When Coulson stepped down as the director of S.H.I.E.L.D., he asked the President that the next director should be a powered person and the President order Talbot to find such a person. However, Talbot was unable to find a powered person with the skills necessary to become director of S.H.I.E.L.D. thus Talbot had the idea to, instead of finding someone who already had powers, give powers to a person already qualified to become director.
Whenever Mace needed to use his super-strength, his assistant Burrows would inject with a special drug that'd give him temporary super-strength.
The drug that Mace takes is a modified version of the drug Mr. Hyde took which gave him his super-strength. However, according to Talbot they "took out all the bad stuff" before giving it to Mace. Furthermore, this new drug is specially calibrated for Mace's DNA so it's unknown if it'd work on anyone else.
In order to maintain the farce, the truth about Mace's powers was kept secret, even from Coulson and the team.
In "BOOM," Simmons warns Mace that after analyzing the drug that give him his super-strength, she's learned that the drug is potentially lethal and even taking one more dose could kill him.