Tag Archives: History + Insights

All roads to NLM

This is not just an addendum to my previous post free-for-all or to number-cruncher: the 12 Dec NIH press release links to a new and exciting database

NIH Launches dbGaP, a Database of Genome Wide Association Studies
The National Library of Medicine (NLM), part of the National Institutes of Health (NIH), announces the introduction of dbGaP, a new database designed to archive and distribute data from genome wide association (GWA) studies. GWA studies explore the association between specific genes (genotype information) and observable traits, such as blood pressure and weight, or the presence or absence of a disease or condition (phenotype information).


29-5-07 dbGaP suffers from some broken links but content improves!


Christmas present – your digital book copy

Maybe you don´t want to wait until Google Scholar has it; maybe you are interested in a higher quality: Here is the web address digiwubu.gdz-cms.de at the Niedersächsische Staats- und Universitätsbibliothek Göttingen where I once studied theology.
There should be no problem to scan any book published before 1900, however you can ask also for books published later than that date. Costs will be are 0.25 € per page plus 5 € for handling and shipping a CD.
“Google Books Library Project” is currently scanning in Harvard, Stanford and Oxford >15 million volumes – German scan factories are in Göttingen and Munich. Yea, yea.

Exodus of science from Germany after 1933

A book that crossed my desk only very recently is about the exodus of science from Berlin after 1933. As a child I never understood the second commandment when God said to Mose that

Ex 20:4 I am a jealous God, punishing the children for the sin of the fathers to the third and fourth generation of those who hate me, but showing love to a thousand {generations} of those who love me and keep my commandments.

I always thought the idea to be unfair to be under collective guilt. Nevertheless when reading this book (published already in 1994 by Walter de Gruyter) we get a deeper meaning how science is affected for many generations by the displacement of the most prominent scientists.
Particular important in this book is the first chapter of Hubenstorf and Walther that highlights the situation in Berlin. Following world war I, Berlin had become the indisputable center of most scientific disciplines in the German speaking territory. In some disciplines Leipzig, Vienna or Munich may have been competitors, economics had been strong in Kiel, mathematics and physics in Göttingen, history in Marburg, however, for most scientists Berlin had been the highly desired “endpoint” of their career. he Friedrich-Wilhelms university had been the largest university, but there have been many more science organizations like Technical University Charlottenburg, Deutsche Hochschule für Politik, Preußische Akademie der Wissenschaften and Kaiser-Wilhelm-Gesellschaft (that is covered in more detail in another excellent chapter).
Medicine has been hit hardest during the Nazi period by having a large number of Jewish scientists. The resulting repercussions in the realm of science are described at different levels. Starting with a typology of transformation of scientific institutions, the establishment of new disciplines and the establishment of a military science sector, the autors give many historical details about the ways of scientific publishing or the organization of displaced scientists.
The cancer research department of the medical faculty fired 12 or 13 scientists; the hygiene institute dismissed 8 of 12 scientists including later Noble prize winner Erwin Chargaff. Hospital Lankwitz fired all physicians, Neukölln 67%, Freidrichshain 62% and Moabit 56%.
It is a terrible story – you can read how the editor of the Deutsche Medizinische Wochenschrift Paul Osswald Wolff was replaced by a Nazi supporter. Karger publisher even moved from Berlin to Basel (where they still reside today).
As any good science is strongly connected to teaching it may be understood that breaking this tradition has lead to a punishing of the children for the sin of the fathers to the third a fourth generation. Science politicians may even recognize the downside of spending money into science: they will be blessed by thousands of generations.


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

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:


100 years of allergy

Clemens von Pirquet (1874-1929) was the first to introduce “Allergie” into clinical medicine by characterizing an altered immune reaction of the body to foreign substances. The famous paper was published 1906 in the “Münchner Medizinische Wochenschrift (MMW)” Volume 53, page 1457-1458.

AB Kay published a nice essay on “100 years of Allergy: can von Pirquet’s word be rescued?” that includes an English translation of the above paper. The MMW has a contemporary obituary of Meinhard von Pfaundler (1872-1947) who was one of the earlier directors of the Münchner Haunersche Kinderspital.

Finally, the “Wiener Klinische Wochenschrift” has a CV of Clemens von Pirquet, showing his way to Baltimore and Breslau back to Vienna until his tragic end by committing suicide together with his mentally ill wife.


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.

Gene lists by automatic literature extraction

Just found at the HUM MOLGEN bulletin board a link to Fable, a new automated literature extraction system. Fable is pretty fast and can output gene lists. Sure, the screenshot below shows only those genes that I mentioned in the abstract, but this is not so bad as the most important genes wil be placed there.
BTW, the number of reviews on asthma genetics have been falling to less than 50% after closing the Asthma Gene Database. Maybe this new service will help to re-establish the former output of reviews ;-) yea, yea.


Science at work

I need to send back to the library my copy of the Altman book. It is a really excellent book, very informative and easy to read. Altman even does not stop at critical situations (page 12 of prologue) where he describes scientists as

Scientists are human. They have their jealousies. They gossip. They spread rumours. They exaggerate. Sometimes they treat hearsay as fact.

Me too, yea, yea.

