No, this is not a post about another case of scientific misconduct (the sigma factor in transcription initiation published in Cell last October) but about Six Sigma, a process developed at Motorola in 1986 for measuring defects and improving quality of the production process (Motorola owns the trademark for Six Sigma). Read more at the excellent Wikipedia article – applying these principles could also help scientific projects, yea, yea.

The 3 Rs of regulating animal research are Refinement (to minimize suffering), Reduction and Replacement (to minimize the number of animals used). A Nature news feature now has a critical appraisal of current knockout projects where each of the 25,000 genes will be knocked out in the next future. Although current technology represent an advantage over recent undirected mutagenesis projects

… the number of mice needed to establish a line stretches from 50 to several 100. On top of this, another couple of 100 animals are needed for basic analysis of genetic make-up and phenotype…

Many genes cannot be knocked out – some knockouts may even be lethal.
We are also not so much interested in permanent destruction of genes in all tissues but in conditional and temporal shutdown of gene function.
And many researchers are not so much interested in the current 129 background than in BL6 (at least in immunology and allergology).
Finally (in human genetics) we are not dealing with knockouts but with multiple genomic variants of a gene. The question therefore is

Is the spirit of the knockout projects in line with [3R] principle[s]?

although I acknowledge that these industrial projects may generate many “nice to know” facts.

It was an interesting experiment that started on June, 1 in the Nature office: a first trial of of open peer review. Of the 10,000 papers received every year, 6,000 are immediately rejected and eventually 700 published after peer review. The result of the trial, however, is disappointing:

We sent out a total of 1,369 papers for review during the trial period. The authors of 71 (or 5%) of these agreed to their papers being displayed for open comment. Of the displayed papers, 33 received no comments, while 38 (54%) received a total of 92 technical comments.

The trial provoked some web traffic with approx. 800 page views/day. Welcome back to the altruism thread, the discussion may be followed at their blog, yea, yea.

In a previous paper I have questioned if LPS

nanogram exposure on the pulmonary epithelium will supersede the gram-wise exposure on the gut mucosa.

This may indeed work as now shown by Eyal Raz in a commentary in Nature Immunology where previous TLR studies

typically reproduce the splenic version of innate immunity (the spleen is used here as a metaphor for the sterile internal environment).

In the lung only the alveolar space is thought to be sterile while macrophages should not be in a constant state of activation (as inflammation would compromise gas exchange).

There are now several indicators for a lung-specific regulation of innate immunity: TLR9 is expressed in human plasmacytoid dendritic cells while TLR4 is only on myeloid DCs; TGFB-ß mediated crosstalk between alveolar macrophages and epithelial cells seems to be unique in the lung; in addition indeolamine induction or surfactant production is not found elsewhere. Yea, yea.

if you want to see Crison and me in the same stadium, you must bid him slacken his speed to mine, for I cannot run quickly, and he can run slowly.

(from Platons Protagoras dialogue English|German).

firstmonday has a wonderful paper “More, Faster, Better: Governance in an Age of Overload, Busyness, and Speed” basically arguing that the vast sources of information has a rather paradoxical effect: the abundance of information rather disconnects and distances us from ourselves and the world around us.

Immersed in a sea of media, information sources, technologies and devices, many of us are now becoming aware of the downside — some would say the dark side — of these powerful new modes of communicating and acting.

The mere number of papers being published even in my most genuine area of interest is impossible to monitor at the end of 2006 – bioscience looses more and more scientia. Although papers still have a “discussion” section, there is no more discussion as references are getting more and more eclectic.

The Levy paper in firstmonday is a “must read” – in particular the chapter on

Vannevar Bush, an American born in 1890, was trained as an electrical engineer and for the first part of his career worked as a professor and an administrator at MIT…. Bush was famous enough to appear on the cover of Time in April of 1944. Yet today he is best remembered not for his technical work or his contribution to winning the war, but for an article he published in the Atlantic Monthly in July, 1945, titled “As We May Think”

and what he says about two kinds of thought: routine or repetitive or logical thinking along an accepted groove – literature scan, arithmetic operations all that technical stuff that can be automated: In contrast there is mature, creative thought, deep, original thinking, reasoning – without any mechanical substitute. Levy makes the point that

Certainly the easy availability of information and the increasing pace of life can at times be empowering and even exhilarating, but too much stimulation can lead to numbing, a loss of focus, and withdrawal: it can dumb down, enervate and even stupefy.

the information overload (with less reliable, often questionable) information leads to a deprivation of mature thinking that severely affects now the academic world

Yet today’s universities — their faculty, students, and staff — are increasingly caught up in the current cultural frenzy; academics are now busier and more overloaded than ever before. The pressure on faculty to obtain outside funding is intense and increasing as the pool of available funds shrinks; time spent searching for potential funding sources, writing grant proposals, and shepherding them through intricate bureaucratic procedures is simply added on to the other expectations of the job…. increased student expectations that instructors should and will be available for consultation at all hours of the day and night, weekends included. E–mail has also made professors that much more reachable by the general public, the press, and academics at other institutions…

What can be done? Prescreening of relevant science by (institutionalised) editors or (anarchic) blogs? And by which criteria?

Rolf Zinkernagel in a commentary in Nature Immunology explains that today almost everything can be measured – and a nearly uncontrollable complexity often paired with weak detection methods renders experiments almost unrepeatable. His recommendations are

Most if not all experiments have limitations. Therefore researchers must think and argue and do experiments contrary to published results and against biases.

Nearly all studies need some funding; funding is controlled by peer review; peer review usually prohibits these experiments. Yea, yea.