In 2011 a new cancer drug was approved, Provenge, from Dendreon Corp.  And I blogged about it then.  First of its kind, blah, blah, blah.  Short answer, about 4 months longer survival, which I do not oppose.  And it is $93,000.  But I already covered that.  This is about the business side of that equation.  The company just tok a header on an announcement of slower that anticipated growth:

"Chris Raymond, an analyst with Robert W. Baird & Co, who rates the company “Neutral” with a price target of $14, said he was unimpressed with the latest disclosure, and that it’s a sign Dendreon needs to do a better job of persuading its current base of physician customers to start prescribing the drug more avidly. “For us to get more constructive on the stock, we would need to see tangible evidence of an inflection point in Provenge account penetration,” he wrote"(Xconomy)

My interest is in the way in which the analyst identifies the 'problem' and the solution.  Dendreon has to do a better job of talking MDs into prescribing their drug.  Hmmmm.  Why would that be?  If the drug is so effective at improving outcomes, then what is the hesitation?  Could it be the model, where oncologist think about drug sales to patients as a principle profit center?  Or that the side-effects + benefits/costs is not as attractive to anyone as purported?  The state of oncology today is the incremental extension of a life at the very terminal end.  Pharmaceutical involution continues. 

I do work for a variety of companies outside of my usual work, all involved in some way in therapeutics or nutrition, or the like.  In general, much of what these non-medical companies are doing is developing regimen's of 'discipline,' whether it be ingest something, wear something and/or do something, that have an underlying commonality that is unspoken.  All of these kinds of 'clothes' are cut from fabric laid out thousands of years ago.  At least the Greeks had fairly elaborate criteria and mechanisms for self-discipline that rest (and still do) on a tautology of sorts.  The Romans continued these 'arts' and elevated them, and the practitioners.  The basic presumption is that men should resist that which is natural, but animal like, in order to achieve a higher human existence.  And the 'governing" of the self was the same degree to which a man could be fit to govern a wife, a family, a business, and ultimately empires.  Those who were fit to govern would be recognized by their ability to govern their own natural urges.  I understand the impulse to discipline here, the notion of creating order from chaos (and I do also understand the order in chaos...), but there aren't any data that support this.  Lots of crappy leaders were  likely regimented and loads of dynamic, effective leaders are personal train wrecks.  For those who don't get to (or won't, you undisciplined lot) read Foucault's 3 volume History of Sexuality, the wonderful observations he conveys are subtitles for the political theater of our day (and sad as it is).  The game is played out around these ancient ideas of discipline, at least until the unfit are weeded out.  Of course, they are only unfit on the grounds of self-discipline, and specifically self-discipline in sexual affairs, with damaging, but not fatal, chinks for ethnic, financial and social affairs.  But the dismissal of potentially outstanding leaders due to thousand year old imperatives is probably not a very intelligent algorithm.  But it is one that has infiltrated much of our sense of excellence.  Maybe we can just start to look for excellence itself?  Maybe that would be a better indicator of potential?  Just an idea...

Don't let the facts stand in the way of a good story...

The graphic (thanks Nature) is a linear representation of a way to think about how tumors develop blood supplies.  It is, of course, not actually what happens, but a way of thinking.  And that way of thinking has produced lots of attempts at intervention.  Of course, the interventions are not just applied to thinking, but to bodies.  And therein lies the trouble.  Recent work (http://www.sciencedirect.com/science/article/pii/S1535610811004478) has demonstrated what was likely a fairly obvious outcome.  Very popular (meaning blockbuster) anti-angiogenic drugs have been demonstrated to slow tumor progressions.  But hypoxia (lack of oxygen) is a primary driver in cancers becoming metastatic.  So primary tumors may not grow as swiftly, but metastatic tumors appear more frequently.  Of course, that was not part of the thinking.  But again, this is a real system, a complex biological web, not a thought experiment.

I remember the almost fever pitch of effort promoting Judah Folkman (pioneer of anti-angiogenic therapy) in a poorly disguised effort to deliver a Nobel Prize to him before he died.  It generated a simple, fatally-flawed logic of how to treat cancers by denying blood supply.  So we have another of the common, killer beliefs about medicine and science.  Killer, sadly.

It is a great company, trying to great things.  And has done some, from the standard model.  But when Geron announced that they were closing their embryonic stem cell efforts, it was like a lead weight falling on all the hopes of the embryonic promoters.  Geron had persevered where others had failed and got the FDA to approve an embryonic stem cell clinical trial.  As many know, they stopped that trial and closed down the whole division.  Startling to many (especially shareholders).  But the inevitable outcome for efforts that are born of a defiance to the facts of basic biology.  The facts are that the human body, given the right conditions, will rebuild itself.  

For the bulk of modern medical thinking, the adult body was "terminally differentiated," meaning it was a finished product and unrenewable, except for some few exceptions, the liver and bone marrow.  That's one reason bone marrow transplants have been done for 40+ years.  But what was a bone marrow transplant, but a kind of stem cell transplant, with blood stem cells.  And yet, our collective unconscious in medicine remained derived from what we can only think of as a long-standing view of the 'body' as a complete entity, a finished product that then slowly wore out.  As folks have found, bodies do regenerate, although inefficiently.  Think of how an injured brain 'rewires' itself, essentially 'regrowing' the kinds of connections that lead to function.  A transplanted female heart, in a male body, will become partly "male" with male heart cells (cardiomyoctes).  Where did they come from?  And a woman who gives birth to a boy, expecially if she has a sick heart, will find that some of her heart muscle is colonized with her son's stem cells.  The latter has greater relevance about what it is to be an "individual," not just about stem cells.

