Category Archives: Philosophy

3 Rs

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.

Open peer review failed

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.

He can run slowly

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?

Quod licet Jovi not licet Bovi

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.

Philosophy, the voice of rationality in the dialogue with biological sciences (podcast)

Last week I attended a meeting in Neuherberg about the future of science and ethics in medicine and biology. Prof. Jürgen Mittelstraß (Konstanz) gave the introductory lecture, Prof. Herwig Hulpke, Prof. Friedrich Wilhelm Graf and Prof. Klaus Peter participated in the discussion moderated by Fraua Ferlemann (BR). The lecture by Prof. Mittelstraß was remarkable, I am offering here a 60 MINUTE PODCAST [in German only] while the manuscript will follow later in January 2007. Please let me know if you want the full audio records of the 2 hour meeting.

Prof. Mittelstraß (left) and Prof. Graf (right) during the discussion
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Human breeding

There have been always attempts to make humans better – an idea that attracted people nearly every century. Ovid created Galatea from a statue, Goethe’s homunculus originated from a test tube, Mary Shelly created her monster from corpses, Bulgakows proletarian derived from a dog and Sloterdijks Menschenzüchtung by a fancy idea. There is only a minor difference at the end of 2006 – technical possibilities of genetic testing and genetic engineering are much higher developed. Yea, yea.

Open culture podcasts

As a frequent traveller I like podcasts. Here is a quick link to Open culture that have a huge university podcast collection including many foreign language selections (Boston College, Bowdoin College, Collège de France, Duke University Law School, Harvard University, Haverford College – Classic Texts, Johns Hopkins, Northwestern University, Ohio State, Princeton University, Stanford University, Swathmore College, University of California (the best collection), The University of Chicago, The University of Glasgow, The University of Pennsylvania, The University of Virginia, The University of Wisconsin-Madison, Vanderbilt University, Yale University and Ecole normale supérieure). If you don´t like proprietary formats you need to find the good and the bad apples.

Dr. med. Sigmund Rascher, KL Dachau

On my way to work I am crossing every morning in Dachau East the former Nazi concentration camp/Konzentrationslager (KL). Its a monument of inhumanity and the deepest point in the history of “science”. A large number of prisoners were abused by SS doctors for medical experiments; an unknown number of prisoners suffered agonizing deaths in the course of atmospheric pressure, hypothermia, malaria and other experiments.

photo by 11 Dec 06
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Having a longstanding interest in history (and even published on the 50th anniversary of the Nuremberg trials) I have now been very interested in a new book by Sigfried Bär, one of the outstanding German science writers “Der Untergang des Hauses Rascher”, a history of the life of Dr. Sigmund Rascher, anthroposophic scholar, medical student, DFG-scholar, minion of of Heinrich Himmlers, air pressure and hypothermia researcher at KL Dachau and finally prisoner who died by being shot in the neck.

Dr. Bär spent several years researching the life of this mass murderer. He contacted relatives of Rascher, looked at family photos, talked to people who knew Rascher and went to archives. This is a unique document showing the avidity of a researcher for recognition by scientific colleagues. Other books from my own library that I recommend:

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The mind has a thousand eyes

The night has a thousand eyes,
And the day but one:
Yet the light of the bright world dies
With the dying sun.

The mind has a thousand eyes,
And the heart but one.
Yet the light of a whole life dies
When love is done.

Francis William Bourdillon

(found 7/12/06 on the inside cover of an old book with title “Perdita” in the patient library of a university clinic)

Assets minus debts

Slashdot reports a United Nations study that

the richest 2% of adults in the world own more than half of all household wealth… Most previous studies of economic disparity have looked at income, whereas this one looks at wealth – assets minus debts.

Looks similar to science budgets, yea, yea.

Addendum

An interview with Richard Münch in Laborjournal 12/2006, p.23 confirms this: 17 out of 100 German universities consume 50% of all funds provided by DFG. He furthermore believes that SFBs and research networks are a kind of ideological framework; projects are not assessed retrospectively; there is an overkill of management costs where a considerable part of third-party funding is used to get more third-party funding.

Tit-for-tat or altruism in science

No, this essay will not deal with altruism in science but with the science of altruism. There are two new papers from the Fehr group (one in Science on Nov, 3 about diminished reciprocal fairness after magnetic stimulation of the right prefrontal cortex and a second in Nature on Aug, 24 about altruism in two indigenous groups in Papua New Guinea). I was, however, much more impressed by their recent review of human altruism.
Cooperation between genetically unrelated groups is a typical human behaviour (otherwise seen only in ants, bees and the naked mole rat) where there seems a strong reciprocity between selfishness and altruism. Cooperation is rarely stable and may deteriorate under worse conditions. Altruistic rewarding and reputation seeking seem to be the most powerful determinants of future donors’ behaviour where effects of punishing behaviour seem to be underestimated: Cooperation in larger group continues only if punishment of defectors and non-punishers is possible.

