

After testing the living Sea Emperor Leviathan, the Architects discover she is too old to produce Enzyme 42 potent enough to work as a permanent cure.The Architects place various relics from other alien races, including humankind, in the Primary Containment Facility.It is believed the Architects also discovered the Ancient Skeleton and constructed the Lost River Laboratory Cache around this time. They capture a 1600-year-old Sea Emperor Leviathan and her seven eggs and place them in the Primary Containment Facility. They construct the Primary Containment Facility and Alien Arch Caches. The Architects discover the Sea Emperor Leviathan species produces Enzyme 42, a compound that provides immunity to Kharaa.The resulting crater blocks the entrance to the Architect cache and the impact toppled one of the cache's pillars. A meteorite strikes 4546B in the Dunes biome.

It is believed the Architects also discovered the Gargantuan Fossil around this time and began to take samples from its rib cage. The Architects construct the Quarantine Enforcement Platform, Disease Research Facility, Alien Thermal Plant, and Sanctuary Caches and begin constructing Warpers (whether this was the first time Warpers were constructed is unknown).

The Architects quarantined their core worlds and brought Kharaa to isolated disease research facilities, including on Planet 4546B, in order to research and develop a cure. A network error caused the Architects' routine quarantine procedure to fail, resulting in at least 143 billion deaths on their core worlds.
