Gene therapy — once heralded as a miracle cure for some genetic disorders — has had a chequered past, and recent developments do little to bestow confidence in this approach.

Although initially thought to be a success, a clinical trial that began in 1999 was temporarily halted when three out of eleven patients developed leukaemia following gene therapy to treat X-linked severe combined immunodeficiency (X-SCID). This unfortunate outcome led US-based scientists to re-evaluate this approach using mice to study its long-term effects. These scientists have now shown that treatment of immunodeficient mice by replacing the defective gene encoding the common cytokine receptor γ-chain (Il2rg) with the normal version, as was done in the human trial, caused lymphomas in a third of the animals in later life (Nature, 27 April 2006). Dr Niels-Bjarne Woods, one of the scientists who carried out the research, was “surprised by the strength of the association” (BBC News, 27 April 2006) and concluded that “preclinical experimental treatments involving transgenes should include long-term follow-up” (Nature, 27 April 2006).

Moreover, the development of cancer in the mice was not because insertion of the gene led to activation of the oncogene Lmo2, as was originally suggested to explain the complication in humans, but because IL-2Rγ itself has oncogenic properties. So, the development of leukaemia “may in fact have been an inevitable consequence of the treatment, not just a rare side effect” (New Scientist, 29 April 2006).

But Professor Adrian Thrasher, of Great Ormond Street Hospital, London, UK, who has successfully treated nine children using this approach and seen no cases of leukaemia, told the BBC that “The researchers have taken artificially high doses of these genes and given them to animals.” (BBC News, 27 April 2006).