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news Cash crisis Pet problem Deep thoughts Clean sweep US museums Could cats play a Commission sets out US to help replace threatened by leading role in the blueprint for US Russia’s nuclear economic downturn fight against SARS? ocean policy facilities p575 p576 p577 p578 Harmful potential of viral vectors fuels doubts over gene therapy Erika Check, Washington The troubled field of gene therapy was M. KAY dealt a fresh blow this week, after a study suggested that modified viruses used in some trials might cause health problems. The study, led by geneticist Mark Kay at Stanford University, California, examined a modified virus used in gene-therapy trials to treat haemophilia and cystic fibrosis. It revealed that the virus has the potential to cause the same problems that led to cancer in an unrelated gene-therapy trial last year. In gene therapy, doctors use a gutted virus as a ‘vector’ to transfer corrective genes into a patient’s cells. But if the vector stitches itself into a cell’s genes, it can cause the cell to mutate and become cancerous. This was demonstrated last year, when two children who had gene therapy for severe combined immunodeficiency disease (SCID) developed leukaemia (see Nature 419,545–546; 2002). Scientists are still trying to establish exactly why the SCID patients developed cancer, and will discuss the trial at this week’s Doctors at Stanford treat a haemophiliac in a gene-therapy trial — but how safe is the procedure? meeting of the American Society of Gene Therapy in Washington DC. But most agree which can be engineered to infect human cystic fibrosis trials integrates itself more that gene therapy was the cause. cells. In a paper published online on 1 June often into genes than it does into regions of Kay’s study focused on a vector made (H. Nakai et al. Nature Genet. doi:10.1038/ DNA that do not contain genes. The finding from an adeno-associated virus — an organ- ng1179; 2003), Kay and his colleagues show suggests that the vector could potentially ism that does not cause disease in people, but that the vector used in the haemophilia and cause the sort of cellular defects that led L Protests win reprieve for renowned medical lab Jim Giles, London already had a strong track record of would instead be decided by a task The UK Medical Research Council (MRC) collaborating with clinical researchers at force chaired jointly by himself and has shelved plans to close its largest various London hospitals, which employ Colin Blakemore, the University of laboratory, at Mill Hill in north London — a wider range of specialists than is found Oxford neuroscientist who will succeed at least for the time being. at Addenbrooke’s. him as chief executive in October (see In April, the MRC proposed that the Now their protests, which were Nature 423, 211; 2003). prestigious National Institute for Medical supported by several Members of Unlike the subcommittee behind the Research should move to Addenbrooke’s Parliament, seem to have hit home. In a original proposal, the task force will include Hospital in Cambridge, 50 miles away (see letter sent on 30 May to John Skehel, a scientists from Mill Hill itself, as well as Nature 422, 545; 2003). MRC officials said virologist and director of the Mill Hill from outside Britain. “This is a step forward that the move would save money and institute, MRC chief executive George in terms of consultation,” says Skehel. improve interactions between basic and Radda said that the council would abandon Despite their relief at the reprieve, clinical researchers. its original intention of reaching a decision researchers at Mill Hill say that they are still But the plan infuriated biomedical on the move by next month. worried that continuing uncertainty could researchers at Mill Hill, who said they Radda said that the future of the institute damage the institute. I NATURE | VOL 423 | 5 JUNE 2003 | www.nature.com/nature © 2003 Nature Publishing Group 573 news L to cancer in the SCID patients. But researchers caution that the vector used in the SCID trials, which was based Divisions sink US consensus on a retrovirus, is very different from the adeno-associated vector. For instance, effort on transgenic food retroviruses must insert themselves into human DNA to work, but adeno-associ- Jonathan Knight, San Francisco ated viral vectors integrate themselves An ambitious effort to hammer out an into the genome much less often. agreement between proponents and critics MONSANTO “Adeno-associated vectors clearly of agricultural biotechnology in the United have a better safety profile than retroviral States has ended in failure. vectors,” says David Russell, a geneticist at Two years of talks, convened in 2001 by the University of Washington in Seattle. the Washington-based Pew Initiative on “But we really