Cat's Cradle

One of my favorite novels is Cat's Cradle by Kurt Vonnegut. Written in 1963, it is a ridiculous over-the-top science fiction book that satirizes science, religion, war, politics, the end of the world, and midgets. One of the more amazing things is that Vonnegut describes a fictional discovery of "ice-nine." A single molecule of this substance can "teach" molecules of normal liquid water to arrange themselves as ice-nine. It is as if one molecule of ice can seed water molecules to become that exact form of ice. This, ladies and gentlemen, is exactly what a prion does. I doubt this was the first time anyone proposed this idea, but I was amazed when I realized that Vonnegut in science fiction imagined a mechanism that decades later elucidated previously inexplicable diseases. In any case, Cat's Cradle is a really entertaining, thought-provoking, and highly recommended book.

How Now Mad Cow

Mad Cow Disease or Bovine Spongiform Encephalopathy interests me for many reasons. It's gotten so much press and media attention despite being incredibly rare. Indeed, people actually stopped eating beef whereas something like smoking has become so ingrained in our society that we don't even think twice when we see someone light a cigarette. But prion disease (mad cow is a type) is so weird because it involves infectious proteins. What? This goes against decades of biological dogma. Infectious organisms are things like viruses, bacteria, fungi. Aren't nucleic acids the only things that can self-replicate? How does an infectious protein make more copies of itself; there's no such thing (as far as we know) as reverse translatase. And how could prion diseases be sporadic, inherited, and infectious? Prions aren't destroyed by proteases, heat, radiation, or formalin. It just seems so bizarre and scary. Now that we know the mechanism of prion diseases, it hasn't stopped fascinating me. The very concept of something creating new copies of itself makes me think of those robots-take-over-the-world movies. I really realize Nature is a brilliant, cunning, and ingenious engineer.

Aerial Picture of UCSF, early 1960s

Source: http://history.library.ucsf.edu/

200

The history of UCSF is pretty interesting. In 1864, Toland Medical College was founded by Hugh Toland, a surgeon who came during the gold rush and stayed in San Francisco after the gold ran out. Toland Medical College became the Medical Department of the University of California in 1873 with the support of Richard Cole (hence the names of the classrooms Toland and Cole Halls). It wasn't until 1898 that the school moved to the Parnassus location, and in 1907, the first UC hospital opened. It's only a century later, and sometimes it's hard for me to figure out whether that's a lot of time or very little time. A few weeks back I heard a description of doctors that I really liked. A physician is someone who studies the natural history of diseases such that, given a constellation of signs, symptoms, and test results, he can diagnose and implement treatment for that disease. I like it because many essential people are part of the health care team, but doctors have the special training and expertise in diagnosis and procedural intervention.

Banter

One of the really fun things about BMB was a pseudo-rivalry between the course directors. Dan and Andy, two of the most enthusiastic and involved teachers for this block, had quite an entertaining feud. They would insert random slides into each other's talks, claiming that their topic was more interesting. I remember Dan giving an overview of the week and saying, "Now Andy is giving a lecture Wednesday morning. I would like to take this opportunity to remind you that lectures are indeed optional so feel free to sleep in that day." Of course to get him back, Andy's talk had embarrassing pictures from Dan's youth. They would fire off interjections from the back of the classroom; in response to a slide on "neuron networking," Dan would inquire, "you mean like speed dating?" But best of all, they had this thing where they would bring each other breakfast. It was very sweet. After a few mornings where they got each other orange juice, they began to scale up. One day, Andy came down and poured Dan a tiny bit of orange juice into a cup before reaching into his jacket pocket to pull out an airport bottle of vodka and pouring the whole thing in. The following week, Dan brought Andy breakfast, complete with a napkin tucked into his shirt, candles, and two med students serenading him on the violin. It was really really funny and really really awesome.

Huntington's Disease

The premise regarding Huntington's disease is simple. A child of an affected parent has a 50% chance of inheriting the autosomal dominant disease gene. Huntington's patients have movement problems, cognitive decline, and personality changes. There is no cure. There is a PCR test that can tell you if you will develop the disease. The question is, if you had a probability of inheriting the disease, would you take the test?

