Category Archives: Philosophy

Curiouser and Curiouser

5.02.2007 admin 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:

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

Quite simple ;-), yea, yea.

Philosophy

Are science blogs dangerous?

2.02.2007 admin 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.

Philosophy

Resilience

30.01.2007 admin

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.

Genetics, Philosophy

Enter without knocking if you can

29.01.2007 admin 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 couldnÂ´t locate it – who knows the source?

Allergy, Joke, Philosophy, Software

Science of course and effective too

29.01.2007 admin

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 ;-)

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

Joke, Philosophy

déjà-vu

17.01.2007 admin

ZEIT online has an interesting article about ddéjà-vu – a rare syndrome. Some psychiatrists believe that déjÃ -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.

Philosophy

Serendipity

15.01.2007 admin

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).

Philosophy, Software

Photoshopped

14.01.2007 admin

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). DonÂ´t miss the website of the mp3 developers).

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 donâ€™t follow the rest of the image

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

â€œNo 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.

Philosophy

I require 1,000,000 dollars

11.01.2007 admin

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.

Philosophy

Tono-Bungay

9.01.2007 admin

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.

Joke, Philosophy

Do what you will this life’s a fiction and is made up of contradiction

7.01.2007 admin

If you also like William Blake’s poetry you might be interested in more quotes that have a true scientific background.

Philosophy

I swear by God that I will speak the pure truth

6.01.2007 admin

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.

Philosophy

Epidemiology in a fascist system

6.01.2007 admin

Götz Aly and Karl Heinz Roth show in their book that the German Nazi system would not have worked without counting people, identification, classification, separation and elimination. It is a detailed historical account on technical details of coding and storing information about the population, the census of 1933 and 1939, the infamy of telling people that their data of Jewish ancestry in a separate questionnaire would be treated anonymously (p 93). The 1939 census required a “supplemental card” in addition to the household card (p 32)

This card developed by security service, police as well as statistical office was used by the authorities to ask for individual descend (“Was one of you grandparent Jew?”) as well as for the education in commission of the military services. The card should be given back in a separate, closed envelope. The envelope – together with the official affirmation – should delude potential victims and let them believe by the fictitious anonymity to make absolutely true information which was indeed facilitated and guaranteed.

The supplemental cards were then used to build the “Reichskartei der Juden und jüdischen Mischlingen” – the basis of the Holocaust. The Holocaust started with a knitting needle – the tool to lift the punched supplemental cards.

As mentioned earlier, I think there is a particular obligation with population based studies in Germany where it took 40 years to build epidemiology from scratch again. This is a must-read book for every epidemiologist.

A few hours before being executed, Eichmann was asked by Mr. Ofer, the director of the prison (in my translation)

“What should the Jews have done? How could they have resisted according to your opinion? Eichmann: Disappear, disappear. Our most sensitive point, that they would disappear before being registered and concentrated. Our command units were too weak and even when the police of the respective countries supported us with all their strength, [the Jewish] had a at least a chance of 50 : 50. A mass escape would have been a disaster for us.

Philosophy, Theology

Mercy and truth

5.01.2007 admin

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.

Joke, Philosophy

Celebrities on science

4.01.2007 admin

BBC reports about celebrities speaking on scientific issues – and comments by experts. I would like another BBC news feature about scientists speaking on scientific issues from different disciplines, for example famous molecular biologists about ethics.