http://www.youtube.com/watch?v=Tja6_h4lT6AThe title references an idea first conceived by Drunvalo Melchizedek concerning the possibility of reaching a state of evolution at which the body would have two more than the normal 46 total chromosomes and leave a currently disharmonious state.<2><3> The premise is that humans would deviate from the current state of human DNA which contains 44 autosomes and 2 sex chromosomes. The next step of evolution would likely have 46 and 2 chromosomes in their DNA, according to Melchizedek.
Given Tool's developed sense of humour, it should perhaps be noted that chimpanzees have 46 autosomes and 2 sex chromosomes. From that perspective, it could be argued that the song is perhaps parodying the prediction of Melchizedek or at the very least very sarcastically musing about the choices that humans tend to collectively make.
Furthermore, the song references a wish to experience change through the "shadow"; an idea which represents the parts of one's personality that one hates and fears, which also exists as a recurring theme in the work of Carl Jung.<4>
http://en.wikipedia.org/wiki/Forty-Six_&_2Just thought I add this for fun.