Category Archives: Philosophy
Epistemic disruption
A new First Monday paper examines our modern publishing system that has been driving the art of doing science into a primitive strategy of making impact points.
These disruptive forces are represented by changing technological, economic, distributional, geographic, interdisciplinary and social relations to knowledge. The article goes on to examine three specific breaking points. The first breaking point is in business models — the unsustainable costs and inefficiencies of traditional commercial publishing, the rise of open access and the challenge of developing sustainable publishing models. The second potential breaking point is the credibility of the peer review system: its accountability, its textual practices, the validity of its measures and its exclusionary network effects. The third breaking point is post–publication evaluation, centered primarily around citation or impact analysis. We argue that the prevailing system of impact analysis is deeply flawed.
yea, yea.
A better search engine for science?
New rumors say about Wolfram alpha
In this respect it is vastly smarter than (and different from) Google. Google simply retrieves documents based on keyword searches. Google doesn’t understand the question or the answer, and doesn’t compute answers based on models of various fields of human knowledge.
…
or those who are more scientifically inclined, Stephen showed me many interesting examples — for example, Wolfram Alpha was able to solve novel numeric sequencing problems, calculus problems, and could answer questions about the human genome too.
I have applied for a test account as I am interested in methods how to deal with genomic and all the other pentabyte of data — we urgently need a paradigm shift as single genome prices will go down to 1000 €. Continue reading A better search engine for science?
Still some time left?
There are many interesting objects at the virtual Science Museum covering the long history of medicine. The site is currently down but will hopefully be restored this night.
Is the Nobel prize predictable?
To be a Nobel candidate may be predictable if I am reading correctly a paper on archiv.org. The “traditional” impact factor is largely useless
as it ignores the importance of citing papers: a citation from an obscure paper is given the same weight as a citation from a ground-breaking and highly cited work
It may be, however, that the (PageRank derived) CiteRank is holding some promises – giving weight by whom you are cited. In this case, even a 100 citation paper can lead to a Nobel prize.
But is it predictable to get a Nobel prize candidate? Certainly not. I agree with a news feature about a science manager who
recently read Outliers, a book in which Malcolm Gladwell makes the case that
exceptional people get where they are partly because of the exceptional circumstances in which they find themselves, rather than through exceptional ability or sheer hard work.
Yea, yea.
Show off – the most important bias in research
A new editorial in PLoS medicine suggests five ways how trust in publications can be reestablished:
First, editors themselves should recognize and declare their own competing interests. Continue reading Show off – the most important bias in research
Pray tell us what you do
I already suspect that science has more to do with believes than religion. However, only very recently I came across this paper (when working on eosinophils) that stretches this view to its limits: “Eosinophil cells, pray tell us what you do!” Or is that a new incarnation of Spinoza’s God in Nature?
Interrupt yourself
or should I have said that science is nothing more than an extension of the senses? Or that most of our scientific output is done by autopilots?
Peer review – a charade?
quoting from an email this afternoon:
Only 8% members of the Scientific Research Society agreed that “peer review works well as it is.” (Chubin and Hackett, 1990; p.192).
“A recent U.S. Supreme Court decision and an analysis of the peer review system substantiate complaints about this fundamental aspect of scientific research.” (Horrobin, 2001).
Horrobin concludes that peer review “is a non-validated charade whose processes generate results little better than does chance.” (Horrobin, 2001). Continue reading Peer review – a charade?
Darwin and successors
Here is a picture the original 1859 edition of the “Origins” while I still wonder if this book is about the origins or about the transitions of species.
That may be understandable as I am currently reading David Berlinski’s 2008 book “The Devil’s Delusion”. His (English) Wikipedia entry is not Continue reading Darwin and successors
La gaya scienza
Dieter Hattrup pointed me today to Nietzsche
Der tolle Mensch sprang mitten unter sie und durchbohrte sie mit seinen Blicken. Wohin ist Gott? rief er, ich will es euch sagen! Wir haben ihn getödtet, ihr und ich! Wir alle sind sein Mörder! Aber wie haben wir diess gemacht? Wie vermochten wir das Meer auszutrinken? Wer gab uns den Schwamm, um den ganzen Horizint wegzuwischen? Was thaten wir, als wir diese Erde von ihrer Sonne losketteten?
