The Rx Pipeline – Has The Spigot Been Turned Off?

A recent article in the New York Times by Cornell psychiatrist Richard Friedman lamented the fact that there isn’t much in the FDA pipeline regarding the development of novel drugs for mental health use. In his op-ed, Friedman blamed Big Pharma for a “crisis in drug innovation.”

Case in point: last year, the FDA’s Center for Drug Evaluation and Research approved almost forty new molecular entities (NMEs) – the highest number of such applications in more than a decade. Given the green light were agents for some exceedingly rare diseases, malignancies of all sorts, and cardiovascular pathologies. Yet with the arguable exception of Amyvid, Abbott’s new compound for the imaging of β-amyloid plaques in the brain (Alzheimer’s), none of these NMEs have known or intended psychiatric application.

[I say ‘known or intended’ since over the years many psych meds have been discovered serendipitously, though I hate for my profession to depend solely on serendipity for its advances]

There has been a recent spate of clinical trials in which potentially novel antidepressant and antipsychotic agents failed to show efficacy greater than that of placebo – sometimes as late as Stage III in development – and Big Pharma is suspected of having concluded that psychiatric drugs are just too uncertain and too risky to pursue. That’s not to mention also too expensive: estimates range to almost $2B, and up to 15 years, to develop and market a new drug. Glaxo Smith Kline has accordingly shuttered its psychiatric labs altogether. And as of this writing, both AstraZeneca and Pfizer have markedly scaled back their investments in CNS R&D.

Granted, psychiatric disorders can be chronic, recurrent, likely multi-factorial in etiology, and complex beyond our current comprehension of neuroanatomy and neuropathology. And while I personally do not support such testing, for better or worse, there is a dearth of animal models with the requisite validity to predict eventual human clinical outcomes. That being said, it is still sobering that almost all of the current psychotropics being prescribed in the United States share the same molecular targets in the brain as did their ‘primitive’ precursors from the 1950s and 1960s.

What we’re seeing in lieu of meaningful advances is a rush of what psychiatrist Daniel Carlat has labeled ‘Me Too’ drugs, those with nearly identical molecular structures and proposed mechanisms of action very similar to agents already on the market; there’s no new ground being broken thusly. And then there are the rebrandings of earlier drugs: approved antidepressants and antipsychotics attempting to win ‘official’ FDA indication for other conditions – anxiety, bipolar mania, refractory depression, chronic pain – despite the fact that off-label prescribing is already permitted and widespread.

All is not entirely dismal, though. Ketamine, a widely-prescribed anesthetic, has been shown to have powerful antidepressant effects (there’s that ‘serendipity’ thing again). And we now have a more thorough grasp of the pathophysiologies of certain CNS disorders, opening doors for further industry and academic research and collaboration. These conditions include those of the addiction spectrum, Fragile X Syndrome, pain states, and insomnia to name only a few.

Of course, this also raises the issues of intellectual property rights and patent protection, the subjects of future posts.

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Anubis and the Art of the Pick-Up

In his opus Antiquities of the Jews, historian Flavius Josephus documented that it was in this month in the year 19 C.E. that a dishonest slave and two wicked priests of the Cult of Isis were crucified on orders of the Roman Emperor Tiberius.

There were many reasons that this cult and related others were persecuted (along with the Christians of the era), not the least reason being that Isis and her cohorts were perceived as ‘eastern’ and ‘foreign,’ associated with the vanquished and only recently demised Queen Cleopatra. Perhaps the following story, then, was merely a contemporaneous cover for what was, in actuality, a crackdown on those viewed as subversive libertines whom the authorities had come to fear and loathe.

Per Josephus, there was a wealthy Roman woman of the day named Paulina. She was married to one Saturninus, and was said to have been “of a beautiful countenance… and great modesty.” And unfortunately a devoted follower of Isis and all the rest of the Egyptian pantheon. A fellow Roman aristocrat, Decius Mundus, fell madly in lust with Paulina and attempted to seduce her with words and gifts, all to no avail. The final straw occurred when Mundus bluntly offered Paulina 200,000 drachmae for her, er, company one night. She was mortally offended at such a coarse suggestion.

Mundus was despondent, so great was his lust for Paulina, her wedded state notwithstanding. He decided to starve himself to death. His slave, Ide, took pity on him and opined that the priests of the Isisian Cult might be able to help. On Ide’s suggestion, Mundus offered two corrupt elders in that temple 25,000 drachmae each – a bargain compared to what had been turned down earlier by Paulina herself – to assist him with his carnal quest, and they agreed.

The priests went to Paulina and told her that, in a stunning revelation, Anubis the jackal-headed god had appeared to them and said he wanted to enjoy Paulina’s beauty himself. Paulina was flattered – a god wanted to ravish her! – and ran to tell her husband that Anubis desired her to “sup and lie” with him as soon as possible.

I mean, seriously, what response could Saturninus possibly have given under these circumstances other than ‘that sounds wonderful, dear’?

your blind date

your blind date

At the appointed time, Paulina showed up at the Isisian Temple – I guess Isis was pimping for her fellow god? – had a lavish dinner with Anubis (though he remained invisible and silent throughout the meal) and then retired to the prepared bedchamber. In total darkness, Mundus slipped out from behind the curtains and proceeded to have his way with Paulina all night without uttering a word or exposing his face to light.

Must have been some performance to pass for a diety’s without arousing suspicion.

Paulina went home in a state of ecstasy. Mundus, like too many foolish lotharios before and since, crowed about his conquest. Word got back to Paulina and Saturninus that they had been duped.