Some of the issues at hand include uncertainty, whether your plans would change depending on the test, financial, family, and educational planning. You may decide not to pursue that PhD or to get fetal testing or to travel the world. On the other hand, you may rather leave it up to God (or chance). You may become incredibly depressed if you have the mutation; you may be plagued with "survivor guilt" if you don't. Maybe you think ignorance is bliss; maybe you think knowledge is intrinsically valuable.

That's a lot to think about regarding a piece of knowledge for which there is no medical treatment. Thus, genetic counseling is central to those contemplating a test. But I like looking at Huntington's disease as an example of how knowledge is not inert. Just the prospect of knowledge transforms lives. This also says a lot about determinism and inevitability. The science of Huntington's disease is based on determinism. That is, the number of trinucleotide repeats in the Huntingtin gene causally determines whether (and when) someone will get the disease. Yet the disease is not seen as inevitable unless that information is known. The disease is determined by someone's genetics regardless of whether they test positive, but the patient only considers the disease inevitable if they test positive (hence the idea that not testing is "keeping hope open"). Until recently, I linked determinism with inevitability, but Dennett's Freedom Evolves that I'm reading has led me to doubt the solidity of that claim.

Brain Death

I'm glad we had a lecture on brain death. I think many people have some idea of what brain death means, but it's certainly an opaque topic. Brain death is a state equivalent to death. It is morally and legally permissible for a physician to withdraw life support from a brain dead patient; in fact, it may be ethically wrong to maintain a brain dead person on life support (unless they are awaiting organ donation). So what is brain death? Brain death is a state in which a person has no clinically measurable neurologic function. This requires the brainstem to be completely lost. The patient should have no pupillary, corneal, oculovestibular, or gag reflexes. They should be apneic (no breathing) and have no response to painful stimuli. They should not be on neuromuscular blockers or sedatives; their temperature should be normal. Sometimes an EEG is taken to document lack of brain activity (this criterion varies by state). There have been no cases of a person meeting brain death criteria later regaining consciousness. They can donate organs.

On the other hand, a person in a persistent vegetative state can appear awake. They may open their eyes, make movements, and demonstrate sleep-wake cycles. However, they are unconscious and unaware; there is no sign they can respond to outside stimuli. There are extremely rare cases of patients in persistent vegetative states that later regain consciousness. For this reason, these patients are not dead and it would be unethical for a physician to withdraw life support without consent.

Hoity Toity

I was amused by that phrase, "Hoity Toity," a description of a semi-formal end-of-year event we had. The "Food Appreciation Club" and the UCSF Chamber Music group (both started by and composed of first year medical students) teamed up to put on a really beautiful performance with yummy finger foods. It was good to see everyone dressed up and great to hear the fantastic talent in our class - Katie's singing, Jenny's piano, and Paul, Albert, and Elaine on violin among others. I enjoy chamber music; it has a different texture than large ensembles and the repertoire is pretty fun. It was a good way to end the year.

Unusual Psychiatric Disorders

There are some pretty fascinating psychiatric disorders that demonstrate the wide range of mental illness. When I first saw the title of a lecture on "abnormal illness-affirming behaviors," I didn't know what to expect. What does that even mean? Somatoform disorders are odd disorders in which patients have unexplainable physical symptoms. A patient might present with pain, tingling, and nausea but medical workup simply doesn't reveal anything wrong with the person. Some subtypes of somatoform disorders include conversion disorder, mass hysteria, and hypochondriasis. One extreme one, somatization or Briquet's disorder, requires 4 inexplicable different types of pain, 2 GI problems, 1 reproductive problem, and 1 neurologic symptom. In these disorders, patients aren't pretending they have illness; they really do have symptoms, and that makes it so much weirder and interesting.

In factitious disorders, patients self-induce or make up symptoms in order to "fake" being sick. Patients with disorders like Munchausen syndrome and Munchausen's by proxy like playing the "sick" role and getting medical attention. Yet the patient might not be conscious they are doing it. Quite odd when everyone else does their best to avoid doctors. This is in contrast to malingering where someone purposely and consciously fakes symptoms in order for secondary gain like getting out of work or getting a handicap sticker. Malingering is not a psychiatric illness (though it is something doctors have to deal with).

