news20091114nn1

[naturenews] from [nature.com]

[naturenews]
Published online 13 November 2009 | Nature | doi:10.1038/news.2009.1083
News
Australian agency moves to calm climate row
Researcher will be allowed to publish his paper after making 'tiny' changes.
Stephen Pincock

{{Publication of a paper on cap-and-trade has been held up by CSIRO.}
Malcolm Paterson/ CSIRO}

An Australian researcher involved in a censorship controversy will be allowed to publish a paper critical of cap-and-trade systems for controlling carbon emissions — but only after some changes are made to wording, the country's science agency has said.

Clive Spash, an ecological economist at the Commonwealth Scientific and Industrial Research Organization (CSIRO) in Canberra, had an invited paper on the failings of emissions-trading schemes accepted by the journal New Political Economy earlier this year. But the acting chief of his division subsequently wrote to the editors telling them that the paper was being withdrawn because it had not passed internal processes (see 'Australian agency denies gagging researchers').

With Australia's government battling to pass emissions legislation, accusations that the agency was trying to muzzle climate researchers made headlines.

But after Spash met with CSIRO chief executive Megan Clark on 9 November, the two reached an agreement that the paper could be published with some rewording. "We had a productive talk," Spash says. "I was told by the chief executive that her changes would be tiny, consisting of a few words or phrases. That sounds as if it would be acceptable."

A spokesman for the agency, Huw Morgan, confirmed that Clark told Spash the article was publishable under CSIRO rules with "minor but important" changes. He said Spash would see the proposed changes by close of business today.

Chopping and changing

The issue centres on the charter under which the CSIRO, a statutory authority, operates. That charter allows agency researchers to discuss their results, but says they "should not advocate, defend or publicly debate the merits of government or opposition policies".

Spash told Nature that Clark agreed with "my own opinion that the paper did not breach the CSIRO charter or policy in any substantive fashion. This reversed the decision statements previously issued to me by senior managers wishing to cut 75% or more of the paper."

{{“The paper was therefore submitted to the journal, with the express permission of the acting chief of division.”}
Clive Spash
CSIRO}

The paper analyses emissions-trading schemes, economists' claims for them, and the implications of their design. "There is no detail on, nor analysis of, the current proposals by the Australian government or opposition parties," says Spash.

When he first alerted his CSIRO bosses to the paper, they considered it to be politically sensitive and in need of robust review, Spash said. Normally, papers produced by the agency are reviewed internally before being sent for external review. But Spash says he and his co-author Andrew Reeson were told they should send the paper straight away for review by the journal even though the internal review had not concluded.

"The paper was therefore submitted to the journal, with the express permission of the acting chief of division, prior to completion of the internal referee's reports," Spash adds. "Both internal referees recommended publication a few weeks after submission to the journal."

Spash says the journal accepted a revised version of the paper in June. He told the acting division chief this, but two weeks later was informed that the article could not be published.

Speak truth to power?
The episode has caused debate in Australia about whether CSIRO scientists should have the same freedoms as university academics.

Michael Borgas, president of the CSIRO's staff association, has backed the current system, telling The Australian newspaper that most of the agency's researchers "find they are helped by CSIRO to directly engage with the political process by getting their research into the heads of [ministers and the bureaucracy], rather than by publishing in academic journals".

Meanwhile, CSIRO has moved to further tighten its grip on scientists' freedom to speak out, rolling out a new policy over recent weeks that requires researchers "to use their CSIRO affiliation on all publications that arise from research work they do as an employee with CSIRO," spokesman Huw Morgan said. Morgan said it would be extended across the agency by early 2010.

Spash hopes his case will highlight the need for openness and public engagement. "This does not mean scientists becoming political activists or advocates," he says. "It does mean being prepared to make and defend logical arguments and being prepared to explore moral and ethical issues."

