Though modern methods for introducing transgenes into an organism are diverse, there are two historically important procedures that were the progenitors of transgenic organisms. Palmiter and Brinster were the first to introduce foreign genetic material to an organism. They added the gene for human growth hormone (HGH) to a mouse zygote at the point where the haploid genomes are fusing to cause random incorporation of the transgene into the host genome. In addition to the transgene payload, Palmiter and Brinster added a promoter in front of the transgene in order to get expression in the transformed mice. Following this historical achievement came the knock-in engineering in embryonic stem (ES) cells developed by Capecchi, Martin, and Smithies. This method involved in vitro transformation of ES cells as opposed to direct zygotic injection. They removed the promoter from the transgene, added arms of homology and a neomycin resistance gene. The promoter is unnecessary as the arms of homology will target the transgene to an already active promoter in a pre-existing gene. The transgenes are then added to electroporated ES cells in order to allow the transgene payload to enter the ES cells. The cells that take up the transgene and undergo a double-stranded (DS) break that matches the transgene’s arms of homology get transformed. Then, the antibiotic neomycin is added to the cultured cells to select for the cells that were transformed. These transformed cells are injected into a mouse blastocyst in order to express the transgene in the adult organism.