Sentries and Saboteurs; October 1993; Scientific American Magazine; by W. Wayt Gibbs; 5 Page(s)

Doctors treating cancer with chemotherapy play the odds. Too little drug and the diseased tissue will survive; too much and the damage to healthy cells will be more than the patient can bear. But some researchers believe gene therapy can increase the spread. In upcoming clinical trials they intend to insert into cancer patients' DNA mutations that either make healthy cells more tolerant of existing medication or make tumors more vulnerable to it. "This is a totally novel approach, but a natural extension of gene therapy," says Albert B. Deisseroth of the University of Texas M.D. Anderson Cancer Center in Houston.

In June the Recombinant DNA Advisory Committee of the National Institutes of Health approved two protocols for human tests of a strategy that Deisseroth calls "chemoprotection." He and others plan to genetically modify patients' bone marrow cells so they can withstand more courses and higher doses of chemotherapy. Human trials are also under way to test another gene therapy technique that is essentially a mirror image of chemoprotection. Rather than inserting "sentries" to guard healthy cells against dangerous drugs, a strategy called molecular surgery sends in genetic "saboteurs" to make tumor cells susceptible to a normally harmless medicine.