Lastly, we talked a little bit about personality disorders, a blurry subject due to the wide range of personalities and cultures that exist. Some odd or eccentric patients have paranoid or schizoid personalities while others are dramatic with borderline or narcissistic personalities while yet others act anxious and are avoidant or dependent. It's important for all physicians to learn how to identify these patients, work with them, and care for them. While I am unlikely to go into psychiatry, all of this stuff on human nature and the diversity of normal and abnormal is fun to learn.

Electroconvulsive Therapy

A psychiatric treatment for intractable severe depression is electroconvulsive shock therapy. I think when I came into the class, I had as much knowledge as (or less than) the general public about electroshock therapy. It sounds scary, brutal, and unscientific. By applying a strong electrical voltage at the temples of a patient, a grand mal seizure is induced. I get visions of "One Flew Over a Cuckoo's Nest" (which, incidentally, was filmed at a VA that I volunteered in) with sadistic administrators trying to control crazy patients. But that's not the case at all. Electroshock therapy is something that takes 10 minutes, is supervised by physicians, and has a remarkable response rate for grave depression. It works better than medications (but has a high relapse rate). And though no one knows how it works, it seems to be benign and has no contraindications (not even pregnancy). Pretty interesting.

Dali

For some reason, in thinking about and studying hallucinations and delusions, I thought of the art of Salvador Dali. "The Persistence of Time" (1931) is hauntingly beautiful and curiously bizarre. I really can't interpret or say much about it, but it's so mesmerizing.

Source: Wikipedia.

Quotable Quotes

"Magicians pull rabbits out of hats. Research psychologists pull habits out of rats."

Cadaver Memorial Service

Last week, we had a cadaver memorial service to honor those who donated their bodies for our education. It's really a monumental gift, one that is absolutely necessary for learning medicine. I've written about this before, so I won't say much more than I am very grateful and very admiring.

The service was an hour long and everyone (including schools of dentistry, nursing, and pharmacy) was invited to submit poems, reflections, or artwork. I wrote a poem for the occasion. This is a poem about departure.

-

Orison

The nicest receptions are the awkward ones
before the most serious of ceremonies.
This, in particular, was the immortal congregation
where Pluto was to be excommunicated
from this celestial council.
We never really noticed him, the other planets whispered.
Neptune said, I once saw him pass, eccentric,
but he didn’t say anything.
Wasn’t he just a rock too cold to socialize?
Too weak to fight off the pitchfork physicists
seeking to dethrone and tame him?

Holding a plate of pomegranate and the stem of a flute,
I gaze at the portrait of Pluto, looking past the icy exterior
and poorly defined surface details. For wasn’t Pluto
also sometimes a dog? Sometimes a God?
Sometimes an element found in nuclear bombs.
Is losing your planethood really losing everything?
I ask.
You catch me malingering into the night,
fabricating stories of this man whose exterior we have
only begun to know, whose interior we have only
begun to infer.

He leaves tomorrow for a light year cruise,
ironic because he was once the gatekeeper for the place he’s going.
Now he cannot wait to cloister himself with Persephone,
and in front of the gathered planets, he recites a poem:

Run, star princess, run with me,
satchel in hand, let us go to the sea,
stare upon the waves, those starry starry waves
that, moonlit coerced, reflect those graves
so wet with temptation, that in the gloomy dusk
we shell out the cocoon, shed the husk.
You look into the water, rippled and pine
as I trace your image, finger running a line
that parts the sea, so walk with me
out of those stone walls, the entropy.
Sleep, star princess, sleep with me,
constellation made from a plea,
hand in hand, we sink together,
as the satchel releases the worldly tether.

