Category Archives: Philosophy

Philosophy

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.

 

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Philosophy

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.

 

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Philosophy

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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Philosophy

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.

 

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Genetics, Philosophy

Curiouser and Curiouser

3 Comments

–Day 1 of Just Science Week–

… said Alice in the Wonderland. Curiouser an couriouser all these gene X – trait Y – value P – association studies that are so often not reproduced. Science magazine now publishes letters of 3 independent groups contributing 6 essentially negative studies. This does not come unexpected – maybe we should look again at the original paper?
The introduction seems to be somewhat misleading — obesity is not primarily associated with another disease but with over-eating — and a heritablity of 70% is hard to believe. BTW I wonder why neither the editors, reviewers, or authors noticed the editorial errors (page 281: the 1775 cases in the text appear as 1835 cases in table 3; table 3 itself is redundant and misses genotype counts as well as the 923 FHS individuals from page 280). However, that does not explain why the association cannot be reproduced by other groups. So what could be the reason that the initial results were not be replicated?
Looking more closely at the case-control definition it seems that obesity is defined in different ways in the different populations – the German sample by cutoff BMI>30, the Polish by 90th to 97th percentile, the Nurses’ trait is never explained and the Africans are split by quartiles. How would a consistently defined look across all these populations? There seems to be also no proof why SNP rs7566605 somewhere 10000 bases away from a gene should have any biological function. Just because it “is an attractive candidate gene … [as it] … inhibits the synthesis of fatty acid” ?
More general, I believe that it is not adequate to make any conclusions about causal interference from a statistical association alone. There are many known fallacies; reasons for non replication may be simple errors during phenotyping or genotyping, inadequate statistical power, a biased analysis, selective reporting, population stratification or population unique effects. My six criteria for a meaningful association are:

  1. sufficient strong association, stable in subgroups and in populations of the same ethnic background
  2. importance of the tagged mutation leading to regulatory or structural protein change while excluding any confounding LD effect
  3. functional importance of the resulting protein with the trait of interest
  4. known genetic background and interaction with other genes and proteins
  5. known time of onset of functional change and interaction with relevant pathway
  6. known interaction with the environment, possibly also in an animal model

Quite simple ;-), yea, yea.

 

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Philosophy

Are science blogs dangerous?

1 Comment

Amnesty International reports that an Egyptian blogger is now facing up to 10 years in prison for criticizing Egypt’s religious authorities. A German blogger writing about constructing buses in China even faced an invitation to a court in Bejing. And everybody knows of Ellen Simonetti becoming famous for being fired by Delta.
A major difference of blogs to accredited journalism is also the limited capacity to respond to any prosecution: I don’t have any money for a lawyer while newspapers and journals can hire dozens.
Sure, science blogs are much less intrusive but there is always a risk that the empire will strike back; 99% of grant and paper reviews are anonymous.
BUT, there are good news – the blog community is large and always alert. As a science blooger writing on bad science you can now even get nice prizes – gratulations to Ben. Don’t forget that all students arriving in your lab have read your weblog first.
Refraining from all activities also involves some risk, yea, yea.

 

CC-BY-NC Science Surf accessed 03.11.2025
Philosophy

Resilience

Yesterday I heard for the first time of this psychology term. It describes how humans cope with stress, anger or other negative events – even over long time periods. Some people give up but others still grow (“skipjacks”). Seems that this trait can be immedately tested in scientists ;-) there is even a journal Disaster.

 

CC-BY-NC Science Surf accessed 03.11.2025
Genetics, Philosophy

Enter without knocking if you can

2 Comments

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?

 

CC-BY-NC Science Surf accessed 03.11.2025
Allergy, Joke, Philosophy, Software

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.

 

CC-BY-NC Science Surf accessed 03.11.2025
Joke, Philosophy

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.

 

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Philosophy

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).

 

CC-BY-NC Science Surf accessed 03.11.2025
Philosophy, Software

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.

 

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Philosophy

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.

 

CC-BY-NC Science Surf accessed 03.11.2025
Philosophy

Tono-Bungay

No, this is not about H.G. Wells’ book, but about Paul Pearsall (who quotes Wells) and what he has to say about the ever increasing self-help-, Dr. Phil-, Dr. Laura- and Dr. Ruth- and whatsoever market The Last Self-Help Book You’ll Ever Need: Repress Your Anger, Think Negatively, Be a Good Blamer, and Throttle Your Inner Child.

Publisher Weekly says that he is

… arguing against the “platitudes of self-empowerment” that dominate the self-help bookshelves. Their relentlessly upbeat tone and unrealistic idea of happiness will only make you feel worse, he says. Using research studies to bolster his points … Dr. Phil. Pearsall, an adjunct clinical professor at the University of Hawaii at Manoa, wants readers to stop being so self-centered. It’s more important, he says, to love others before oneself, and appropriate guilt and anxiety are essential to learning to live a better life.

I enjoyed every sentence of this book, the inner pages fulfill what the title promises: A realistic approach that follows sound scientific principles.

 

CC-BY-NC Science Surf accessed 03.11.2025