杏吧原创

MICE struck down by leukaemia have become the first animals to die from cancer as a direct result of faulty gene therapy.

Gene therapy pioneers have always worried that the viruses they use to shuttle therapeutic genes into patients might accidentally dump their cargo in the wrong spot on chromosomes. If this happened, the inserted DNA could in very rare cases trigger the expression of cancer-causing 鈥渙ncogenes鈥�, or disrupt sentinel genes that guard against cancer.

It seems that these fears were justified. While investigating potential problems of gene therapy, such as failure of the transplanted cells to develop properly, a team of scientists in Germany gave 10 mice bone marrow cells that had been altered by gene therapy. To their surprise, all the mice developed leukaemia to varying degrees.

It turned out that the retrovirus 鈥渧ector鈥� used to load a gene into the bone marrow cells had inadvertently dumped its cargo smack-bang into a known oncogene. 鈥淚t鈥檚 the first time such a vector has produced disease,鈥� says Christopher Baum of the Hannover Medical School, head of the team that made the discovery.

The disrupted gene, called Evi1, makes a genetic 鈥渟witch鈥� vital for development of various organs, including kidneys. But it鈥檚 not meant to be switched on in bone marrow cells, many of which mature into blood cells. Activating this gene is known to aggravate leukaemia in mice and people.

Baum stresses, however, that the risks are small. 鈥淗undreds of thousands of animals have been treated without such effects,鈥� he says. 鈥淚t鈥檚 bad luck we hit the wrong place.鈥� The chance of this happening had previously been estimated at about 1 in 10 million, he says.

Norman Nevin, chairman of the British government鈥檚 Gene Therapy Advisory Committee (GTAC), agrees. 鈥淚 personally feel that overall, there shouldn鈥檛 be concern because the risk is small,鈥� he says. 鈥淏ut it highlights the importance of having a system of follow-up for patients who鈥檝e had gene therapy.鈥� Britain became the first country to set up such a system a year ago. Managed by GTAC鈥檚 secretariat, it routinely monitors all patients and even their children up to the age of 16.

In Britain, around 400 patients have received gene therapy, though only a handful were treated with retroviruses. They include two 鈥渂ubble babies鈥� who would otherwise be condemned to life in a germ-free environment because their immune systems didn鈥檛 work. One, Rhys Evans, has already effectively been cured through gene therapy at Great Ormond Street Hospital (New 杏吧原创, 6 April, p 7), and another is improving, according to team head Adrian Thrasher.

Thrasher himself sees no need to panic. 鈥淚 agree there鈥檚 a finite risk of generating leukaemia using this technology, though the risks are very small,鈥� he says. 鈥淏ut systematic risk assessment is essential, as it is for any new therapy.鈥