FPC Closure

For our "final" in FPC, we had an "Objective Structured Clinical Exam" (OSCE). It's one of those odd exams to test our patient interaction skills. There were three stations. In one, we conducted a focused exam on a patient with a particular finding. I had to do a cardiovascular exam, calculating jugular venous pressure, describing the character of a murmur, and checking for edema. At the second station, we interviewed and examined a standardized patient in pairs, then came up with leading diagnoses. Finally, as a whole FPC group, we worked through a paper case. I really like our group. This week we had our last FPC meeting at a cafe; it was really fun and we got our facilitators nice gifts.

Speaking of cases, I really enjoy them. In small groups for BMB, we've been getting pretty interesting patient scenarios and generating lists of possible etiologies as random and diverse as Lyme disease, psychosomatic disorders, neurosyphilis, multiple sclerosis, and bipolar disease. Then we order a certain number of tests to narrow down our differential. Finally, we decide how to treat the patient and, like "Choose Your Own Adventure," the different choices lead to different outcomes. It's fun.

Alcoholics Anonymous

One of our assignments to understand substance abuse and rehabilitation was to attend an Alcoholics Anonymous meeting. It was a worthwhile assignment. I wouldn't normally go to a meeting, but I didn't mind attending. The demographics were interesting; it was an open meeting of about 30 alcoholics, mostly men. The men sat apart from each other; the women sat with someone else. I was curious to find out that there were so many ritual-like components of the meeting. Whenever someone would introduce himself, there would be this autonomic "Hi, my name is ____. I'm an alcoholic." When people recited the 12 steps or quoted different parts of the handbook, it really seemed like they were all indoctrinated into this secret society with a code and handshake. There was a Lord's Prayer at the end of the meeting. All of this made AA seem like a religious institution whose first step of induction requires acknowledging a Higher Power. Kind of fascinating, though I admit this was my only experience so it may be skewed. AA gives attendees a sense of community; many seemed to be regulars. They struck up a pretty good debate about how to stay sober. One guy shared his life story. And I learned something.

Neuropathic Pain

Neuropathic pain is both interesting and horrible. It's different than ordinary pain in that it involves nerve damage. It doesn't respond well to usual pain medications like NSAIDs or opiates. Weird stuff like antidepressants are used to treat it. Trigeminal neuralgia, which causes high intensity high frequency shock-like pulses in the face, is considered one of the most painful conditions and labeled the suicide disease (Wikipedia) because people simply cannot stand the pain, and medications are inadequate.

There have been a lot of fascinating therapies developed for pain. We talked about ideas as diverse as acupuncture, hypnosis, placebo, deep brain electrical stimulation. Now what's interesting is that opioids (like morphine) are blocked by the pharmacologic antagonist naloxone (narcan). But, the pain relief effects of placebo and acupuncture are also blocked by naloxone, even though there are no exogenous opiates administered. The hypothesis is that these placebo-type interventions cause release of endogenous opioids, which is what relieves pain. I never really realized that placebo drugs have a physiologic effect; it really demonstrates how mind influences body. Oddly enough, hypnosis is not blocked by naloxone, and the hypothesis of how that works has to do with decreasing the emotional content in pain. If you're thinking about how much something is going to hurt, it's going to hurt. But the same stimulus might hurt less if the patient is hypnotized.

Rorty

I just read that Richard Rorty passed away a few days ago. I never took a class from him, but he was the stuff of legend. He was a philosopher, but professor emeritus of comparative literature (and only of philosophy by courtesy). Rumor has it this was because his work tried to undermine analytic philosophy, and analytic philosophers (which make up departments of philosophy) were so infuriated they wouldn't let him join the department. He argued (and I concede I have never read his major works) that we cannot faithfully represent a mind-independent external reality. This really hamstrings epistemology (the scope and nature of belief and knowledge). He argued that the truth of propositions has nothing to do with their correspondence to facts; meaning and truth are purely socio-linguistic products. Something is "true" because its truth works in our society, not because it is "objectively" true. This has huge implications about philosophy and science; we can never describe the fundamental nature of the world, and it would be incorrect to think that our philosophical and scientific theories do so. I happen to think Rorty is simply mistaken, but philosophy is built on intellectual debate. He, Wittgenstein, Kuhn, and a host of other great thinkers have really helped me figure out what I think about truth, science, and analytic thinking.

