Genophage

The genophage was a biological weapon deployed against the krogans by the turians during the Krogan Rebellions, when the krogan population was reaching saturation point. It was designed to reduce krogan numbers to crippling levels by 'infecting' them with a genetic mutation. Every single krogan is infected. The genophage does not affect fertility but makes only one in one thousand births viable. Because of this the krogan are a dying race, soon to be extinct.

The genophage was originally developed by the salarians. They believed that, as the consequences would be so devastating, no one would ever actually deploy the genophage and it was intended to be a deterrent. However, the salarians and the turians have different military strategies, and the turians only understand a concept of 'total war'. Once the genophage was complete, the turians used it, and krogan numbers began to dwindle rapidly. Any female krogan who could carry young to term became a prize of war who was viciously fought over. A female warlord named Shiagur actually used her fertility as a bargaining chip to attract the strongest males to her army.

After several hundred years of living with the genophage, the knowledge their species will soon be extinct has created a kind of fatalism amongst the krogan that makes them dangerous opponents - they don't care who they attack or kill, or what risks they take, because they'll all be dead soon anyway. A few individuals like Wrex have tried to rebuild the species, or at least curtail their decline by focusing on breeding, but the natural territorial instincts of the krogan usually work against their efforts.

There is no cure for the genophage, though some krogan groups have invested in companies like Binary Helix to try and research one. There are virtually no krogan scientists, and nobody else is rushing to return the krogan to their former numbers. This has led to some krogan trying bizarre alternatives. As Garrus Vakarian tells an incredulous Commander Shepard, there is a healthy trade in krogan testicles on the black market because of the unsubstantiated belief that testicle transplants can improve their fertility.

Somehow, possibly with the assistance of Binary Helix or even Sovereign, Saren Arterius managed to develop a genophage cure and used it to breed a krogan army on Virmire. Shepard's inexplicable determination to destroy the cure instead of reclaiming it for the krogan caused a rift between Commander Shepard and Wrex. The exact nature of the cure was never discovered and it was destroyed when Shepard and Captain Kirrahe blew up the facility. What allowed the genophage cure to be is unknown, and the source has yet to be discovered.