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Prevention of fraud

Donald Kennedy is writing in this week’ Science editorial about Responding to Fraud. The editorial is even more about prevention of fraud: The external reviewers ask for future risk assessment of potential fraud. Science will think in the future

… which papers deserve particularly careful editorial scrutiny. Papers that are of substantial public interest, present results that are unexpected and/or counterintuitive, or touch on areas of high political controversy may fall into this category…

I appreciate such an initiative and I agree that science is based on an assumption of trust – no procedure will be immune to deliberate fraud. However, looking both at people and at papers could be worthwile. I would give extra score points for

  • too ambitious institutional environments
  • large and anonymous organizations
  • poor social and scientific interaction at a local level
  • limited scientific qualification or background of researchers or department heads
  • time pressure, too many projects, no longterm goals
  • direct financial compensation in return of scientific impact
  • past history of minor misconduct

Looking at papers will also reveal inconsistencies

  • contradictory numbers
  • suspicious modifications of figures
  • original data not public available
  • original documentation not public available
  • constructs, cell lines, animals not public available
  • inadequate point by point response to review
  • insufficient documentation of IRB and authorship

Another option is to pay reviewers – the review process is becoming more and more time consuming – and even to plan on-site evaluation. An option probably not feasible is to delay publication until the main findings are independently reproduced.

Finally, I see a large gap between the attempts of Science and Nature to improve their performance while some average impact journals never respond if you ask them to correct or withdraw a highly distorted paper. Yea, yea.

Addendum

Guide to promoting integrity in scientific journals published by the Council of Science Editors

I agree with everything you said

“I agree with everything you said that was correct, and I disagree with everything you said, that was incorrect” (Adlai Stevenson according to AJRCM 2006;174:1056) – a nice comment that fits every situation.
The German Spiegel has an interview with Tim O’Reilly about the quality of internet resources. It seems that everybody can voice his or her opinion while the final decision about a feature or a patch is done in the “inner circle”. Entry to the inner circle is limited to those who qualify by previous contributions – probably a very similar system in science. O’Reilly talks in this interview also about Jaron Larnier’s warning that Wikipedia may be dangerous for creating mono-culture-knowledge. He agrees that Wikipedia has been abused in the past but believes that the mechanisms behind Wikipedia to identify abuse are much better than in any political system, yea, yea.

Zeitgeist

It seems that the German word Zeitgeist is increasingly used also in English texts. When thinking again and again about science and scientists, I always come back to a famous assay of Karl Jaspers written in 1932 (he lost his professorship in Heidelberg 1937; in 1938 he was forbidden to publish any more).

The title of the essay is “Die geistige Situation der Zeit”. The chapter “Wissenschaft” is always a comfort to me when being desperate about the inequity of the scientific world. Here is an excerpt:

Wissenschaften leisten auch heute Außerordentliches. Die
exakten Naturwissenschaften haben einen aufregenden Gang
rapider Fortschritte in Grundgedanken und empirischen Ergebnissen
begonnen. Ein über die Welt verbreiteter Kreis der
Forscher steht in den Beziehungen des rationalen Sichverstehens.
Einer wirft dem anderen den Ball zu. Dieser Vorgang
findet Widerhall in der Masse durch die Handgreiflichkeit der
Resultate. Das sachnahe Sehen in den Geisteswissenschaften
hat sich zu mikroskopischer Feinheit gesteigert. Ein nie dagewesener
Reichtum an Dokumenten und Monumenten ist vor
Augen gebracht. Kritische Sicherheit ist erreicht.

Die Krise der Wissenschaften besteht also nicht eigentlich
in den Grenzen ihres Könnens, sondern im Bewußtsein ihres
Sinns. Mit dem Zerfall eines Ganzen ist nun die Unermeßlichkeit
des Wißbaren der Frage unterstellt, ob es des Wissens wert
sei. Wo das Wissen ohne das Ganze einer Weltanschauung nur
noch richtig ist, wird es allenfalls nach seiner technischen
Brauchbarkeit geschätzt. Es versinkt in die Endlosigkeit dessen,
was eigentlich niemanden angeht.

Nicht also schon die immanente Entwicklung der Wissenschaften
macht die Krise zureichend begreiflich, sondern erst
der Mensch, auf den die wissenschaftliche Situation trifft. Nicht
Wissenschaft für sich, sondern er selbst in ihr ist in einer Krise.
Der historisch-soziologische Grund dieser Krise liegt im
Massendasein, Die Tatsache der Verwandlung der freien Forschung
Einzelner in den Betrieb der Wissenschaft hat zur Folge,
daß jedermann sich mitzuwirken für befähigt hält, wenn er nur
Verstand hat und fleißig ist. Es kommt ein wissenschaftliches
Plebejertum auf; man macht leere Analogiearbeiten, um sich
als Forscher auszuweisen, macht beliebige Feststellungen, Zählungen,
Beschreibungen und gibt sie für empirische Wissenschaft
aus. Die Endlosigkeit eingenommener Standpunkte, so
daß man in häufiger werdenden Fällen sich nicht mehr versteht,
ist allein die Folge davon, daß ein jeder unverantwortlich
seine Meinung zu sagen wagt, die er sich erquält, um auch
etwas zu bedeuten. Man hat die Unverfrorenheit, „nur zur
Diskussion zu stellen” was einem grade einfällt. Die Unmenge
gedruckter Rationalität wird in manchen Gebieten schließlich
zur Schaustellung des chaotischen Durcheinanderströmens der
nicht mehr eigentlich verstandenen Reste früher einmal lebendigen
Denkens in den Köpfen der Massenmenschen. Wenn so
Wissenschaft Funktion von Tausenden als jeweils zum Fach
als Beruf gehörender Interessenten wird, dann kann wegen
der Eigenschaften des Durchschnitts auch der Sinn von Forschung
… durcheinander geraten.