That power couple, though, was not without recourse, as they were good friends with the Emperor Tiberius. The Emperor immediately took measures to avenge the dishonor of Paulina. He razed the Temple of Isis to the ground, threw her statue in the river, and suppressed her cult and those of the other Egyptian deities, not the least of them Anubis’. Finally, he ordered that the slave Ide and the two priests be crucified.

As for Decius Mundus, he was merely banished from Rome, as Tiberius decided that what he had done was only performed “out of misguided excess of the passion of love.”

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A Royal Petition

One evening two summers ago, after reading an article about extinct British titles over a bottle of merlot, I composed a letter to Her Majesty informing her of my interest in rectifying that situation:

Post Office Box ___
Cary, North Carolina 27512 USA
13 June 2011

HM Queen Elizabeth II
Buckingham Palace
London SW1A 1AA England UK

Your Majesty:

I am a proud Canadian and citizen of the Commonwealth, the son of a proper Englishwoman, currently living to the south in your former rebellious colonies in North America. My ancestral bias aside, no thinking person can doubt that British enlightenment civilized the globe and brought the rule of law to the darkest corners of all continents. Erstwhile rebellions and ill-conceived whimsy of self-governance notwithstanding, as with bell-bottom slacks and men’s wide neckties, I am certain that the pendulum will swing again and those malcontents who have floundered at independence will once more clamor for the stability, prestige, and unrivaled pageantry afforded by the Crown.

I am ready to assist when that happens – nay, I wish to be in the forefront of that movement!

I graduated from the College of William & Mary in Virginia (founded in 1693 by Royal Charter from your second cousin eight times removed!) and additionally I have been granted arms by the Canadian Heraldic Authority. If that were not enough, I consume tea before coffee, stout before beer, gin (with tonic and lemon) before tequila or vodka, scones before biscuits, and fish-n-chips before all other manner of sustenance.

From extensive study of the peerage, I have learned that a number of ancient and venerable titles remain extinct or dormant at present. That trifle misunderstanding at Runnymede and the unpleasantries with Lady Jane Grey, Cromwell, and the dreadful Jacobites aside, the ennobled worthies of the Empire have usually been a trustworthy font of support for your forebears and the Crown. It is a pity, therefore, that your prerogatives as Queen of the Realm and Territories, Head of the Commonwealth, and Defender of the Faith are not being fully exercised by letting these honours sit idly when they could instead be filled with those actively doing your royal bidding.

For example, I understand that the Dukedom of Kintyre and Lorne, the Marquisate of Wigton, the Earldom of Carrick, and the Barony of Annandale have all been extinct since 1602. The Dukedom of Montagu has been extinct since 1790. The Dukedom of Ancaster and Kesteven has been extinct since 1809. Those are awfully long periods of inactivity. The castles must need a thorough cleaning by now!

Madam, I can hear you say, “but what does this colonial know of being a peer?!” I have a ready solution for that. Perhaps you would rather allow me a non-peerage ‘starter’ title instead? Given that your 9th great-grandfather, James I, established Baronetcies for the investment of a mere £2000 – a bargain if ever one did exist – I would be happy to contribute to the Exchequer for such an opportunity (after Wills’ and Kate’s nuptials, I suspect the Exchequer would be delighted.) In addition, no one would be burdened to find an extra folding chair for the House of Lords.

The Halkett Baronetcy became extinct in 1705, while the Baronetcies of Halford of Welham and Hales of Woodchurch and Tunstall became extinct in 1720 and 1829 respectively. Dare I note that the Baronetcy of Wolfson of St Marylebone has only been extinct for thirteen months?! That seat is probably still warm!

I know, Your Majesty, that you will make a wise decision. To ease in the process, I have included a recent copy of my curriculum vitae. You will see that I am an accomplished professional and academician. As a germane aside, I have no unseemly legal issues of which to speak – I did run afoul of the constabulary in Bath when I was surreptitiously photographed last year in my rental car in a ‘buses only’ lane, but it was wholly unintentional and has long since been settled to the satisfaction of all.

On your command, the Registrar of the Peerage and Baronetage can easily attend to the above suggestions with minimal paperwork on your part required. For such comparatively little effort, having at the ready a titled and enthusiastic subject, such as myself, sworn to fealty, will be to the benefit of all when the clarion call is heard!

I have the honour to be Your Majesty’s most humble and obedient servant,


Despite the aforementioned consumption of vino, I remembered to spell ‘honour’ as such, and not as ‘honor.’

Before long, a reply:

Buckingham Palace

26th July 2011

Dear Doctor:

The Queen has asked me to thank you for your letter of the 13th of June informing her of your wish to become a British Peer. Her Majesty has taken careful note of your comments. I must inform you, however, that this is not a matter in which the Queen would intervene. I am sorry to send you a disappointing reply. Nevertheless, please accept my best wishes for the future.

Yours Sincerely,

Sonia Bonici,
Senior Correspondence Officer

I am pleased to report that, despite my billet doux, I have traveled to the U.K. since this exchange without detention by the Border Agency of HM Home Office, and I am therefore not apparently on any ‘watch lists.’ Yet.

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Thomas Rowland, highwayman

On this date in 1690, a highwayman named Thomas Rowland was hung at Tyburn, the execution ground for the city of London since at least the 12th century.

The Gallows at Tyburn

The Gallows at Tyburn

He had been a bricklaying apprentice before deciding that robbery was a more exciting and lucrative career. Interestingly, he committed his crimes dressed as a woman, the disguise helping him to stay at large for almost two decades (though it should be noted that when fleeing the crime scene in drag, he rode astride his mount and not side-saddle, his attire notwithstanding).