"Institutions are today facing the reality of a new mode of operation at the science–policy interface," he adds. "My hope is that recent events have shown they must grasp this challenge rather than falling back into a mode of operation which is long outdated."


[naturenews]
Published online 13 November 2009 | Nature | doi:10.1038/news.2009.1085
News
Selective sequencing solves a genetic mystery
Examining only protein-coding genes finds cause of Miller syndrome.
Elie Dolgin

Targeted sequencing of the entire protein-coding portion of the human genome has for the first time discovered the cause of a rare genetic disorder.

"This technology is incredibly promising," says James Kiley, director of the division of lung diseases at the National Heart, Lung and Blood Institute in Bethesda, Maryland, which partly funded the work. "It's giving us a more efficient way to identify the causal genetic factors of disease."

Protein-coding genes make up only about 1% of the human genome, but they harbour the bulk of the mutations that contribute the most to disease. So, rather than sequencing entire genomes, many researchers are starting to decode only the protein-coding exons — collectively called the 'exome' — to make genetic inferences at a fraction of the cost of whole-genome sequencing.

In August, a team led by Jay Shendure and Sarah Ng at the University of Washington in Seattle provided the first proof-of-principle that this approach could detect the genetic culprits behind single-gene, or Mendelian, diseases. The researchers sequenced the exomes of 12 unrelated individuals, four of whom had a rare, inherited disorder called Freeman–Sheldon syndrome. Although the genetic defect behind the disease was already known, the technique zeroed in on the exact gene responsible for the disease, demonstrating that it was feasible to sort out the genetic signal from more than 300 million bases of DNA noise¹.

"The primary criticism of that paper is that we knew the answer and we were basically showing it could be done," says Shendure. "Here, we're extending that to something where we didn't know the answer."

Tip of the iceberg

{{Miller syndrome was first described 30 years ago but its cause was a mystery.}
Nature Genet., S. B. Ng et al}

Shendure and his colleagues have now sequenced the exomes of two siblings and two unrelated individuals who all suffered from a single-gene disorder called Miller syndrome, which is characterized by facial malformations and limb abnormalities, such as a cleft palate and absent or webbed fingers and toes. Although the disease was first described 30 years ago, its genetic basis has remained elusive.

The researchers compared the exomes of Miller-affected individuals to exome sequences from eight healthy, unrelated individuals. This approach flagged a single candidate gene called DHODH, which encodes an enzyme that is essential for making some of the building blocks used in DNA and RNA. Shendure's team then directly sequenced DHODH in four more Miller-affected individuals and found that they too all had mutations in this gene. No similar mutations were found in 100 unaffected individuals. The findings are published online today in Nature Genetics².

"This is the first demonstration of whole-exome sequencing for a new disease-gene discovery," says Richard Lifton, a geneticist at Yale University School of Medicine in New Haven, Connecticut, who was not involved in the work. This first discovery is only the tip of the iceberg, he adds. "I think there are large classes of Mendelian traits that will be found by whole-exome sequencing."

Lifton also notes that exome sequencing will be useful as a clinical tool. In October, Lifton and his colleagues used the technique to diagnose a five-month-old child with a mysterious genetic illness. They found that the infant, who was suffering from persistent dehydration and a lack of weight gain, had a mutation in a gene that caused intestinal problems due to congenital chloride diarrhoea, not in a kidney-associated gene as physicians had originally suspected³.

Shendure is confident that exome sequencing can reliably uncover genes that are responsible for relatively simple, single-gene disorders. The big challenge moving forward, he says, is to show that the method can tease apart the genetic basis of more-complex diseases in which two or more genes are involved. "That's by no means a given," he says. "This is going to be hard."

References
1. Ng, S. B. et al. Nature 461, 272-276 (2009).
2. Ng, S. B. et al. Nature Genet. advance online publication doi:10.1038/ng.499 (2009).
3. Choi, M. et al. Proc. Natl Acad. Sci. USA 106, 19096-19101 (2009).