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[naturenews] from [nature.com]

[naturenews]
Published online 19 November 2009 | Nature | doi:10.1038/news.2009.1099
News
Europe puts brakes on fusion project
Firing up ITER in 2018 is not feasible, warn council delegates.
Geoff Brumfiel

{{Fusion dreams, delayed once more?}
ITER Organization}

The European Union (EU) is backing away from a 2018 start date for ITER, a multi-billion-euro fusion reactor under construction in the south of France.

At an ITER council meeting on 18–19 November, which was held near the reactor's site in St Paul-lez-Durance, delegates from the EU told the project's six other member states that the start date was no longer realistic, according to a source close to the negotiations. The two-day meeting concluded earlier this afternoon.

Catherine Ray, a spokesperson on science and research for the European Commission in Brussels, declined to answer Nature's questions about changes in ITER's schedule, but reiterated Europe's support for the project. "Our guiding objective is to ensure a sustainable success for ITER at reasonable costs and with an acceptable level of risk," she says.

ITER is a massive experiment to prove the viability of nuclear fusion as a power source. When completed, superconducting magnets will squeeze a plasma of heavy hydrogen isotopes — deuterium and tritium — to temperatures in excess of 150 million °C. The resulting fusion reaction should produce ten times the power consumed in the process of creating the plasma.

The EU is by far the largest participant in the project. It will pay roughly 45% of the construction costs of ITER, while the other participants — China, India, Japan, Russia, South Korea and the United States — will each provide roughly 9%. The costs were originally budgeted at around €5 billion (US$7.4 billion) when the agreement to build ITER was signed in 2006, but they are now expected to be roughly double that figure by the time the reactor is built.

Under a tentative agreement reached in June, ITER's council approved 2018 as the date for 'first plasma' being generated inside the giant device. But some had worried that the EU was having trouble coming up with the additional funds needed to start construction (see 'Fusion delays sow concern').

There is also concern among European's involved in the project that the present schedule might be risky, according to Günther Hasinger, the scientific director of the Max Planck Institute of Plasma Physics in Garching, Germany. The EU is responsible for buildings and other major infrastructure at the 180-hectare ITER site. "All the big European components are needed early on," he says, warning that the 2018 date leaves little margin for error. "It's an extremely risky schedule."

The reaction of the other member states to the EU announcement is likely to be mixed, says Stephen Dean, president of Fusion Power Associates, a fusion-advocacy group based in Gaithersburg, Maryland. Senior officials at the US Department of Energy, which is responsible for that country's contributions to ITER, have publicly complained about the long timeline of the project. But Dean says that many researchers in the United States who are involved in ITER have been worried that the project might not meet its current schedule.

ITER's council has now tasked the project with working out two possible start dates for the project: one early and one late, according to Neil Calder, chief spokesperson for ITER. Calder says that the organization should be able to deliver the new dates by February 2010, but could not say whether 2018 would be one of the options. Planning a project as complex as ITER is difficult, he says. "I think it is worth taking the time to get it right."


[naturenews]
Published online 19 November 2009 | Nature | doi:10.1038/news.2009.1097
News
Gene silencing predicted to improve drug manufacturing
Biotech firm hopes to use RNA interference to boost drug yields.
Elie Dolgin

{{Chinese hamster ovary cells: the workhorse of the biological drug market.}
Nikon MicroscopyU}

The burgeoning science of RNA interference (RNAi) — touted as the next frontier in pharmaceutical treatment — is now being directed at increasing the efficiency of drug manufacturing processes.

Alnylam Pharmaceuticals, a biotech firm based in Cambridge, Massachusetts, already uses RNAi in its drug-discovery research. The technique involves using small RNA molecules to reduce the activity of specific genes.

Now, the company plans to use the technology to improve the production of protein-based medicines, monoclonal antibodies, vaccines and other biological drugs, also known as biologics. On 12 November the company announced a new venture, called Alnylam Biotherapeutics, to develop the technology and partner with biopharmaceutical manufacturers interested in using the approach to improve their drug-producing cell cultures.

John Maraganore, Alnylam's chief executive, says that the company has sequenced the genome of Chinese hamster ovary (CHO) cells, the most widely used cell line in the US$100-billion biologicals market. Using the genome, Alnylam has designed small RNAi molecules that can extend the lifespan of the cells — and potentially boost the yield of the drugs they produce.

Silencing two genes in the cell-death pathway, for instance, extended the life of the cells by about 40%; targeting one involved in lactic-acid metabolism boosted lifespan by 60%. "We have already shown that we can harness RNAi technology to alter the cell to live longer and do more of what it needs to do," Maraganore says.

The approach is not without precedent. A handful of researchers, including Zhiwei Song, an engineer at the Bioprocessing Technology Institute in Singapore, have shown that RNAi can more than double the quantities of proteins secreted by CHO cells in the laboratory¹. The challenge, says Song, will be to extend the technique to large-scale cultures in bioreactors that can hold tens of thousands of litres of CHO cells.
"A means to enhance the expression of biologics without changing the master cell banks would certainly be of great industry interest," says Derek Ellison, chief operating officer of Eden Biodesign, a contract biopharmaceutical manufacturing company in Liverpool, UK. First, though, Alnylam would have to prove that RNAi doesn't introduce any impurities or alter the quality of the drugs, he says. Companies would also have to redevelop their downstream processing to cope with the increased quantities of product.

Suh-Chin Wu, a cell-culture bioengineer at the National Tsing Hua University in Taiwan who recently wrote a review article² about using RNAi in CHO cells, doesn't expect many problems with quality or safety. RNAi-based medicines, which are currently in multiple late-stage clinical trials, have not caused any serious side effects in patients. So adding the small RNA molecules to a cell-culture system should not pose any health risks or add any regulatory hurdles, he says.

Even if the process works, however, the technology might not be profitable, cautions Tillman Gerngross, a biological engineer at Dartmouth College in Hanover, New Hampshire. Manufacturing makes up only a sliver of the total cost of drug production, and "making more stuff cheaper is no longer something that people are willing to pay a lot of money for", he says. Instead, RNAi should be used to improve the quality and potency of biologicals, Gerngross says.

Alynlam is starting to do just that. Maraganore says the company is looking beyond cell viability and working to boost the secretion efficiency of recombinant proteins and to alter various properties of biologicals to make them more active. "It's a broad platform that can be harnessed in many ways," he says.

References
1. Lim, S. F. et al. Metab. Eng. 8, 509-522 (2006). | Article | PubMed | ChemPort |
2. Wu, S.-C. Biotechnol. Adv. 27, 417-422 (2009). | Article | PubMed | ChemPort |