The condemned of the era were held at Newgate Prison near the Old Bailey in London before being transported by ox-cart to the killing field. Newgate, however, was not managed as we might expect of a prison today. Male and female prisoners were commingled, as were those of different degrees of offense and age. Newgate, you see, was a profit-making enterprise; the Keeper (warden) paid to assume the position, with the expectation that he would then profit from the prisoners, who were expected to pay for food, clean water, visitors of all stripes, alcohol (!!) and the more desirable cells.

As was traditional at these public events, the Ordinary (chaplain) of Newgate Prison accompanied the condemned to the gallows and exhorted them to repent at the last minute, so that they could present a cleansed soul to the Almighty at the Pearly Gates.

Said obdurate Thomas Rowland, however, would have none of this morality play, according to contemporary accounts. Not only did he refuse to confess and repent, but one observer noted that he “was so abominably wicked that the very morning on which he died… a common woman of the street [came] to visit him, [and] he had the unparalleled audaciousness to act carnally with her, and gloried in the sin as he was going to execution.”

He must have had some explaining to do to St Peter.

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Cotard’s Syndrome

“Yes, I’m warm, but things give off heat as they rot. And I suppose it is a pulse… but it’s a very weak pulse.”
~a former patient with Cotard’s Syndrome

Attending on a high-security forensic psychiatric ward has some perks for the curious of mind. The civil libertarians might not approve, but there is a little-realized facet of pre-trial evaluations that provides clinicians an opportunity to observe patients for far longer than would be the case in just about any other venue. You see, if a person is charged with a serious felony but is found incapable mentally of proceeding to trial, they will remain in a secure inpatient setting until such time that 1. they are restored to capacity to proceed, or 2. the charges are dropped. When the charge is, say, murder, prosecutors are reluctant to appear ‘soft on crime,’ but if the person is so mentally unstable that they might never be restored to capacity, you have a situation in which a person not convicted is nevertheless confined for indefinite periods of time in medico-legal limbo.

With 3d party payors wanting patients out the door in a matter of days, this limbo affords a clinician opportunities to observe pathology over a far longer span than would otherwise be possible in an inpatient setting. Just try getting Blue Cross Blue Shield to approve a hospital stay of fifteen years or more.

I will now dispel another fantasy held by many not involved in forensic psychiatric work: that it’s all like FBI profiling or CSI on television. It’s not. Much of it is routine and repetitive. Patients are admitted with symptoms of depression and anxiety (common), garden-variety schizophrenia (common), malingering and substance abuse (very common), and a smattering of less frequent conditions.

And then once in a very long while, perhaps a single time in a career, you see something astoundingly rare. It happened to me.

First some background: Jules Cotard, a former French army surgeon in the Franco-Prussian war who practiced at Hospice de la Salpetriere outside Paris, saw a female patient in 1880, whom he called Mademoiselle X. She held the belief that she was dead. Not a suicidal desire to die, mind you, but already dead. Patients with this particular condition maintain that they have died and, sometimes as an added delusion, are missing vital internal organs, an intact body, or a soul. They espouse being walking rotting corpses – totally utterly dead. Mdmse X had just such a presentation. She was convinced that she had no blood, no heart, and was a moldering cadaver. No amount of reassurance or production of evidence as to her actual state convinced her otherwise. She stopped eating – why would a corpse need to eat? – and eventually is said to have expired of starvation. Cotard called the condition le délire de négation, or nihilistic delusional state, but 21st century lay readers may know it better from media sensationalism as Walking Corpse Syndrome.

Delusions in general are challenging to understand and explain (and treat), especially to those in training or whose psychiatric patients to date have been middle class suburban neurotics on low-dose Prozac. A delusion is a fixed and unshakable belief that runs counter to reality and all evidence to the contrary. Delusions are insidious in that they usually do not appear overnight; there is almost always a prodromal phase in which the patient-to-be begins to focus on unusual ideas that might trigger some alarm amongst friends and family, but haven’t by that point reached the level where emergent psychiatric intervention is sought. Despite the detachment from reality, delusions do not involve visual or auditory hallucinations. While some delusions are fantastical (e.g., Martians have landed), others are entirely plausible (e.g., being followed), making their diagnosis difficult until the weight of evidence leaves no other choice. There are paranoid delusions – that spies or law enforcement are monitoring one’s actions. There are grandiose delusions – that one is famous and wealthy. There are erotic delusions – that a newscaster or movie actress is one’s secret lover. A delusional state likely drove John Hinckley to attempt to assassinate President Reagan. Delusional thoughts were reportedly evident in the suicide note left by the recent Washington Navy Yard shooter. Anna Anderson, the woman who claimed for decades to be Grand Duchess Anastasia of the House of Romanov, almost certainly suffered from delusions.

The beliefs espoused by those with Cotard’s Syndrome, in extremis, basically are no different. While Cotard’s Syndrome is not a freestanding diagnosis within the Diagnostic and Statistical Manual at present – possibly a reflection of its rarity – its psychotic presentation is solidly within the realm of the delusional. And while delusions of death are its hallmark, other aspects of the syndrome, such as the cessation of eating and bathing, or tactile hallucinations of worms eating the corpus, are unquestionably related. There is even one documented variant of a Cotard’s patient espousing immortality, premised on the belief that if he were dead but still able to talk and think, he must be a god. Go figure.

Cotard believed that there are two stages in the disease’s progression. For those more fortunate (?), the early phase, which was called germination, involves a psychotic depression with a fixation on hypochondriacal topics. If the patient is lucky, it will arrest there, and at least at present, with antidepressant medication and electroshock therapy, prognosis is guarded but not hopeless. Those who progress on the continuum, however, like Mdmse X, develop unremitting delusions of present-tense death, often resulting in a self-fulfilling prophesy of sorts.

