BACTERIA genetically modified to make a drug have been given to people for the first time. The bacteria are designed to treat inflammatory bowel disease by producing a human immune protein that dampens inflammation.
GM bacteria are widely used to make food and drugs. But the prospect of drug-producing gut bugs getting into the wrong people or swapping genes with other bacteria is of particular concern (New 杏吧原创, 15 June 2002, p 26). To address such fears, the bugs have been altered so that although they can thrive in the human gut, they should die within days when discharged to the environment in faeces.
For now, the 12 patients at the Academic Medical Centre in Amsterdam being given the bacteria are being kept in isolation. 鈥淭hey can鈥檛 go out, and all their faeces are collected, analysed, then destroyed,鈥� says Lothar Steidler, now at the University of Cork in Ireland, who heads the group pioneering the therapy.
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Steidler鈥檚 team chose the Lactococcus lactis bacterium because we already consume tonnes of it in dairy products such as mozzarella and Gouda cheeses. But rather than simply adding an extra gene to the bacterium, the interleukin-10 gene was used to replace a key bacterial gene called thyA. This codes for the enzyme needed to make thymidine, one of the building blocks of DNA.
In the gut thymidine is released as food is digested, so the modified bugs can flourish there even though they cannot make thymidine. But outside the gut, where there is little thymidine available, the bacteria soon die, as Steidler鈥檚 team has shown in experiments on mice and pigs (Nature Biotechnology, DOI: 10.1038/nbt840). It is also highly unlikely that the bacterium will acquire a copy of thyA from other bacteria, as the gene is found on the main bacterial chromosome, rather than one of the smaller pieces of DNA called plasmids that bacteria swap freely.
Patients take the bacteria as a coated pill that protects the bugs in the stomach before breaking open and disgorging its live cargo in the small intestine and colon. But it remains to be seen if the treatment will work. Direct injections of interleukin-10 itself have not succeeded, partly because the side effects are severe. The drug is also very expensive, costing 拢10,000 or more per patient per year.
So the idea of using cheap bacteria to deliver the drug to where it is needed is appealing. But there is no way to control the distribution of the bacteria within the gut, or how much interleukin-10 is produced, points out Joel Weinstock of the University of Iowa, who is also working on treatments for inflammatory bowel disease.鈥滻t鈥檚 a good idea, but we鈥檒l have to wait and see,鈥� he says.