If there are three phases to scientific discovery—gee whiz, aw shucks, and yes, but—then we are well into the yes, but phase of gene therapy.

Gee whiz
DNA, the stuff of genes, the fundamental unit of life, can be isolated, sequenced, rearranged, and domesticated. And some human diseases can be directly attributed to specific pieces of DNA, the exact location and structure of which is known. Grandly elegant science and mindboggling bravado have explained a lot of fundamental pathobiology and such discoveries continue at an ever increasing pace. Promises of cures were made, industrial-academic partnerships flourished, books were written (six books aimed at the general public on gene therapy rest on my bookshelf). A new millennium seemed at hand when diseases like cystic fibrosis could be cured once and for all by gene therapy.

Aw shucks
In science as in the rest of life, things that look too good to be true often are. Alas, the difficulties in inserting the right gene in the right place in sufficient amounts without unreasonable risk were greatly underestimated. Major efforts to do it were launched, but at some point it became undeniably clear that the rumors of a dawn of a new therapeutic millennium were gross exaggerations.

Yes, but
Cystic fibrosis is not cured, but we have learned a lot in the effort. Yes, it is possible to deliver DNA to the lungs, but better and safer delivery systems are needed to make gene therapy a reality. And they are being developed.

This volume is authored by multiple experts in relevant fields and is organized according to this sequence of scientific discovery—Part One is gee whiz, Part Two is aw shucks, and Part Three is yes, but. In an epilogue, an FDA official discusses some practical issues, regulatory matters that will have to be dealt with to make gene therapy a real tool for the clinician.