And interestingly, Cotard was probably not the first person to recognize the condition. An English physician, Charles Bonnet, described the case of an elderly female patient in 1788. She had been hit by a sudden cold draught in the house, the story went, and instantly came to realize that she was dead. She insisted on being stretched out in a coffin and hosting a wake. Apparently she was fussing over the way her burial shawl was arranged during her own memorial. Once she fell asleep, her family moved her to bed, and with treatment that included the ingestion of ground precious stones and opium (!), she is said to have improved over time, but would still relapse every few months. Why this condition is not know as Bonnet’s Syndrome I am not certain, except that from the vantage point of two centuries, the elderly woman with the draught seems far more histrionic than do those with a profoundly neurovegetative state manifested in fulminant Cotard’s Syndrome.

I have searched the medical literature on this subject and found few scientific articles. Cotard’s Syndrome itself appears rare; however, somatic (bodily) delusions become more common if the diagnostic net is cast wider and other entities are included – these aren’t ‘pure’ Cotard’s Syndrome, but they share clinical features. For example, those with schizophrenia often have irrational thinking, although there is no evidence that their delusions are more likely to involve present-tense death. Bipolar disorder can produce psychosis at the extremes of mania and depression, but these symptoms clear when the patient returns to a euthymic, or ‘even keeled,’ state. Certain medications can effect profound mental status changes, but such suggests a transient toxic delirium and not a more intractable delusion (i.e., as far as we know, Cotard’s can’t be ‘fixed’ by dialysis and metabolic homeostasis alone). Strokes can manifest a state called asomatognosia, in which a patient loses awareness of parts of the anatomy on the afflicted side of the body. Traumatic head injuries can yield disorganized and delusional thoughts, as can subsequent or unrelated seizure activity, end-stage liver failure, tumors, dementia, and even severe migraines – but none of these are Cotard’s.

Almost nothing is known of the actual pathophysiology of Cotard’s, except that PET scans have revealed a markedly decreased level of glucose metabolism in the (admittedly few) patients with the condition who have been studied. The degree of decreased metabolism is similar to, but markedly more than, that seen in patients taking certain tranquilizers, or those under anesthesia or in vegetative states.

In many ways, Cotard’s Syndrome is related to Capgras Syndrome, since both are seen as disconnects in the parts of the brain that govern recognition and related emotional response. Capgras’ Syndrome is a delusional state in which a patient believes that familiar faces are actually those of imposters. If synapses in pertinent parts of a patient’s brain malfunction and this recognition system fails – what psychiatrists call derealization – one develops Capgras’ (if one is viewing others) or Cotard’s (if one is viewing self). Or at least that’s the theory.

In 26 years of clinical practice, I have only encountered once a patient with Cotard’s Syndrome. It was while I was attending on a long term forensic unit at a state psychiatric hospital. At the time I only had a vague recollection of what was Cotard’s; it’s not really a subject stressed in medical schools or residencies, being subsumed by the larger taxonomic umbrella of (generic) ‘delusional disorders.’ I remember my patient as an elderly black male of wiry build with short graying hair and, surprisingly, a ready smile when addressed. He was also in good physical health – he had no known history of head injuries, epilepsy, migraines, cardiac disease, cirrhosis, or malignancies. He also did not have schizophrenia, bipolar disorder, or dementia, and was not delirious while on my service. As a matter of fact, except for having little formal education, he seemed ‘normal’ on the surface if not always talkative.

Patients suffering dementing processes can often appear cognitively intact if an interview lacks depth; this is because these patients can initially cover their deficits with socially expected superficialities. The same can hold true for other psychiatric illnesses. In the case of my patient with Cotard’s, if one didn’t bring up his mortal condition, he could talk about ward activities and the weather and what he had seen on television without any problem. But if one brought up the state of his health, he’d say, in no uncertain terms, that he was dead. Psychological testing – repeated over time – did not show evidence of malingering or over-endorsement of symptoms, and this fact, along with his consistent clinical presentation over the years, suggested that he was the ‘real deal.’

And as with almost all other delusional disorders, if you engaged my patient in a discussion of his physical state, no matter how persuasive your logic, he had a ready explanation for why that just wasn’t so. Why did he eat and drink? Well, it was an activity he picked up while alive, one that he did now merely out of force of habit after more than 70 years. Why was his blood still liquid and red when drawn for labs? He hadn’t been dead long enough for it to have coagulated. Why did he sleep? He didn’t actually sleep – he just lay in bed with his eyes closed so that he could concentrate on the worms eating him. Why did he bathe? Corpses don’t need to bathe since they don’t sweat (the bathing part was accurate… he rarely attended to hygiene unless forced). And so on.

Treatment? Therein lies the problem. If delusions of death stem from a psychotic mood disorder, the treatment can include antidepressants, anticonvulsants, lithium, and shock therapy, with a fair prognosis. However, when the delusional symptoms are not caused by another underlying etiology, the response to treatment is often poor and incomplete. In my experience, antipsychotic medications, for example, render such a patient less likely to verbally express delusional thoughts, but the thoughts are still ‘in there’ – as was seemingly the case with my patient. Though I later moved to a new position in a different hospital, I have learned since that he’s still hospitalized. And still incapable of proceeding to trial. And still ‘dead.’

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[Copyright 2013 @ The Alienist’s Compendium]

The Capitol Basement… and the 21st Amendment

When I was in high school, I served one summer as an intern on Capitol Hill for Senator Herman Talmadge (D-Ga). Though I only lived a few miles away in northern Virginia at the time, it was an exciting experience for a young man thrust into a world of power and privilege that seemed a vast distance from routine suburbia.

