Tag Archives: Science + Philosophie

Delusion or poor scientific hypothesis

Delusion is a common symptom of paranoid schizophrenia ICD10 F20.0, usually combined with hallucinations (either auditory – noises or voices, visual or other perceptions of smell or taste). The most common paranoid symptoms are delusions of persecution, reference, exalted birth, special mission, bodily change, or jealousy. It has been most impressing (and harrowing) to see these patients as a medical student in Vienna at Baumgartner Höhe. Of course I visited Berggasse 19 but there have been more pioneers in Vienna like Krafft-Ebing).

We are arriving now at my main question: What is the difference between delusion and a scientific hypothesis? This question stems from a recent appraisal of the “TH17 revision” of the TH1/TH2 hypothesis by Lawrence Steinman

A historical perspective on the TH1/TH2 hypothesis is illuminating, both for its insights into important immunological phenomena and for its revelations about how groups of highly trained intellectuals, in this case immunologists, can adhere to an idea for so many years, even in the face of its obvious flaws.

He refers mainly to predictions of EAE outcomes – as an allergologist I could add more examples where the simple TH1/TH2 paradigma did not work. What is the difference between delusion and a scientific hypothesis? In my opinion the answer is context dependent as there is not so much difference – delusion will not be so persistent over time (although it is nearly impossible to convince somebody that he is captured by a delusion) while a poor hypothesis is usually more persistent (but there is a good chance to convince somebody that a hypothesis is wrong). Steinman also has some advice

We should not become fixated on the hypothesis, as if it were a ‘Law’, which in any case may fall in the face of new data that such a Law cannot explain. Most importantly, we should not ignore aberrant data that cannot be explained by a concept, whether it is deemed a Law or, more modestly, a Hypothesis. We should always be careful to explain those quirky aberrant points in the data and those annoying blemishes and flaws in the scientific theory. They may be hiding a tremendous new insight.

Meeting abstract versus full paper

JACI has an interesting letter comparing the number of meeting abstracts and the subsequent publication of a full paper. It seems that there is a large variation from from 11% to 78% – does this really mean that at some meetings half of the talks is not worth to write them up? This would explain why at some conferences nobody is taking notes – I am usually playing sudoku, backgammon or go but have also interesting podcasts with me.

Poll: Are most published research findings wrong?

–Day 5 of Just Science Week–

John Ioannides has published a rather influential paper (that will not so often be cited as read): “Why Most Published Research Findings Are False”. In principle his arguments are (numbering by me):

1. a research finding is less likely to be true when the studies conducted in a field are smaller
2. when effect sizes are smaller
3. when there is a greater number and lesser preselection of tested relationships
4. where there is greater flexibility in designs, definitions, outcomes, and analytical modes
5. when there is greater financial and other interest and prejudice
6. and when more teams are involved in a scientific field in chase of statistical significance

According to good scientific practice, this could be tested – the only problem is to recognize if the result of a single study is wrong. To be continued in 20 years…

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Less is more

–Day 3 of Just Science Week–

Peer review certainly plays a major role in assuring quality of science. There are many positive aspects of peer review (plus a few disadvantages like promoting mainstream). Systematic research on peer review, however, has been largely absent until 2 decades ago; after 5 international conferences on peer review there is now also the WAME association of journal editors. Over the years, I have experienced the “cumulative wisdom” thrown at my own papers and of course developed my own style when doing reviews. Last week PLOS medicine published an interesting study who makes a good peer review:

These reviewers had done 2,856 reviews of 1,484 separate manuscripts during a four-year study period, and during this time the quality of the reviews had been rated by the journal’s editors. Surprisingly, most variables, including academic rank, formal training in critical appraisal or statistics, or status as principal investigator of a grant, failed to predict performance of higher-quality reviews. The only significant predictors of quality were working in a university-operated hospital versus other teaching environment and relative youth (under ten years of experience after finishing training), and even these were only weak predictors.

The first finding may be unimportant for non-medics but the second may apply to a larger audience. What I fear – and that is usually not mentioned in the current discussion – that the peer review system is slowly suffocating. The willingness to do this (unpaid & extra) work is going down as papers (at least in my field) are produced more and more an industrial mass production level. I am getting a review request nearly every second day while I do need between 30 minutes and 3 hours for a paper. So, less is more.

Addendum

For a follow up go to sciencesque, a scenario how science in the post-review phase will work.