Zweifachers

The zweifacher is a Bavarian (German) dance that alternates waltz steps (in 3) with pivots (in 2). It's lots of fun because it's intensely dizzy. Now I know why (sort of). The semicircular canals in your ears which sense angular rotation are stimulated by changes in acceleration. Because a waltz or a merry-go-round or spinning in a chair has constant angular velocity, eventually the vestibular system will accommodate to the motion, making it less dizzy. But in the case of zweifachers, alternating waltzes and pivots causes an angular acceleration (or deceleration), leading to increased dizziness.

30 Years of Radiology

This is a CT of the brain from 1976. I'm not even sure what I'm supposed to see in this picture. Isn't it crazy how much imaging has improved in the last three decades? (Just google image brain CT).

Thoughts

How do you approach inevitability? How do you confront the thought that every "Once Upon a Time" must and will tumble to the simple two words "The End"? That every high-pitched baby's cry will be paired, equal and opposite, with the man's last gasp some dozens of years later? The closer we get to the doorstep, the more we beg time for another chance, the harder we cry, the more we try to grab at the confetti falling among us, knowing we cannot hold onto everything but trying nevertheless. We want an encore, we need a last dance. Is this not the curse of knowing you will fall to some disease? A Huntington-positive gene, a diagnosis of cancer, a baby with Ondine's curse? We will all depart sometime, somewhere, but it seems all so much more tragic when we can tell exactly when and how we will leave. If you have not experienced this dread of impending departure, I hope you never do.

I wrote something last year when I hardly understood the gravity of rhetoric and the opposite of fate: "In a blink, a heartbeat, it'll all be over, dust in the air, words pluming from my mouth, hyperventilating incoherence. A word, two, a hundred, a thousand - but even photographs are futile attempts to stop this magnificent mane-throwing beast, charging one-way and never looking back. When you draw optics ray diagrams in physics, you see that the beams converge and diverge, each following its own self-illuminated path. Here we come, focused, interlocking, hands reaching out. Can I grasp yours? Will you hold on? Will I swing you around, Texas Tommy, or latch onto your shoulders, Atlas of the blue cap? Is my influence so great? Are my crutches so weary? And yet, I ask these questions knowing far too well that the interwoven strands of Fate gaze down upon us, intolerable and reminding. How far can these manacles extend? How tight are the knots of this rope? Will I succumb to the fear that I shall be cast away an empty shell, a satellite orbiting the past, letting gravity like wine seep through my fingers as I try to find meaning and place in this beautiful, lonely world?"

Congratulations. I defer to the unyielding mistress of time. Goodbye.

Patient Presentations

The wonderful thing about BMB is the numerous patient presentations. It is incredibly valuable to see patients, hear them talk about their disorders, and ask them how it has affected their lives. It's not hard to learn about chest pain or difficulty breathing or yellow jaundiced eyes; these are symptoms and signs that we've experienced or we can imagine. But what about someone with bipolar disease? Suicidality? Who hears voices? These disorders in the realm of psychiatry justify their intrigue because we simply don't know what it's like to have that condition. The textbook criteria tell us very little about how these illnesses affect their family, their goals, even their everyday activities. Patient presentations in this block add a whole new dimension to my understanding of the mind.

We've had a few patients come in to talk about their experience with different neurologic diseases. A woman with a congenital dystrophy talked about how she was unable to run her entire life and is now nearly bound to a wheelchair. A man discussed how he is able to be a high-functioning lawyer despite multiple sclerosis. Two great old men who had experienced strokes entertained us with humor and hope as they described how they became best friends at the stroke rehabilitation facility. They bantered, joked around, and really got us to laugh.

We've also seen several patients struggling with psychiatric disorders. A woman with "double depression" (dysthymia plus major depressive disorder), a patient with bipolar disease, a man who jumped off Golden Gate Bridge in a suicide attempt. Only about 20 of the 1500+ people who've attempted suicide off the bridge have survived, and he was one of them. Just today, we had a patient with a borderline personality disorder and another with Huntington's disease.

