Ghostwriting at Elite Academic Medical Centers in US

Jeffrey R.Lacasse, Jonathan Leo

PLOS Medicine; e1000230

Background:

Medical ghostwriting, the practice of pharmaceutical companies secretly authoring journal articles published under the byline of academic researchers, is a troubling phenomenon because it is dangerous to public health. For example, ghostwritten articles on rofecoxib probably contributed to “..lasting injury and even deaths as a result of prescribers and patients being misinformed about risks”. Study 329, a randomized controlled trial of paroxetine in adolescents was ghostwritten to claim that paroxetine is “generally well tolerated and effective for major depression in adolescents”, although data made available through legal proceedings show that “Study 329 was negative for efficacy on all 8 protocol specified outcomes and positive for harm”. Even beyond frank misrepresentation of data, commercially driven ghostwritten articles shape the medical literature in subtler but important ways, affecting how health conditions and treatments are perceived by clinicians. The ability of industry to exercise clandestine influence over the peer- reviewed medical literatures is thus a serious threat to public health.

In 2009, the institute of Medicine recommended that US-based academic medical centers enact policies that prohibit ghostwriting by their faculties. However, to date, there has been no systematic assessment of ghostwriting policies at academic medical centers. Since US based academic medical centers generate biomedical  research for a worldwide audience, we chose to conduct the first such investigation on elite US based academic medical centers generate biomedical research for a worldwide audience, we chose to conduct the first such investigation on elite US based academic medical centers.

Finding of Our Survey:

Of the 50 academic medical centers that we examined, ten(20%) explicitly prohibit ghostwriting. Of these ten, seven (14%) include some definition of ghostwriting in their policy, while three (6%) prohibit ghostwriting without defining the term. Many schools have an authorship policy that does not clearly ban all aspects of ghostwriting; the most common reason is a failure to require that all qualified authors be listed. Three academic medical  centers have stringent authorship policies that prohibit it in practice (by requiring both a substantive  contribution to qualify for authorship and that all who qualify for authorship  and that all who qualify for authorship be listed) but do not mention ghostwriting by name.

Microbe Gets Toxic Response

Nature; doi:10.1038/468741a

News:

Researchers question the science behind last week’s revelation of arsenic based life.

Days after an announcement that a strain of bacteria can apparently use arsenic in place of phosphorus to build its DNA and other biomolecules and ability unknown in any other organism some scientists are questioning the finding and taking issue with how it was communicated to non-specialists.

Many readily agree that the bacterium, described last week in Science and dubbed GFAJ-1, performs a remarkable feat by surviving high concentrations of arsenic in California’s Mono Lake and in the laboratory. But data in the paper, they argue, suggest that it is just as likely that the microbe isn’t using the arsenic, but instead is scavenging every possible phosphate molecule while fighting off arsenic toxicity. The claim at a NASA press briefing that the bacterium represents a new chemistry of life is at best premature, they say.

“It’s a great story about adaptation, but it’s not ET, says Gerald  Joyce, a biochemist at the Scripps Research Institute in La Jolla, California.

At the press briefing, Steven Benner, a chemist at the Foundation for Applied Molecular Evolution in Gainesville, Florida, who was invited to the event to offer outside comment used the analogy of a steel chain with a tinfoil link to illustrate that the arsenate ion said to replace phosphate in the bacterium’s DNA forms bonds that are orders of magnitude less stable. Not only would the organism’s DNA have to stay together in spite of the weaker bonds, says Benner, but so would all the molecules required to draw arsenate from the environment and build it into the genetic material. Co-authors of the paper, including Paul Davies, and astrobiologist at Arizona State University in Tempe, have contered that the arsenate bonds could be reinforced by specialized molecules, or that arsenic based life simply has a higher turnover for molecular disintegration and assembly than does conventional life.

The big problem, however is that the authors have shown that the organism takes up arsenic, but they “haven’t unambiguously identified any arsenic containing organic compounds”, says Roger Summons, a biogeochemist at the Massachusetts Institute of Technology in Cambridge. “And it’s not difficult to do,” he adds, noting that the team could have directly confirmed or disproved the presence of arsenic in the DNA or RNA using targeted mass spectrometry.

Some researchers suggest that the authors own data hint at an organism that is simply absorbing and isolating arsenate while making use of the trace phosphates in its environment. For one thing, says Joyce, the paper shows that  the organisms appear bloated and contain large, vacuole- like structures often a sign of sequestered toxic material. The arsenic grown cells were analysed in their resting phase, which requires less phospate for survival than does active growth, notes Joyce and cells grown in high concentrations of arsenate did not seem to contain any RNA possibly because RNA production had shut down to conserve phosphate. One calculation in the paper showed that the DNA in arsenate grown cells actually contained 26 times more phosphorus than arsenic.

Cap Binding and Immune Evasion revealed by Lassa Nucleoprotein structure

Nature; doi:10.1038/nature09605

Abstract:

Lassa virus, the causative agent of Lassa fever, causes thousands of deaths annually and is a biological  threat agent, for which there is no vaccine and limited therapy. The nucleoprotein of Lassa virus has essential roles in viral RNA synthesis and immune suppression, the molecular mechanisms of which are poorly understood. Here we report the crystal structure of Lassa virus NP at 1.80 Angstrom resolution, which reveals amino (N)-and carboxy(C)terminal domains with structures unlike any of the reported viral NPs. The N domain folds into a novel structure with a deep cavity for binding the m7GpppN cap structure that is required for viral RNA transcription, whereas the C domain contains 3’-5’ exoribonuclease activity involved in suppressing interferon induction. To our knowledge this is the first X-ray crystal structure solved for an arenavrial NP, which reveals its unexpected functions and indicates unique mechanisms in cap binding and immune evasion. These findings provide great potential for vaccine and drug development.

Gene Expression Divergence Recapitulates the Developmental hourglass model

Nature 468, 811-814; doi:10.1038/nature09634

Abstract:

The observation that animal morphology tends to be conserved during the embryonic phylotypic period(a period of maximal similarity between the species within each animal phylum) led to the proposition that embryogenesis diverges more extensively early and late than in the middle, known as the hourglass model. This patter of conservation is though to reflect a major constraint on the evolution of animal body plans. Despite a wealth of morphological data confirming that there is often remarkable divergence in the early and late embryos of species from the same phylum, it is not yet known to what extent gene expression evolution , which has a central role in the elaboration of different animal forms, underpins the morphological  hourglass pattern. Here we address this question using species  specific microarrays designed from six sequenced Drosophila species separated by up to 40 million years. We quantify divergence at different times during embryogenesis and show that expression is maximally conserved during the arthropod phylotypic period. By fitting different evolutionary models to each gene, we show that at each time point more than 80% of gene fit best to models incorporating stabilizing selection and that for genes whose evolutionarily optimal expression level is the same across all species, selective constraint is maximized during the phylotypic period. The genes that conform most to the hourglass pattern are involved in key developmental processes. These results indicate that natural selection acts to conserve patterns of gene expression during mid embryogenesis and provide a genome wide insight into the molecular basis of the hourglass pattern of developmental evolution.