I too have been a long investor for some time. As I see it ISIS, like most biotech companies are run by management that seems to focus more on the science and less on the PR hype that tend to drive the stock. It is my belief that ISIS has the science, the technology but since ISIS is not a household name (yet), like J & J, Amgen, or Genentech, for that matter .... there is no impetus presently to move the stock .... I feel this is about to change, with drugs in late clinicals and TIGER ....... this best kept secret (ISIS) will go from a whisper to a shout very quickly ...... I'm buying more on the dips, good investing to all long ISIS shareholders.