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The Glimmering Promise of Gene Therapy

  • Wednesday, November 1, 2006
  • By Horace Freeland Judson

Its history is marred by failures, false hopes, and even death, but for a number of the most horrendous human diseases, gene therapy still holds the promise of a cure. Now, for the first time, there is reason to believe that it is actually working.

   

By the late 1960s, molecular biologists had erected an overarching explanation of how genes work--their substance, their structure, their replication, their expression, their regulation or control. Or at least they had done so in outline, for prokaryotes, the simplest single-celled organisms (which include bacteria), and for the viruses, called bacteriophages, that prey upon them. The leaders of the field were now looking to a far more difficult problem: doing it all over again for higher organisms.

What this new generation of molecular biology demanded, and what was developed in just a few years, was a set of methods for investigating and precisely manipulating the genetics of eukaryotes, including animals and plants. With reverse transcriptase, which was discovered independently by ­Howard Temin and David Baltimore in 1970, genes encoded in RNA could be read back into DNA. With Daniel Nathans's and Hamilton Smith's work on restriction enzymes, segments of DNA could be snipped out at chosen sites. In a rush, from laboratories chiefly at Stanford University, came ways to link together genetic material from disparate sources. "We will be able to combine anything with anything," one senior scientist told me at the time. "We can combine duck with orange." The initial purpose was to get at the most basic questions of cellular biology, to find out exactly what individual genes do and how they do it. Immediately, though, a shining hope dawned: that this toolbox could be carried from the laboratory to the clinic, to cure hereditary diseases caused by genetic defects. Already, some scientists were dreaming of gene therapy.

 

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