Pioneer Vector Integration and Tumorigenesis

W ith some early molecular work in oncology and virology in Harald zur Hausen’s lab in Heidelberg, Germany, a background in internal medicine and oncology (courtesy of learning to treat Hodgkin’s disease from Volker Diehl, Cologne, Germany), I had developed a fascination with stem cell transplantation as a way to treat otherwise intractable diseases in humans. So I jumped at the opportunity to work on a gene therapy project in Rainer Storb’s division at the Hutch in Seattle, together with Hans-Peter Kiem and the late Friedrich Schuening. Gene therapy was all the rage of the day; many people convinced—or trying to convince others—that gene transfer would solve many of the major medical problems of humankind. My own view, under the influence of Rainer’s sharp scientific wit and guidance, was that perhaps the stably integrating retrovirus vectors, biologically inert as we thought they were, could at least help decipher the structure of human hematopoiesis. At the very least, they could help to understand its regeneration after hematopoietic stem cell transplantation— that meant as soon as we would succeed making them enter human blood-forming stem cells in significant numbers.

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