Man-made, rewiring of a pre-disposition, playing God
Certain groups started a psychological movement known as conversion therapy for homosexuals which mostly involved somewhat unethical and extreme tactics. Macklemore is referencing the previous phrase and expressing his opinion that homosexuality is controlled by biology and trying to change this would be like trying to be God.
There is also irony in the fact that these same people who would otherwise condemn “playing God” to be a sin are doing just that.
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