The ‘We Are Not In Kansas Anymore’ aspect of this was especially driven home for me when I observed that Senator Talmadge had an antique spittoon by the huge mahogany desk in his office – and used it regularly. He remains the only person I’ve met in my life who possessed a spittoon for anything other than decoration.

Anyway, on my first day as an intern, the Senator’s legislative assistant called me into the antechamber. He was a bookish looking fellow then in his late 30s who bore an uncanny resemblance to John Dean of Watergate fame. He opened his wallet and pulled a $20 and instructed me to go out to Constitution Avenue and hail a cab and tell the cabbie that I needed to be taken to an address on Pennsylvania Ave NW and ask for Christian and pick up a package. I was thrilled. I thought, “I wonder if that’s the address of a foreign embassy? Or a government think-tank? A powerful lobbying firm? Maybe it’s a secret enclave of the intelligence community!” I tried to appear as nonchalant as a 17 year old can look in this setting, but suspense got the best of me. I asked where I was going. He replied, “I was at the 21st Amendment last night (a famous but now extinct watering hole of the 1970s located in Foggy Bottom) and I got really shitfaced and had to walk home. I forgot my car keys, and I need for you to go and fetch them for me.”

So much for the start of my career with elected public servants and their minions.

But that’s not really the subject of today’s post.

While I was with Senator Talmadge in the Dirksen Office Building on the Hill that summer of 1979, I discovered the Capitol Subway deep in the basement. This “subway,” if you can really call it that, is more of an electric people-mover that connects the basement of the Capitol building proper with the office buildings of the U.S. Senate and House of Representatives nearby. The underground track was first installed in 1909 to connect only the Russell Senate Building with the Capitol through a narrow tunnel.

In 1960, an operator-controlled monorail was installed for both the Dirksen and Russell Senate Buildings, replacing the original primitive rolling stock. This was the system with which I was familiar. In 1963, the Rayburn House Building had its own line installed to the Capitol. And finally, in 1982, the Hart Senate Building was given a subway stop, though that didn’t exist when I was on the Hill.

1909 Subway I (courtesy Office of the Capitol Architect)

1909 Subway I (courtesy Office of the Capitol Architect)

1909 Subway II

1909 Subway II

An interesting quirk of construction: the Senate and House lines don’t connect, but rather terminate at different points in the Capitol’s basement, and one must navigate a labyrinth of tunnels to travel between the two. Only the truly initiated can hope to do this without getting lost.

When I was on the Hill, there was no turntable for the rolling stock at each terminus, as the cars went back and forth on the tracks without turning around. Because of this relative simplicity, by 1993, the live train operators had gone the way of the dodo bird and the system became fully automated.

Back then, the public could just get onboard for the 1200’/ 52 second ride between Dirksen and the Capitol. Now anyone not an employee has to be escorted by a staff member with proper ID, so the Great Unwashed are no longer welcomed. And even with escort, during sessions, any rider not a Senator or Representative runs the risk of being bumped to facilitate The Elected getting to the chambers in time to cast critical votes.

I still remember vividly the wind whistling through my hair as the open-topped glass-sided cars whisked down the dark tunnel at top speed of 17 mph.

The subway I remember

The subway I remember

And the subway isn’t the only odd thing in the Capitol’s basement.

Way back in 1860, given the muggy Washington summers and the lack of climate control – remember that the District of Columbia was originally a swamp that had been drained – it was decided by the Architect of the Capitol to install private baths in the basement of the building. Not just ‘regular’ bathtubs, mind you, but tubs stylishly carved into 3’ x 7’ cisterns from single blocks of solid Carrara marble imported from Tuscany. The Architect ordered six to be handmade in Italy and shipped over here.

Legend has it that elected officials could be banished from chambers if they stunk, followed by instruction to bathe and come back smelling better. The marble tubs in the basement weren’t only functional, though – they were also relaxing and luxurious, since even Senators and Representatives in antebellum days didn’t usually have running water at home.

With the coming of the Civil War, the tubs were soon forgotten. Only two of them are now extant, both on the Senate side, located deep in the bowels of the HVAC rooms downstairs.

Leading Back to the Tubs

Leading Back to the Tubs

When I last saw the tubs, in 1980, they were still impressive, smooth and polished with fancy tile surrounding the steps leading up to each that hinted at the former grandeur of that private enclave.

One of the Tubs

One of the Tubs

I’m glad I got to visit them when I did. I doubt, after 9-11, that curious interns can access the subterranean vaults any longer.

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[Copyright 2013 @ The Alienist’s Compendium]

Phineas Gage

In writing this post, I tip my hat to two authors, the works of whom I admire: Bess Lovejoy, who wrote Rest in Pieces: the Curious Fates of Famous Corpses, and Colin Dickey, who brought forth Cranioklepty: Grave Robbing and the Search for Genius. These tomes, far more than anything in formal medical training and experience, opened my eyes to the fact that there are a lot of bodies out there who are missing their heads.

In the spirit of cooperation, I’d like to add yet another name to history’s decapitated roll call.

Any student of neurology or psychology has heard of Phineas Gage. An otherwise unremarkable 19th century laborer, Gage has earned eternal notoriety, not for his professional competence, but for an accident he did not anticipate and the consequences of which he could never have imagined.

Gage was born in 1823, the first of five children to Jesse Gage and his wife Hannah, in Grafton, New Hampshire. Little is known of his childhood, but it is suspected that he gained experience with explosives as a youth at mines and quarries near the family farm. He later went to work as a foreman on railroad construction projects in New England. His employers considered him “the most efficient and capable…. [v]ery energetic and persistent in executing all his plans of operation.” Gage, it is said, even had a tamping iron custom made to specifications for his work with explosives; this iron, a sturdy rod 3’7” in length and 1.25” in diameter, was used to set charges along the right-of-way during construction.

