Informed consent – what else?

Ian Chalmers pointed me to a paper on “Rethinking research ethics” by Rosamond Rhodes. She basically argues that protection of the vulnerabale (as a major rationale of informed consent) has been leading over the past decades to a “tangled web of research policies that are sometimes at cross-purposes with the goals that they should actually promote” with current research policies “too often limit research … and therefore promote practices that are unethical and unreasonable by being harmful, wasteful or both”. She tries to make this clear with footnote 9 “Parents should certainly protect their children. But, consider the bicycle riding policy that parents would adopt if they took protection to be their primary parental responsibility. Children would not be allowed to ride bicycles because it would subject them to risk of harm” and so on.
While I am always be willing to discuss dogmas, I think that current research policies on informed consent are well developed for many reasons. Voluntary consent in a democratic society is undispensable. Full information is also vital and not only a matter of protecting vulnerables but also of respect of autonomy. Self-determination leaves the proband the choice to participate e.g. sharing the investigators goals or not. Of course we should recognize when “informed consent” is perverted by just filling in another form. With a few exceptions there is no excuse for not having asked for full informed consent.
I am even shivering by her view “if the Nazi doctors’ only ethical failure in their treatment of human subjects involved lack of informed consent, their behaviour would have been no worse than that of their fellow scientists around the world”. Does she really want to affront scientist around the world? Or does she want to downplay the atrocities of the Nazis?
Coming back to her example – has she ever heard about bike helmets? It is my responsibility to minimize harm for the individual, while allowing movement forward. Yea, yea.

Analyzing the log files for this site, I found this page is retrieved frequently every day. Maybe I should expand on this topic?

{democracy:3}

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Pushing the limits of cytogenetic FISH

-moblog- HMG has an interesting paper of Fei Sun and Renee H. Martin – showing a first visable recombination map of the male human genome. They obtained testicular samples from 10 males where each contributed 100 pachytene-stage cells. Chromosomes were identified by blue CREST centromere coloring and yellow MHL1 coloring of crossing over sites. Unfortunately the paper is not so easy to read but they have excellent figures. On average there are 50 cross-overs per set (which is more than I expected). The total number goes down from 52 at age 30y to 46 at age 80y (which may explain the higher chance of aneuploidy at a higher age). Individual crossover frequencies look extremely variable, chromosomal locations are clustering at different site -see my recent blog on recombinogenic sequences. Activity at centromeres was always low while chromosome 21q showed a high individual variablity. Why was there never detailed workup of physical and linkage map? Nay, nay.


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Kernel function

Slashdot corbettw writes “This article on Yahoo Science News describes a new finding that explains how the thalamus is used by your brain to essentially boot your brain, and provide for central processing and control of all impulses going to and from the cortex. The article describes its function as an operating system, but from the description it actually seems closer to the functions of a kernel.” That’s true if we see a kernel as abstraction layers for hardware, especially for memory, processors and I/O that allows hardware and software to communicate. It is probably a monolithic kernel that executes all the code in the same address space. Nay, nay.


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Pacemaker

Have you ever heard of pacemaker? No, not about cardial pacemaker – I am talking about pacemaker at Marathon distance runs. They are usually carrying a flag showing the target time 3:00 h, 3:15 h, 3:30 h, 3:45 h and so on. Yes, of course also in science there are pacemaker at all levels, some have even flags without ever participating in a race. I have just read a nice book of Joachim Stall and Matthias Klumpp about “Running with music” that has a list of songs with beats per minute – surf to joggymeter. Yea, yea.


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Paper cemetry (is La Sombra del Viento)

-moblog- Probably inspired by reading Carlos Ruiz Zafon “La Sombra del Viento – Shadow of the Wind – Schatten des Windes” telling about a cemetry of books I wonder whether it would make sense to
have also a cemetry of rejected papers. Would that be useful to have an arXiv.org-like access to papers that will otherwise be forgotten? Yea, yea.


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Role of Faust

-moblog- Edge The Third Culture has a long portrait of Craig Venter: “… His enemies have nicknamed him Darth Venter and accused him of putting the future of biology in jeopardy … journalists have cast him in the role of Faust…” The Celera genome admired in the East Room of the White House had been a composite of 5 different people including Venters own DNA (read about DNA sources). He is now going to make his private DNA public as well as an autobiography. Is anybody interested in reading any of the two? Nay, nay.


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Allelic specific expression

This topic has fascinated me since I read the Pastinen paper from the Hudson group (with updates in Science and Hum Mol Gen; the field probably started with the Yan paper). We had even written a DFG grant application that was not funded.