can’t say yet that adeno- Food and Biotechnology, reached an impasse associated vectors won’t cause cancer.” late last month over the question of whether Kay’s team, which is running a gene- to ask Congress for legislation to strengthen therapy trial for haemophilia, tracked the regulations for transgenic food. adeno-associated viral vectors in mice. The 18-member panel was set up to pro- They extracted liver cells whose DNA duce detailed guidelines for safety standards contained the vector and then sequenced for genetically modified products. But the the DNA around the vector. They then ground rules for the panel required unani- Hard to swallow: regulations on transgenic food analysed the sequences to see whether they mous agreement on all issues under consid- proved a sticking point in US round-table talks. matched a known gene. The team found eration before any conclusions would be that 72% of the time, the vector had inter- made public. “It was an extremely ambitious problem by entrenching industry’s position. rupted a gene. Had it inserted itself ran- effort,” says Margaret Mellon, a panel mem- “The case is being made on the grounds that domly, the vector would have interrupted ber and director of the food and environ- the current regulatory process is safe,” says a gene no more than 40% of the time. ment programme at the Union of Concerned Robert Paarlberg, an expert in international Last August, Frederic Bushman and Scientists in Washington DC. “We were agricultural policy at Wellesley College near his colleagues at the Salk Institute for going for the brass ring, and we didn’t get it.” Boston. “The industry doesn’t want any sug- Biological Sciences in La Jolla, California, One issue that was contentious from the gestion that it isn’t.” suggested that retroviruses also insert start was whether new laws are needed to Panel member Richard Caplan, an envi- themselves into genes more often than guarantee the safety of transgenic food. The ronmental advocate with the US Public into other regions of DNA (A. R. biotechnology industry opposes the involve- Interest Research Group in Washington DC, Schroder et al. Cell 110, 521–529; 2002). ment of Congress in favour of minor admin- says that although the WTO suit was not dis- Such results are leading researchers istrative changes to the current approval cussed in the sessions, it could have been a to seek better ways to target vectors to process. But consumer and environmental factor. But Mike Rodemeyer, executive direc- specific regions of DNA, and to develop groups say that the present voluntary system tor of the Pew Initiative, says that he strongly vectors that don’t integrate into DNA at is inadequate and needs a legislative fix. Panel doubts whether it made any difference. all. But in the meantime, Kay says that he members confirm that disagreement on this The panel’s final report, issued on 30 has taken numerous precautions to pro- point was critical to the failure of the process. May, left open the possibility of reconvening tect the 14 haemophiliacs he has treated. Some observers suggest that the recent in 12–18 months’ time. If consumers outside “I don’t think we need to modify any- trade complaint filed at the World Trade the United States continue to resist trans- thing at this point,” Kay says. “But this is Organization (WTO) by the United States genic food, US food exporters might feel a risk we’ll have to address before the against the European Union (see Nature 423, pressure to conform to tougher regulation, vector is in widespread use.” I 369; 2003) might have contributed to the some panel members say. I UK universities face star treatment in funding revamp Jim Giles, London be the sum of the scores of its individual shorter review process. That idea has drawn The seven-point scale used to assess research researchers, providing a measure of the fire from some of the smaller universities. in British university departments could be overall volume of quality work produced. “It is divisive,” says Mike Saks, pro-vice- scrapped under plans unveiled on 28 May. Roberts says that individual ratings would chancellor for research at the University of The Research Assessment Exercise (RAE), not be published, but sceptics doubt whether Lincoln. The university received just £250,000 a five-yearly audit of research, is widely the scores could be kept from researchers. this year from the funding councils, but Saks credited with strengthening British science. “How will that information be denied them?” says it has begun a major drive to improve But scientists have complained that the asks Keith Peters, an immunologist at the its research and doesn’t want to be put in a rankings are sometimes arbitrary, and give University of Cambridge and president of second class of institutions.

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