Little did Gage realize that his custom iron rod would be his lifelong companion in a manner far different than that originally intended.

On the day in question, 13 September 1848, Gage was working with his crew on the Rutland & Burlington Railroad near Cavendish, Vermont. They were blasting rock to prepare the roadbed for the laying of rail. Setting an explosive charge involved boring a hole deeply into the rock, adding blasting power, a fuse, and sand, and then compressing the charge in the hole using the tamping iron. Around 4:30 p.m., Gage was doing this for one of the day’s last charges – perhaps he was getting tired toward the end of the shift? – when the powder detonated prematurely. The tamping iron rocketed out of the hole and like a javelin penetrated the left side of Gage’s face, passing in back of his left eye, and exiting the top of his head (the iron, weighing over 13lbs, was later found 90 feet away, “smeared with blood and brain”). Gage was thrown on his back and convulsed. All those present said later that they were certain he was dead. But within a few minutes, accounts agree, he was able to speak coherently, and he was then transported to his lodgings in town, almost a mile away, by oxcart.

Gage Skull (courtesy of Harvard Univ)

Gage Skull (courtesy of Harvard Univ)

The first physician to reach him, a Dr. Edward Williams, arrived at his bedside less than an hour after the accident. Dr. Williams said he could see the pulsations of Gage’s brain through the exit wound. Gage then vomited, and Williams noted that expelled from the exit wound was “a half teacupful of brain which fell upon the floor.” For three weeks, Gage went in and out of consciousness as his friends and family kept vigil, expecting his passing at any moment. A coffin and burial clothes were kept nearby. But by November Gage was able to walk short distances with assistance, and he then returned to his parents’ farm to further convalesce.

Gage lost vision in his left eye and had left sided facial paralysis as well, plus considerable scarring. Yet he survived a grievous head injury in pre–antibiotic and –neurosurgery days, a trauma that would challenge a 21st century physician and ICU. It was a wound that one of his attending physicians at the time called “the case which more than all others is calculated to excite out wonder, impair the value of prognosis, and … subvert our physiological doctrines.” It was a rare clinical situation which could have provided his doctors an unparalleled chance to study the function of the human brain theretofore unknown and mysterious.

Gage lived for a dozen years after the accident, eventually working in a livery, as a farmhand, with Barnum’s American Museum (as an exhibit), and even as a stagecoach driver at one point. He is said to have been able to perform most tasks with in a structured environment. But even though he regained basic social and employment abilities, friends and family said he was “no longer Gage.”

Phineas Gage (courtesy of Harvard Univ)

Phineas Gage (courtesy of Harvard Univ)

But to what extent was he “no longer Gage”? A latter-day rhyme opined that,

A moral man, Phineas Gage
Tamping powder down holes for his wage
Blew his special-made probe
Through his left frontal lobe
Now he drinks, swears, and flies in a rage.

Though Gage’s has been held as the index case regarding personality changes following frontal lobe trauma, its scientific value is compromised by the uncertain extent of the brain damage and the small amount objectively documented in detail about the changes. Instead, psychologist Malcolm MacMillan writes in An Odd Kind of Fame: Stories of Phineas Gage, that the story “is primarily worth remembering because it illustrates just how easily a small stock of facts becomes transformed into popular and scientific myth.”

Modern writers and urban legend often portray the post-injury Gage as a restless, profane, irritable, and unpredictable psychopathic lout, unable to hold a job, who then becomes a drifter, dying in penury. This exaggerates the behavioral changes far beyond that written by anyone who actually knew and interacted with him. What real value could have been gathered from study of Gage’s recovery was lost by the lack of detailed documentation, and the absence of imaging and neuropsychological testing, still decades in the future. Dr. John Harlow, one of Gage’s attending physicians, only hinted at non-specific neurological changes in his patient, saying, “the mental manifestations… I leave to a future communication [as this] case is exceedingly interesting to the enlightened physiologist and intellectual philosopher.” The Chair of Harvard’s surgery department at the time, Dr. H.J. Bigelow, went so far as to later state that Gage was “quite recovered in faculties of body and mind,” there being only “inconsiderable disturbance of function” to show for the injury.

Still, studying the post-accident course of a man so seriously maimed yet alive was an opportunity for scientists and physicians to at least start thinking about the brain and what parts govern which aspects of function and personality.

What is not debated is that over the years, Gage’s seizures increased, and he began to experience grand mal events that were longer and more frequently. He died in status epilepticus on 21 May 1860, and was buried in Lone Mountain Cemetery just outside of San Francisco.

And so the story ends. Not.

“It is regretted that an autopsy could not have been had so that the precise condition of the encephalon at the time of [Gage’s] death might have been known. In consideration of this important omission, the mother and friends, waiving the claims of personal and private affection, with a magnanimity more than praiseworthy, at my request have cheerfully placed his skull (which I now show you) in my hands, for the benefit of science. I desire, here, to express gratefully my obligation, and those of the profession, to D. D. Shattuck, brother-in-law of the deceased [and others] for their kind cooperation in executing my plans for obtaining the head and tamping iron, and for their fidelity in personally superintending the opening of the grave and forwarding what we so much desired to see.”
~Harlow (1868)

Dr. Harlow had learned years later that his famous former patient had expired on the west coast. The doctor immediately took to corresponding with Gage’s family, and with chutzpah unthinkable to 21st century mores, asked for the body to be exhumed and the desired specimen brought back east. With the family’s permission, Gage’s grave was indeed opened seven years after interment and his skull was removed – along with the tamping iron, which had been buried with him. Both items were shipped to New England and personally presented to Dr. Harlow.