ASE uses a rather simple principle where the allelic ratio of a heterocygous SNP within a RNA transcript is taken as a measure of gene expression from the different chromosomes (that are carrying either the one or the other SNP allele). A ratio of 0.5 indicates equal expression and becomes distorted if a gene on one chromosome is imprinted or silenced by another way. The ratio can be rather easily determined by MALDI-TOF genotyping of cDNA by pooling protocols. I wonder why this hasn´t been more used as it is probably a more precise measurement than the artificially “self-normalized” expression ratios in classical gene-expression profiling (as Fan pointed out recently).

ASE seems to be much more common than I thought: 53% of all genes showed allele expression differences in at least one individual. Having such a screening instrument at hand, it could even help to clear our SNP genotyping lists. Yea, yea.


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Another difference between men and women

Aside from sex hormones, circulating vitamin D – calcidiol – serum levels show a consistent difference between men and women. Ok – I know that

  1. nuclear receptors are hormone-dependent transcription factors (Drané P, Mol Cell 2004; 16:187)
  2. 25-OH-D3 hydroxylase is upregulated by estradiol-17 (forgot reference)
  3. endometrium expresses VDR during cycling (Vigano, J Mol Endo 2006; 36:415)

but what is really responsible for this difference? A new Cell paper now shows that tamoxifen (an estrogen receptor antagonist) disrupts calcium homeostasis in yeast. Yea, yea.


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99%

Don´t read this if you haven´t finished your thesis.

Tadataka Yamada -former chairman of research and development for SmithKline Beecham Pharamaceuticals- is quoted in The Lancet of August 12, 2006, that “99% of what we do in industry fails”.

John Ioannides revises his PLOS statement from “most” research finding is false to “up to 90%” for a moderate risk factors with limited replication. Given the fact that many negative studies are never published, also academia would be in the Yamada range.

I should have been taught that earlier. Yea, yea.


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Geneticists and NBIA-PKAN

Geneticists continue to publish about “Hallervorden-Spatz” or “former Hallervorden-Spatz” syndrome.

The German NBIA patient group advocates for many years that these names should be abandoned (the American patient group even formally changed its name 2003). NBIA is a rare inherited neurological movement disorder characterized by the progressive degeneration of the nervous system; NBIA means “neurodegeneration with brain iron accumulation”. Another frequently used disease synonym is pantothenate kinase-associated neurodegeneration (PKAN).

The clinical syndrome has been described by the neurologist Julius Hallervorden and the neuropathologist Hugo Spatz. Robert Jay Lifton does not h>ave any material about Hallervorden and Spatz in “The Nazi Doctors: Medical Killing and the Psychology of Genocide but Ernst Klee in “Auschwitz, die NS-Medizin und ihre Opfer” and Benno Müller-Hill in “Murderous science” mentions both. Professor Hugo Spatz (1888-1969) was docent in Munich 1923, director of Kaiser-Wilhelm-Institut Berlin 1937-1945 and director of Max-Planck-Institut für Hirnforschung Gießen 1948-1957. Professor Julius Hallervorden (1882-1965) was department head at Kaiser-Wilhelm-Institut Berlin 1938-1945 and at MPI for Brain Research from 1948 on.

The former director of Max-Planck association Professor Hubertus Markl mentioned their involvement in Nazi euthanasia in his lecture on Oct 14, 2000 at MDC in Berlin-Buch (own translation): “Recent research showed that brains of hundreds of euthasia victims killed between 1939 and 1944 in Brandenburg-Görden, were mis-used for research purposes. In a single case Julius Hallervorden was present in person, while children were killed in Görden and brains consecutively analysed in his laboratory… As a biologist it remains for me to declare that this is an eternal dishonor for German bioscience.”


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The sib similiarity problem

We have done affected sib pair studies for many years with moderate success as we already described five years ago. Professor John Edwards brought to my attention the “sib similiarity problem“, that is still not widely known. ASP studies are based on “the premise that a set of ASPs will share more than the expected proportion of alleles at a disease-susceptibility locus with the implication that these were the sole cause for excess sharing”. This is not necessarily true and may be one reason of the failure of ASP studies. More or less by chance, I found that that the observation of 1 discordant sib in ASP families be an extremely powerful. “Being sane in an insane world” e.g. being healthy while having most of the risk alleles and all the environment risk that made the sibs ill. Yea, yea.


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Who is who in German genetic research?

You may want to start with names listed at Laborjournal. Aside from universities major institutes are with Max Planck and Helmholtz. Main funding comes by DFG (Deutsche Forschungsgemeinschaft, who lists all their projects at GEPRIS) and by BMBF (German Ministry of Research) with a few projects online at National Genome Research Network.


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