Is it the drug companies? Really?

Interesting article from Scientific American (which I viewed as a sacred text when I was you): how-drug-company-money-undermining-science.  Sort of an investigative journalism take on the ideas of conflict and research.  Easy to get excited about, but hardly news nor possibly the most pressing problem.  Lots of the activity of academic research in medicine is problematic.  Sure, for-profit interests funding 'independent' researchers on one hand and directly paying them on the other has literally changed the face of medical practice.  But the institutions themselves are bound up tightly, as well.  For every dollar that gets paid for research anywhere from $0.25 to $1.50 go to 'overhead,' meaning the institution itself. And as companies often pay higher overhead rates, there is plenty of graft to go around.  As this article suggests (but avoids investigating) the way in which money is dolled out by the government, the 'public' funding of research is hardly different.  The folks who control the 'advisory' boards are able to continue to feed funding to favored colleagues and projects.  Really innovation from unknown investigators is highly unlikely to be funded.  So the vast majority of research amounts to simply reproducing the existing paradigm.  This is despite hundreds of billions of dollars spend in cancer, for instance, that have produces few real, substantial changes at the clinical level. 

The culture of medical research isn't bad or good, it merely is unreasonable when evaluated against its stated aims.  And no one is in charge of it, there is no single 'source' nor accountable person, group, nor entity.  Change will come from the margins, as it always does.  That's why I like it out there.  Lonely, but almost unfettered. 

Paradigmatic mice

 In a fine article, researchers describe the optimal temperature for mice in nature and the way lower ambient temperatures common in research buildings alter their behavior (the mice have to eat about 30% more in order to generate the necessary body heat. Of course, the convenience of not working in a steam bath (mice apparently prefer 30 C - 86 F but become feisty when warm) for the lab staff probably effects the results of the experiments, unless the experiments are supposed to be done on cold mice.  Seems like a simple thing and the intervention is simple as well, just provide some material for the mice to build a nest.  So maybe folks will start, so they can have a better idea of how their interventions actually affect mice.  Maybe some failed drugs, for example, become viable again.  Oh, and a few viable ones end up 86'd.

Of course, that leaves us with the inverted time structure, meaning mice are noctural, but we wake them up during the day to do our work.  Even this article describes their lighting conditions to be 14/10 (light and dark).  Hmmm.  Single major regulator of every biological function is light.  What kind, how much and when.  So think of all the drugs that worked so well in mice (who were given those drugs mostly during the daylight hours, which is sleep time for mice) and not so well in humans (who were given them during the waking hours for humans).  The more central a practice is to reproducing the basic assumptions of the practitioners, the less likely it is to be changed, obviously.  And research science must first reproduce the assumptions and then it can proceed.  But only then.  Which is why we have had 50 years or more of incrementalism is science.  People even expect it "adding to the knowledge base."  Maybe it is time for a little creative destruction.  At least we'd have happier mice....


http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0032799

Paradigm, Paradigm, uber alles!

JAMA published a study looking at the effects of bone marrow derived stem cells on patients with heart failure.  Predictably, the study did not demonstrate significant benefits for the patients who actually received the stem cells as compared to the placebo group, which is not an uncommon outcome in these kinds of stem cell therapy trials.

From a scientific perspective, what is important is that the underlying (and unstated) paradigm is preserved.  In this case, as in virtually any other in this area, the putative stem cells are used precisely like a drug would be used, as a stand alone intervention.  Which is precisely the inverse of what in vivo tissue regeneration is.  And rather than the methodology, which is biologically unsound (well, it is really absurd, but if that is written folks get offended), is unshakeable, so the discussion degenerates to a mostly morally driven discussion about the 'value' of the autologous pluripotent bone marrow cells use here and the vaunted 'embryonic stem cell."   The value of virginal stem cells has significant appeal independent of efficacy and a constituency that has significant economic interest in their use, but 'parts is parts' as the story goes.  The elusive feature is the dangerous one as well.  The gruelingly childish, no, make that magical, idea that investigations in biology require careful manipulation of a single variable at a time is not supportable, not true and virtually impossible.  But aside from that, even if it were possible to operationalize, it is contrary to the basic of biological activity.  All biologic emerges within a recursively non-linear milieu and is wholly dependent upon that milieu for initial trajectory and outcomes.  Without concurrent nurturing (whatever that may mean) of the context, the milieu for stem cells, there is no plausible reason to expect any enduring efficacy.  But it's "Paradigm, paradigm, uber alles!" in the stem cell field for the foreseeable future, at least in the mainstream of medical research, however backwater it really is.