The skull and iron remain on display in the Warren Anatomical Museum of Harvard’s medical school to this day. The rest of Gage is still in California.

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[Copyright 2013 @ The Alienist’s Compendium]

A Miscarriage of Justice?

The acquittal, by reason of insanity, of John Hinckley in 1982, after he shot President Reagan and three others, was held by many to be a miscarriage of justice. In the decision’s wake, reforms were instituted on both the federal and state levels, tightening up (and in some cases eliminating) the insanity defense.

The interesting aspect of that hue and cry is that this was not the first time that allegations of misuse of that affirmative defense had been raised, and it was arguably not even the most egregious instance.

In follow up to this week’s earlier post about the medicinal use of alcohol during Prohibition, I bring you the now-little-remembered insanity case of George Remus. He was an erstwhile pharmacist and attorney, and then the major bootlegger in the Midwest during the 1920s. He had read the Volstead Act with a lawyer’s eye for loopholes. Accordingly, you will recall that Remus created a front corporation, the Kentucky Drug Company, Inc., through which he was able to procure and ship ‘medicinal’ booze all over southern and central United States. In less than three years, Remus made almost $40 million.

George Remus (courtesy Ohio Historical Society)

George Remus (courtesy Ohio Historical Society)

His is a name that is frequently suggested as being the inspiration for the character of Jay Gatsby in F. Scott Fitzgerald’s 1925 novel. And true to his purported fictional character, with all that money, Remus threw some pretty lavish parties with his second wife, Imogene (the daughter of a prominent local family as well as his secretary, with whom Remus had been caught in flagrante delicto by first wife Lillian). This second marriage scandalized many of the Cincinnati bluebloods – but that didn’t stop the Brahmins from attending a number of Remus’ extravagant fêtes, including a notable 1923 birthday bash for Imogene in which she appeared in a daring bathing suit along with other aquatic dancers, serenaded by a fifteen-piece orchestra. Another notable soirée was the New Year’s bash from later that same year, at which one hundred prominent families were fed and watered, and then, as parting gifts, presented by Remus with diamond watches (for the men) and brand new Pontiacs (for the wives and mistresses).

The law finally caught up with Remus and he was convicted of violations of the Volstead Act, receiving, though, a relatively brief sentence. While incarcerated, he met an undercover federal agent to whom he inadvertently revealed much concerning his hidden money. That officer promptly resigned his post, started an affair with Imogene on the outside, and the two of them proceeded to pilfer and hide as much of the ill-gotten millions as possible while Remus sat behind bars. Imogene then graciously mailed Remus five twenty-dollar bills for his prison bank account.

Remus was finally sprung from prison, and Imogene filed for divorce. She donned an elegant black dress and hailed a cab on the day the court was to finalize the marital dissolution. En route to the courthouse, on 6 October 1927, Remus tailed his estranged wife, and then had his chauffeur force her cab off the road in Eden Park. Remus jumped from the Cadillac sedan brandishing a weapon. Imogene tried to escape on foot through rush-hour traffic, but the enraged former bootlegger caught her and fired four shots from his .45 directly into her abdomen in front of scores of onlookers near the Spring House Gazebo. He then calmly awaited the police.

Messy. And potentially difficult to defend.

The prosecutor in the subsequent murder trial was 30-year-old Charles Taft, the son of U.S. Supreme Court Chief Justice (and former President) William Howard Taft. It looked like an open-and-shut prosecution. But Remus, the former lawyer, defended himself on theories of “morally justified homicide” and then temporary insanity. The prosecution countered with prominent psychiatric expert witnesses saying that the defendant was entirely sane.

[sidebar: over the years I’ve heard several times from my forensic patients charged with murder that their victims “needed killin’.” Perhaps they were merely referencing Remus’ unusual theory of “morally justified homicide,” whatever that is]

What Taft hadn’t anticipated was Remus’ popularity in Cincinnati. After closing arguments, the jury only deliberated 19 minutes before returning a verdict of not guilty by reason of insanity. The legal community was shocked. The wiley Remus then paraded the same expert witnesses earlier employed by the prosecution and had them repeat their assertions that the respondent – Remus – was entire sane (and by extension not in need of commitment to an asylum). It worked. Remus was released after only six months, and had basically gotten away with murder, whether Imogene “needed killin’” or not.

Remus tried to get back into bootlegging in 1929, but lamented to colleagues that the market had been taken over entirely by “lowlifes and gangsters.” He lived the remainder of his life quietly and modestly, dying of natural causes at age 77 in 1952.

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[Copyright 2013 @ The Alienist’s Compendium]

Rx Booze

When I started my training in the mid-1980s, there were still nurses working at the medical center who remembered early in their own careers keeping a refrigerator on the ward that was filled with cans of beer, which the docs would prescribe for patients who were undergoing alcohol withdrawal. Prescribing beer would allow a gradual taper of their daily consumption, and would prevent their going into full-blown delirium tremens while inpatient.

Prescribing beer worked just fine in avoiding DTs before benzodiazepines were available. But it also represented a throwback to a time when medicinal use of alcohol was not nearly so innocent and altruistic.

In my post from last week on cresol, I made the observation that “if one presumes that humankind’s search for euphoria and an altered state of consciousness is not going to vanish anytime soon, then substance abuse is a problem that is here to stay.”

For this reason alone, it should have been painfully evident to policymakers that the 18th Amendment to the U.S. Constitution, enforced by the National Prohibition (Volstead) Act, was doomed to failure.