So, as the real stem cell business, using your own stem cells to cure disease, begins to gain momentum, we may find many of the unspoken presumptions of an old way of understanding bodies will fall away in the face of facts.  But do not look for it to go gladly.  We still hold ourselves above and outside of biology and the natural world.  But underneath it all, we are dynamic, renewable organisms, despite our unwillingness to do that.  Someday, maybe, we will stop fighting nature, supporting the myth of domination.  And then, maybe, we can learn the beauty of living within that nature, and within ourselves.

I was part of a meeting with a handful of noted cardiologist researchers discussing the development of a clinical trial using a medical technology to reduce pain from and incidence of angina.  We have already run a pilot trial that should very good outcomes for treated patients.  The strongest opinions of the group were that the endpoints of the study should be on angina frequency and exercise capacity, as that is the only thing FDA accepts as valid outcomes.  Lots of discussion about how debilitating the condition can be and how there are not good alternatives for folks failing medical management (love that, 'patients failing.'  In my world, medicine is failing the patients, not the inverse - yes, inverse).  Within our technology company, we have always been enamored of imaging, so originally divined to get some kind of imaging for the trials, but that was deemed both unnecessary and potentially pointless, as the images are highly variable, even among symptomatic patients.  A late-arriving cardiologist/researcher, quite young, gave an animated, even slightly angry, defense of images.  Of course, she is an imaging specialist, so did have a dog in the fight, so to speak.  Her argument met the harshest of academic fates, it was simply ignored and the meeting adjourned shortly thereafter.  While we got organized for dinner, she spoke to me under her breath, while looking sharply at the others, "There has to be an objective measure of change, you can't just rely on patient reports, they are just subjective."  I did not push her on this, as I might otherwise (like invoke Roshaman), simply because I wasn't sure she wouldn't get really upset, even as we went to dinner.  I thought about the two 'camps' in this clinical debate.  The older, seasoned clinician researchers were happy to rely on patient reports, because, after all, that is what constitutes the disease itself, is the patient complaint.  The
young researcher seeking objectivity as some kind of 'truth,'
can do so as long as she doesn't examine things too closely.
She might end up making the argument that patients should
be treated on the basis of 'objective' data, independent of
complaints.  That is the basis of lots of therapies, and lots
of unnecessary treatment and side-effects.  But more
interesting is this notion of 'objectivity,' in that even in
mathematics we find, at the core, a subjectivity that cannot
be resolved.  For example, the law of trichotomy lets me
state that any number is odd or even or zero.  Seems pretty
straight-forward.  So is Pi even or odd, as it is clearly not zero? Guess we have to take it on faith that it is one or the other. 

I know that I just wrote a bit about the goofiness of psychiatry, but I just can't leave it alone.  Hmmm...maybe I'd qualify for an obsessive-compulsive disorder there...So read this neat piece, but don't let one see you and definitely don't start laughing to yourself (at least in public).   My new favorite disorder is post-traumatic bitterness disorder (PTED), and a nice piece about it here.

It is kind of a microcosm of all politics.  There are lots of special interest 'disorder' groups, all vying for inclusion.  And the treatments are usually all the same (some medication if you are a psychiatrist or cognitive behavioral therapy (CBT) if you are not.   So here they all are, vying for space.  Hope they all get some.  Oh, and I think that PTED is the weltanshauung of New Englanders.  Since when did people start thinking is was abnormal? 

Vote for my disease....

I think that folks know I am a big fan of psychiatry, having worked in it and studied it for 25 years now, on and off.  I still think Nietzsche's definition is most apt, "Psychology was born of idleness."  Especially in that we understand to day that the mind/personality/your noun here is an apparition of the concatenation of  the nonlinear activity in the biological substrate (which I pointedly would not reduce to the 'brain' nor, in fact, to the individual, but more on that later).  So the LA Times ran this great article about upper middle class white folk who want to medicalize their children's behavior (and note, I did not call it 'bad' behavior...it is contrary to the parents' desires, but may be fully warranted as a measure of resistance).

What we have here is the usual kind of 'evolution' in psychiatry and psychology.  More and more non-conformist behavior becomes pathological, which means treatable, which means billable.   Think of it as medicating puppies for urinating in the house. Lots of incentive, but virtually no real need.  That is the prescription psychiatry has followed since the introduction of pharmacological interventions.  It is also why they are on the lowest rung of the medical hierarchy. But back to the point.  The point is that psychiatric 'disorders' are decided by a vote.  Folks vote new ones in and old ones out.  I'm personally pulling for 'disruptive mood dysregulation disorder,'  in that the phenomenal inanity of it is majestic.  But, more importantly and more interestingly, I am pulling for Cecelia.  Keep kicking, kid.  Eventually the adults will go away....