IL4 cluster revisited

I am interested in 5q31 and the IL4 cluster since I met David Marsh in the lobby of a hotel in Heidelberg around 1993. David was one of the founding fathers of asthma genetics and I renember how he vividly told me that he has a forthcoming Science paper on the IL4 cluster and IgE. The cluster is still one of the best allergy regions where the signalling through IL4 and IL13 now gets more interest than the work of any of his competitors.
Nature genetics now has an update on the 3-dimensional resolution of the genomic region. It is not cristallographic work as might be expected but a nice study of the chromatin structure that is leading to a coordinated expression of these cytokines. SATB1 (special AT-rich sequence binding protein 1) is thought to anchor specialized sequences letting DNA loops come into interaction. I wonder if there might be even a direct physical interaction of the IL4 and IL13 promotor and if there will be any SNP influencing that interaction? David (who died of brain cancer in 1998) would have really liked this work. Yea, yea.


Hotel Dieu

The Hotel Dieu in Paris has been one of the first pediatric hospital in the world (see my photo of the hospital entrance). I recall from the detailed history of allergic diseases by Schadewaldt that at the beginning of the last century it was difficult to presen the students a case of the Bostock hayfever.
The disease was so rare that it took more than one week to find a child with the typical symptoms. Yea, yea.


Do you know …

…. why the language of the internet is English and not French? It is an interesting hypothesis that the yellow fever which decimated Napoleons troops in Santo Domingo was a crucial factor in the decision to sell Lousiana in 1803. Although German was also a science language around 1900, it certainly became discreted by two world wars. Yea. Yea.

Nice to know

-moblog- There are many things “nice to know” but only a few “need to know”. Molecular epidemiologists having access to large datasets sometimes forget what most people on earth “want to know” – how to prevent and cure human disease.

Born to be write

A decade ago Karen Hunter (at that time Senior Vice President of Elsevier) did a brilliant analysis why scientists publish:

For academic scientists, the research paradigm is the experiment and the publication output is a journal article. Academic science researchers publish to establish their claim at a specific time to a specific result. They publish to gain other forms of recognition (such as promotion and tenure) that require publication. They publish in order to have independent certification of the results and to have those certified (refereed) results archived in perpetuity. Finally, they publish to communicate with those who may be interested in their works today …

She continues with another important aspect

… not the circle of cognoscenti (who do not need publication to be informed) but researchers in related fields, researchers in less well-connected institutions and students working their way into the inner ring.

In my opinion, the “claim at a specific time to a specific result” is probably the most relevant motivation for a scientist. Nevertheless having claims on ideas presented in a printed paper seems to be still a habit of the pre 1995 stone age of scientific publishing. Databases will be certainly as reliable in the future as printed paper. I guess that in 50 years the access to current electronic documents will be even better than to any printed paper. Yea, yea.

On the “Self”

If I would ever find the time, I would write a book on the “self”. Inspired by the Eccles/Popper book that I bought as a student, I always wondered how different the self is being defined in sociology, psychology/psychiatry, philosophy and theology.
As my current focus is more on genetics and immunology, I found a paper by Francisco Borrego on the “missing self” quite interesting as it highlights the genetic self is determined mainly by MHC class I molecules, where only NK cells transfected with H-2Dd were able to confer resistance for being self-attacked. It would be nice if other disciplines could also provide such simple answers, yea, yea.


I have another suggestion: Zfp608 protects mouse mothers against immune-mediated attack by fetal cells.

Is there also a “digiself“?

Our identity has, for many years, existed quite independent of our physical incarnation in government, financial and other institutional databases. We are not real to the bank or other authorities unless we can produce something that links our physical self to our “real identity” in their database. We have many versions of this digital identity – or digiSelf, as I like to call it – spread among many databases, each with its unique characteristics, and inferred behaviours. Each one is more real to the institution – and ironically, to the people in that institution – than our physical self, what we consider to be our real self.

Genetics making up of Homo sapiens

Lets start a further workup of the evolutionary thread. With the complete human and chimp genome on our harddisks we are now able to compare genome sequence and genome activity of both species. A 2003 review by Sean Carroll summarizes our pre-genome knowledge about pan and homo lineages 6 Million years ago. The most interesting question is which mutations or genome rearrangements (Popesco 2006) are most relevant in the separation of lineages.

BTW I have still doubts about any positive effects of mutations (although this might be possible). Yes, I wonder also where are the exact pan-homo transitions (although the Sahelanthropus tchadensis might be a good candidate). Furthermore, I have doubts in survival of the fittest where non-survival of the non-fittest seem to be more relevant ;-) “Survival of the Sickest” is a CD of Mad Sin and a book of Sharon Moalem 2007.

Neuroanatomy might have provided some clues of a larger frontocortex in homo sapiens although the detailed cytoarchitecture could be as relevant. Noise of neutral substitutions could have confounded previous findings. It is also not clear to me if expansions and contractions of whole gene families are even more relevant. We may also renember that most quantitative traits have a polygenic background.

In any case FOXP2 could be associated with speech and language disorders (Vargha-Khadem 2005) where another prominent gene was now found in the 49 regions that are different between chimp and human but otherwise conserved (Pollard 2006). This new gene called “HAR1” is even expressed in the developing neocortex making it a prime candidate for species differentiation. Is there anybody able to convince me that the 18 fixed mutations in HAR1 have indeed a beneficial effect on brain development? A “leading edge” comment in Cell argues that all substitutions are upgrades from weak to strong base pairing:

Curiously, this weak-to-strong substitution bias in HAR1 extends over 1.2 kb, a region far larger than HAR1 itself. Such changes which also appear to characterize the HARs as a group undoubtely serve to strengthen RAN helices against dissociation…

I would also like to mention that male humans share more identity with male chimps than with female humans, at least on a genetic level, yea, yea.


Even blogs have a half-life of less than 1 week. A new PNAS paper by Michael Oldham shows a more integrated view of human brain evolution by examining gene coexpression networks in human and chimpanzee brains. This seems to be another promising approach.