But see also Nietzsche’s account to all Darwin admirers (page 119 of Hattrups book)
Die Behauptungen Darwin’s sind zu überprüfen – durch Versuche! Ebenso die Entstehung höherer Organismen aus den niedersten. Es müssen Verscuhe auf 1000de von Jahren hin geleitet werden! Affen zu Menschen erziehen!
Gaya scienza is close to todays’ synthetic biology, yea, yea.
Cargo Cult Science
Robert Feynman introduced that term 1974 in his Caltech commencement – an analogy to natives to Samoa who created mock airports Continue reading Cargo Cult Science
Never complain never explain
Giovanni Abbadessa, Roberto Accolla, Fernando Aiuti, Adriana Albini, Anna Aldovini, Massimo Alfano, Guido Antonelli, Courtenay Bartholomew, Zvi Bentwich, Umberto Bertazzoni, Jay A. Berzofsky, Peter Biberfeld, Enzo Boeri, Luigi Buonaguro, Franco M. Buonaguro, Michael Bukrinsky, Arsène Burny, Continue reading Never complain never explain
A passion for precision
The title is borrowed from the opening Lecture of Theodor Hänsch on July, 7th, 2006 at the The Euroscience Open Forum in Munich and the Nobel lecture on December 8, 2005 [video] – one of the real science heroes.
(essay written 1/10/2009)
With a never ending stream of genetic association studies in allergy research we are facing severe problems as most of these studies are never reproduced 1. The Lancet editors already think that genetic association is “in danger of becoming a rather dirty word” 2 with even consensus recommendations are not being able to dam up this flood 3, 4. Should we rethink about reasons and consequences 5,6 ?
The Inevitable. The many contradictory results are frequently explained by genetic heterogeneity across populations. There are indeed good examples where populations differ in genetic terms. Lactase variants for example show a clear European South / North gradient. Estimating the genetic risk in an additional populations for replication, however, may have only limited value if population specific risks are of such an enormous importance – which may be particular relevant for founder populations and for rare variants. A recent family study 7 found a rare mutation in filaggrin (FLG) associated with atopic dermatitis (AD). Every replication study will depend on the fact that we are sampling enough FLG carriers from the population as well as enough AD patients while replication would fail in black-skinned AD patients (where FLG variants are absent). Non-replication therefore does not necessarily refute a true association while on the other hand replication in a further sample does not sort out a biological relevant association from a chance finding.
Another frequently invoked argument for non replication is phenotypic heterogeneity in complex diseases. Lacking precision in how outcomes are defined and how they are validated may explain non-replication in particular when the phenotype under interest relies on a simple diagnosis only and ignores the underlying QTLs. But there may be less doubt about a positive association like that of FLG and AD when looking at linkage scores, functional properties of the truncated profilaggrin, the general skin physiology, other irritant effects and finally the itchy and dry skin in these patients. Many genetic associations, however, are ignoring the biological context (as well as all Bradford-Hill criteria of causality) and have entered the (never) ending replication loop. Curiously, some associations being published also in high impact journals do not received any interest at all 8. Replication of genetic studies is not an art 9 – it is science or no science at all.
The evitable. Even if we assume for a moment that nature leaves us a detectable genetic risk in complex diseases (that is being worthwile to be found) the field is plagued by studies that are poorly planned, biased sampled, sloppy analysed and botchy reported. Although being accepted on a theoretically level 10, 11 these problems are tacitly ignored. While running a reference database of genetic association over many years, we recognized an increasing number of studies lacking precision in reporting.
No doubt, errors occur while writing and typesetting of manuscripts, however, it seems that careful writing and copy-editing of printed material has become unfashionable. As a consequence a recent commentary 12 defined scientific misconduct in a new way – as a continuum ranging from honest errors to outright fraud. While the impact of fraud in the field of genetic association studies will be low (due to its low prevalence), the impact of inappropriate research conduct is being high (due to the high prevalence). There are many ways how genetic associations are being distorted by ignoring previous work, insufficient reporting of methods, suppressing inconsistent own data, poor adjustment of confounders, unreported multiple testing, frouzy tables, wording, and references. Accurate reporting may be an ethical duty as this “is not merely a failure to satisfy a few highly critical readers. It not infrequently makes the data that are presented of little or no value.” (http://www.plos.org/cms/node/371). Unfortunately the overloading of referees with ever increasing review requests may be a reason that these errors are not being detected anymore. The number of publications doubled during the last decade while the number of journals basically remained the same.
