN 1412, in which the six subjects experienced severe CRS.