Honoring patient privacy, I won't elaborate on any individual stories. But I've learned an incredible amount from these brave and fantastic people. Illnesses don't characterize them. They are characterized by an indomitable spirit facing adversity we cannot even imagine. They stride into the classroom, enrapture us with their tale of ongoing struggle with a chronic disease. They teach us, they cry with us, they laugh with us, and they remind us why we chose to become physicians.

Oddly Enough

Today's New England Journal of Medicine (NEJM) has a Correspondence article on "Acute Wiiitis." I had to count my i's when I typed that. Apparently, a resident woke with intense pain in the right shoulder: acute tendonitis of the right infraspinatus. This was not tennis elbow. Instead, the resident had been playing tennis on a Nintendo Wii. I was quite amused that the article describes the Wii remote ("Wiimote") in quite a bit of detail ("14.5 cm by 3.0 cm by 3.0 cm, with a weight of approximately 200 g"). The final diagnosis was a subtype of "Nintendinitis," appropriately named "Wiiitis." The treatment (though there haven't been any case-control studies demonstrating its effectiveness) was ibuprofen 1 week and no more Wii. After considering the multitude of different video games for this system, the article concludes, "Physicians should be aware that there may be multiple, possibly puzzling presentations of Wiiitis."

And you thought it was hard to get published in NEJM.

http://content.nejm.org/cgi/content/extract/356/23/2431

Emergence

Emergence is a fascinating philosophical notion that has been applied to an incredibly diverse array of concepts, from artificial intelligence to hurricanes to theory of mind. In fact, I learned about emergence from reading a philosophy paper describing baseball. Emergence refers to the way new phenomena can arise from simple interactions between many players. There are many individual people on a baseball team: the shortstop, the pitcher, the right outfielder. None of those people, individually, demonstrates "teamwork." You don't say, "Wow, that catcher has teamwork." But you take all these individual people and have them interact, and sometimes, you can get the property of "teamwork" to emerge. A strong view of emergence means that systems have properties that are irreducible to the system's constituents. Something new comes out; the whole is more than the sum of its parts.

"Although strong emergence is logically possible, it is uncomfortably like magic. How does an irreducible but supervenient downward causal power arise, since by definition it cannot be due to the aggregation of the micro-level potentialities? Such causal powers would be quite unlike anything within our scientific ken" (Mark Bedau).

I believe strong emergence may explain a lot of scientific phenomena. A single neuron can't "think." It's just made up of cell membrane and mitochondria and sodium channels. It fires all-or-nothing action potentials. It's pretty dumb. But you take a few of them and have them interact. They can start to do cool things, modulating each other's signals, affecting each other's growth. Wikipedia says there are anywhere from 100 billion to 100 trillion synapses. Maybe - just maybe - that's enough to create these unbelievably remarkable properties "thinking" and "consciousness." These higher level functions somehow result from the interactions of all the neurons, though no individual cell has such properties.

I've spent a considerable amount of time thinking about this topic. It has become the mainstay for explaining a ridiculous number of things, from how ant colonies work to architecture to friction. It seems like a simple idea, yet it has fundamental implications about science. If certain properties of a system emerge from complex interactions of its constituents, then "reductionist" science of breaking down problems into its parts will give little insight into the emergent properties. Indeed, in the last decade or so, there has been a great interest in "systems biology" because of this.

References: Wikipedia.

Back

I'm back and slowly recharging. While I was studying for the exam, I got to thinking that we know so little about "fuzzy" neuroscience (though I can't really say why I call it that). For example, what neural circuits or neurotransmitters or anatomic structures play a role in things so diverse and wonderful as emotion, behavior, memory, or language? These abilities really make us us. They're central to our identities as human beings. Yet it seems grossly inaccurate and imprecise to say emotion is housed in the amygdala or language is defined by the connection between Broca's area and Wernicke's area. Lesion studies and, more recently, function studies like fMRI certainly implicate these parts of the brain in these multifaceted tasks. But the story is far more complicated than these approximations suggest. Sure, for an exam, we memorize that the frontal lobe has something to do with behavior. But what? And how? Tomorrow, I'll really get back to blogging, and I'll start with the philosophical idea of emergence.