Enter without knocking if you can

This was posted at the door of Max Delbrück (1906-2006) in Pasadena – and quoted from the wonderful biography of E.P. Fischer his last Ph.D. student.
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“Licht und Leben” (or “light and life”) is a wonderful narrative that I really enjoyed, with a lot of informative figures and tables.
I wonder why this biography never appeared in English, why neither institutes in Berlin, Cologne or Constance (where Delbrück teached) are even linking to it. E.P. Fischers book tells the story about an interesting man dedicated to science – who learned physics and applied sound principles to biology. “Enter without knocking” does not have any special meaning (as E.P. Fischer confirmed me) it was simply a rough-running door. Besides the biographical sketch and the detailed description of phages and phycomyces (p15) there are many moments in time that I really liked very much.
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Hershey (with whom he shared the Nobel in 1969) should give a lecture and asked about the background of the audience. Max Delbrück answered by a postcard 6/1/1943: think of “complete ignorance and infinite intelligence” – the lecture became a success.
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Delbrück always emphasized (p 148) that data should only be augmented by those who can put old data into new hypotheses. He even said “enough data” as thinking about current experiments is being as important as doing new ones. Both, thinking and doing experiments, should even be more important than publishing (his lifetime list has 115 items). Writing up results should serve as a method to connect what is currently known and what will be known. Delbrück even suggested to spend – “one day per week without pipettes”.
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From an interview (p 240): “Genetic engeneering may possibly be a large thread for the future but possible also the biggest hope”.
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Delbrück was a great admirer of Eliot, Rilke and of Beckett. Samuel Beckett in “Waiting for Godot” probably inspired “Licht und Leben” (p 260): “We give birth astride a grave, the light gleams an instant, then there is night once more.”

Addendum

Page 239 contains a mystery: In 1978 Delbrück gave a lecture at Caltech where he wanted to include a citation from Kierkegaard: “Wissen ist eine Sache der Einstellung, eine Leidenschaft, eigentlich eine unerlaubte Einstellung. Denn der Zwang zum Wissen ist wie Trunksucht, wie Liebesverlangen, wie Mordlust, in dem sie einen Charakter aus dem Gleichgewicht wirft. Es stimmt doch gar nicht, daß der Wissenschaftler hinter der Wahrheit her ist. Sie ist hinter ihm her. Er leidet unter ihr.” Delbrück, however, could not find the correct source, even announced to pay 50$ for it. I also looked at my library but couldn´t locate it – who knows the source?

Science of course and effective too

Most people in the field search Pubmed but there is another site that I frequently visit – the European patent database that often have more concise information. Look at current allergy patents – the last one will definitely work you may also use a big plastic bag ;-)

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Be aware that being cynical is probably bad for your heart.

déjà-vu

ZEIT online has an interesting article about ddéjà-vu – a rare syndrome. Some psychiatrists believe that déjà-vu episodes are the result of a faulty memory that brings up a similar episode. Others believe that there is nothing at all – just electric loops of a petite mals that can also be triggered by electric stimulation of the gyrus parahippocampus. ZEIT online also cites a study of Alan Brown that adds evidence for some kind of implantable memory.
I have frequently déjà-vus when reading the scientific literature (sometimes I even believe in groundhog days). One of my teachers in Marburg always said that “study of the scientific literature prevents from new discoveries”. Yea, yea.

Serendipity

What is serendipity? Probably an artifical word used by Hugh Walpole 1754 in a letter he wrote to his friend Horace Mann

the effect by which one accidentally discovers something fortunate, especially while looking for something else entirely

Some examples www.scienceiq.com/Facts/

Ambroise Pare learned otherwise when, after running out of oil during the siege on Turin, he found his untreated soldiers recovering better than the treated ones. Another example is Louis Pasteur. He left a culture of chicken cholera microbes in his lab … Rontgen’s chance observation of a green glow in the corner of his laboratory led to the discovery of X-rays. … Finding a way to make rubber impervious to temperature changes became an obsession to Charles Goodyear. One day, in 1844, after countless unsuccessful trials, he dropped a mixture of rubber and sulfur on a hot stove. …Vulcanization was born…. Kekule proposed the cyclical structure of the benzene ring after dreaming.

Anf course the famous text by Arthur Kornberg, Stanford Medicine 1995 “Of serendipity and science” (that seems to vanished from the internet).