Decades ago, the bulk of scientific work was done by single researchers. The dusty folios in the libraries that survived from that time list just one author (at the end and not at the beginning of a paper) who had the ultimate responsibility. He would get all credits for his achievements – or all malice for the failure. When researching the obvious errors in some current association papers I have found an “impersonation” effect: The first author moves his responsibility to a statistician who claims that the data administrator had failed while the data administrator does not feel to be responsible for genotyping and so on: “Success has many fathers while failure is an orphan”. It is unacceptable that even papers withtwo dozen errors are never retracted13.
A solution. The field probably requires a greater investment of resources and more careful attention to details. A way out could be joint MD/PhD programs where investigators will learn to deal with clinical protocol, the laboratory work, the data analysis, how to interpret and validate the conclusions. It can be taught in the class room (and by example) how to ask the right clinical question, to perform accurate laboratory work, to check the integrity of data, to perform an optimal analysis, to develop a proper interpretation and to adopt a good writing style 14. We need quality assurance courses covering all critical steps but also teaching scientific accurateness and research ethics.
Also post-publication strategies could be discussed 15. As already mentioned most erroneous papers are neither corrected nor retracted, a bias called by Jim Giles to be “reluctant to have my name attached to negative comments” 16. The comment function in BMC journals, the respond button at BMJ and the eLetter function at PLOS journals nevertheless may be a some first step into a more open discussion of research failure.
It is timely to develop, implement and supervise good scientific practice also for genetic association studies in allergy research. The hunt for impact has compromised the field in an unfortunate manner where the “public´s trust in science and scientists is deteriorating” 17. Most researchers agreed during a recent web survey that most published research findings are wrong 18. We need more passion for precision to get back the trust in our science.
Cited References
1. Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG (2001) Replication validity of genetic association studies. Nat Genet 29:306-309
2. Lancet T (2003) In search of genetic precision. The Lancet 361:357
3. NN (2005) Framework for a fully powered risk engine. Nat Genet 37:1153
4. Cordell HJ, Clayton DG (2005) Genetic association studies. Lancet 366:1121-1131
5. Buchanan AV, Weiss KM, Fullerton SM (2006) Dissecting complex disease: the quest for the Philosopher’s Stone? Int J Epidemiol 35:562-571
6. Edwards JH (1999) Unifactorial models are not appropriate for multifactorial disease. Bmj 318:1353-1354
7. Smith FJ, Irvine AD, Terron-Kwiatkowski A, et al. (2006) Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet 38:337-342
8. Zhang Y, Leaves NI, Anderson GG, et al. (2003) Positional cloning of a quantitative trait locus on chromosome 13q14 that influences immunoglobulin E levels and asthma. Nat Genet 34:181-186
9. Kabesch M (2009). The art of replication. Thorax 64:370-371
10. Spilker B (1991) Guide to Clinical Trials. Lippincott Williams and Wilkins:24ff
11. Skrabanek P. M, J. (1990) Follies and Fallacies in Medicine. Prometheus, Buffalo
12. Nylenna M, Simonsen S (2006) Scientific misconduct: a new approach to prevention. Lancet 367:1882-1884
13. Kabesch M, Peters W, Carr D, Leupold W, Weiland SK, von Mutius E (2003) Association between polymorphisms in caspase recruitment domain containing protein 15 and allergy in two German populations. J Allergy Clin Immunol 111:813-817
14. Anonymous (2005) Good data need good writing. nature immunology 6:1061
15. Bracken MF (2005) Genomic epidemiology of complex diseases: The need for an electronic evidence-based approach to research synthesis. American Journal of Epidemiology 162:297-301
16. Giles J (2006) The trouble with replication. Nature 442:344-347
17. Neill US (2006) Stop misbehaving! Journal of Clinical Investigation 116:1740-1741
18. Ioannidis JP (2005) Why most published research findings are false. PLoS Med 2:e124
Our politicians, our governments? Always years behind
The new Edge Magazine has the annual question 2009 online
New tools equal new perceptions.
Through science we create technology and in using our new tools we recreate ourselves. But until very recently in our history, no democratic populace, no legislative body, ever indicated by choice, by vote, how this process should play out.
… While science may or may not be the only news, it is the news that stays news.
And our politicians, our governments? Always years behind, the best they can do is play catch up.
But unfortunately it continues Continue reading Our politicians, our governments? Always years behind