For thirteen years starting on 16 January 1920, there was a ban on the production, sale, and distribution of alcohol in the United States. But like most futile social policies, there were legal loopholes, plus illegal ways to circumvent the law, that were big enough through which to drive a Model T delivery truck. Farmers, for example, were allowed to grow grapes and produce wine (up to 200 gallons per growing season for their own consumption) under the guise of “preserving fruit.” Rabbis and priests could obtain wine, and congregations could partake, during religious ceremonies.

And physicians (as well as dentists and veterinarians) were allowed by the Treasury Department to prescribe alcohol for ‘medicinal purposes.’ Over 15,000 physicians applied for this privilege in the first six months of Prohibition alone. Having added special licensure allowed physicians to write up to 100 prescriptions for medicinal alcohol per month – a numerical allotment that was rarely if ever underutilized. Hooch was accordingly used to ‘treat’ a variety of ailments, including cancer, asthma, difficulty with lactation, diabetes, poor circulation, snakebite, anemia, typhoid, pneumonia, tuberculosis, coronary artery disease, high blood pressure, indigestion, depression – even the wonderfully vague and non-specific ‘old age.’ And if alcohol wasn’t listed as treatment for one’s ailment-du-jour, booze was still often used as a vehicle by which to ease the ingestion of other medications, as it tasted better than many pharmacy preparations.

Rx pad (courtesy Rose Melnick Medical Museum)

Rx pad (courtesy Rose Melnick Medical Museum)

So much for bubble gum flavored cough syrup.

Rx pad (courtesy Rose Melnick Medical Museum)

Rx pad (courtesy Rose Melnick Medical Museum)

Pharmacies were required to apply to be alcohol-dispensing entities. Some states were stricter than others, but especially near the Canadian and Mexican borders, and on the coasts, rules were often more lax and supplies were vast and difficult to control – pharmacies had no trouble keeping firewater in stock and their ‘sickly’ customers supplied. Prescriptions were filled for spiritus frumenti, or spirit of the grain, the term of art by which most physicians documented the necessary libation. Patients would quickly take such a prescription – they expired after three days – to a pharmacy and request the type of liquor they desired: gin, rye, scotch, whatever. Toward the end of Prohibition, when the sham was so obvious that hardly anyone even cared, more than a few pharmacies were actually filling prescriptions for champagne. And while some druggists only carried cheap alcohol better suited for cleaning, and often watered it down, it was apparently not rare that alcohol handed over the counter was brand name stuff like Jack Daniels in recognizable trademarked bottles – as long as it had a label affixed that said, “for medicinal purposes.”

See anything potentially analogous here vis a vis medicinal marijuana?

Anyway, doctors were supposed to be examining and diagnosing patients before any prescriptions were dispensed, but that stipulation was largely flouted. Every ten days, a patient willing to cough up the cash for a rote office visit could walk out with prescription-in-hand and shortly thereafter, down the street, head home with a pint of booze. There might have been some people who were given the tipple for actually-perceived medical need, but the whole process really just became a means by which physicians and pharmacists could earn a few extra bucks during hard times.

Doctors’ instructions varied, but generally they advised their patients to imbibe an ounce of alcohol every few hours or a tablespoon three times a day. One of my favorites was from a prescriber in Detroit in 1926: “take three ounces every hour for stimulation until stimulated.”

Those not even in the medical profession took notice. Bootlegger (and lawyer) George Remus incorporated a sham business entity called the Kentucky Drug Company. As a licensed supplier, this front allowed him to legally obtain and transport alcohol in company trucks to pharmacies all over the Midwest and South – that is, when he didn’t have his men hijack his own trucks en route and then divert the contents to speakeasies nearby.

The farce finally ended when Prohibition was repealed by the 21st Amendment on 5 December 1933.

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[Copyright 2013 @ The Alienist’s Compendium]

Beer Bottles

Shortly after the formation of his government, Prime Minister Winston Churchill delivered a speech to the House of Commons that would be committed to history with the title, ‘We Shall Fight Them on the Beaches.’ This oration, arguably Churchill’s finest and the one opined by journalist H.R. Knickerbocker as “deserv[ing] to be memorized by us all,” is that for which the great man remains best known and most often quoted to this day.

A less memorable part of the speech failed to make the newsreels and most history books. Thankfully.

The Prime Minister spoke on 4 June 1940. Holland and Belgium had capitulated weeks earlier. The French Republic was in its death throes, and the Battle of Britain was about to begin. The United States remained neutral, and the Soviets were not yet combatants. The situation was bleak, and Churchill had to deliver the news to Commons, and the public, that a great military disaster had befallen the Continent while not casting any doubt on the eventual outcome of the struggle.

Not easy to do.

The peroration – or dramatic summary – of his stirring rhetoric he gave thusly:

“We shall go on to the end.
We shall fight in France.
We shall fight on the seas and oceans.
We shall fight with growing confidence and growing strength in the air.
We shall defend our island, whatever the cost may be.
We shall fight on the beaches.
We shall fight on the landing grounds.
We shall fight in the fields and in the streets.
We shall fight in the hills.
We shall never surrender.”

Recordings of this moment reveal that Churchill then paused, both for apparent dramatic effect and because Commons thundered in applause and huzzahs. Due to the pandemonium that had erupted, though, no one was able to hear what Churchill said as he leaned down to an aide seated to his immediate right:

“And we’ll fight them with the butt ends of broken beer bottles because that’s bloody well all we’ve got left!”

Not nearly as stirring.

But as Paul Harvey used to say, now you know the rest of the story.

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[Copyright 2013 @ The Alienist’s Compendium]