Photoshopped

How to recognize photoshopped pictures? This will be a routine task for future editorial process (BTW I already recognized a faked gel gel picture where the edges and density of the bands looked somewhat artifical). However, with the ever increasing technical capacities we probably need non-destroyable, watermarked pictures from professional scanning and digitizing equipment.
In the meantime, check Wikipedia and the links there. I believe that the majority of the faked pictures could have been detected by splitting up color channels and looking at non-continous transitions of hue (“Farbton”), saturation (“Sättigung”) and brightness (“Helligkeit”) or grey value. This will even work with scanned figures although I would recommed to check original computer files (that may always be electronically stamped by previous publishers). Don´t miss the website of the mp3 developers).

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Addendum

Here is another examples how to recognize photoshop spoof:

set the hue to a low setting, the saturation to a higher setting, and mess with the light and look for blotches of color that don’t follow the rest of the image

22-2-07: The JBC has now adopted an explicit policy

“No specific feature within an image may be enhanced, obscured, moved, removed, or introduced. The groupings of images from different parts of the same gel, or from different gels, fields or exposures must be made explicit by the arrangement of the figure (e.g. using dividing lines) and in the text of the figure legend. Adjustments of brightness, contrast, or color balance are acceptable if and as long as they do not obscure or eliminate any information present in the original. Nonlinear adjustments (e.g. changes to gamma settings) must be disclosed in the figure legend.

11-9-07 Hamin Farid has developed tools to detect digital tampering.

I require 1,000,000 dollars

Most scientists are urged to spend much of their time for getting research funds. Here is a another anecdote about Otto Warburg reported by Hans Krebs / p 57:

One day he [Warburg] asked the office of the Director-General [of Kaiser-Wilhelm-Gesellschaft, later Max Plack Society] to allocate 10,000 marks for his research. He was told that that the organization had no spare money; he should therefore write an application, which the Director-General would support, to the Notgemeinschaft (an emergency fund made available by the government for the promotion of research). Warburg replied that he had no secretary; the Director-General should put a secretary at his disposal. This was agreed. Warburg handed the secretary a sheet of paper and told her to type ‘Top left: Dr.Otto Warburg; top right: the date; underneath this: I require 10,000 (zehntausend) mark.’ This Warburg signed. The ‘application’ was succesful.

Yea, yea.

I swear by God that I will speak the pure truth

Will you state your full name?
Will you repeat this oath after me?
I swear by God, the Almighty and Omniscient, that I will speak the pure truth, and will withhold and add nothing.
You may sit down.

I have heard this sentence now eight times – on eight new CDs from the Nuremberg trials with original material by the American Record Group 238 “Die NS-Führung im Verhör” documented by Ulrich Lampen with an introduction by Peter Steinbach. The introductory remarks are well balanced, the sound quality excellent, translation and dubbing artists outstanding, but there seems to be no documentation in the CD box in particular for CD 7, the interrogation of Prof. Dr. med. Karl Gebhard.

I am giving therefore some links here – as otherwise you will not really understand what this man did. None of the other interviews recorded such an aggressive, rude and loud tone – a big-headed, omnipotent medical professor that still believes that winning of the war would have enobled his medical research.

www.shoa.de, the largest German portal on the Holocaust has an article about Herta Oberheuser that contains some information about Gebhard; more at German Wikipedia but the most detailed account may be found in Klee, Auschwitz pp 152. Gebhard was one of the few German physicians that were hanged after the war.

Born in 1897, he studied as Mengele here in Munich, habilitated 1935 as a scholar of Sauerbruch and became associate professor in Berlin. As of 1937, he held a chair of orthopedic surgery, became head physician at the sanatorium (Heilanstalt) Hohenlychen and “Oberster Kliniker beim Reichsarzt SS”. Ravensbrück was only a few kilometer from Hohenlychen. Klee has all the terrible details of his medical research: artificial infection with Clostridium, wood and glass implantation into the lower legs, explantation of limbs, trepanation with artifical brain injuries, phosphor burning of the perineum as punishment, consecutive murdering of patients with evipan or by shooting. Gebhard was medical attendant of Heinrich Himmler and president of the German Red Cross (sic!)

Protocols

The protocols are available as microfilms. I am currently checking with the editors if they can be copied to PDF format.

Mercy and truth

Doing science and seeking truth may be occasionally unkind to others. Watching a beautiful movie (“Babette’s Feast“, Oscar 1988) I was deeply moved by the speech of the officer Lorens Löwenhjelm about “Barmherzigkeit und Wahrheit” or “mercy and truth” – it goes back to

Ps 85:10 (KJ) Mercy and truth are met together; righteousness and peace have kissed each other.

Also Martin Luther found that remarkable as well as Wolfgang Huber. Yea, yea.