Stanley William Hayter

"Combat" by Stanley William Hayter, 1936.

Hayter trained as a chemist and geologist before pursuing art, eventually founding Atelier 17 in Paris and working with Jackson Pollock and Mark Rothko (among many others.)

The Future of Medicine?

Sorry it's been a while -- but with the musculoskeletal final safely behind me I can turn to RMV again...

One question that occasionally passes through my mind is "What is medicine going to look like 30 years from now?" In my 50's, I'll probably be at about the highest arc of my career, but will that career be recognizable? After all, scientific progress proceeds exponentially -- in the 2040's, the present era will probably seem just as quaint as the 1890's do now. Many older physicians tell me that a great deal of what they learned in medical school is obsolete, a trend that has no sign of fading.

What brought this to mind was an article in Wired magazine (sorry, not online yet) about the Archimedes organization, whose goal is to produce a computer program that can quantitatively model the human body, completely. Quite an ambitious project, considering the untold intricacies of human physiology -- here is a chart that shows JUST the metabolic reactions! If successful, this would be a holy grail for medicine. Every drug's effect could be simulated before touching a human. Combined with genetic information, treatment algorithms could be personalized for each individual. Already, the designers have used their system to predict the outcomes of major randomized drug trials, successfully.

I personally think this was a great thing, but the article was not as positive. Will a computer take over the role of a physician? I doubt it. Physicians have always use tools, tests, and rubrics; this will just be a very powerful one. A human being is still the most adaptable and easily programmable computer we have, and physicians will always be needed to interpret for patients the results their science gives them. The doctor of the future will probably need to know much more about statistics then they are currently asked to -- the spheres of epidemiology, computer science, and individual medicine are rapidly colliding.

Cool Stuff on Them Interwebs

OK, this is a lazy post.

Popular Science's Most Amazing Medical Images.
Some of these are cheesy, others touching, and others very, very cool.

This is pretty cool just from an experimental setup standpoint. I briefly worked in a neuroscience lab where we had mastered how to image clusters of neurons in genetically engineered mice -- every time the neuron was activated, it fluoresced, and we could see local-scale firing patterns. The problem was being able to do this while the mice ran in mazes, etc. We used fiber optics, but they would often either pull the tube out of their heads or push it further in and kill themselves. This solution reminds me of the "locomotion compensator," invented by Ernst Kramer and Peter Heinecke in the 70's to track insect movement. (Can't find the original article but here are articles that cite it.) Insert joke here about "reinventing the sphere."

The Sabotuer

(A response to Adrienne's post and this article.)

Excerpts from the diary of Holger Nielsen

LHC construction day 197

Setbacks again! The external heatsink pumps are fried. Turns out they were put in backwards. ($10 million oopsy!) Ninomiya swore that he checked them, but he's been so clumsy lately. Too clumsy. I'm a bit suspicious.

LHC construction day 210

It does't even surprise me anymore when the flexor coils fail. Except this time, we found something really weird--a monogramed handkerchief, right between the 3rd and 4th layers! "H.B." was all it said. Hank Binslow was promptly fired. Find the problem and fix it; that's my motto.

LHC construction day 234

Reviewing the schematics in my living room last night, I had the eery sensation of someone watching me from the window. I didn't see anyone when I turned around, but then I heard a car screech away from the curb. Stuck to my front door with a Bowie knife was a note. "STOP THE PROJECT -- HIGGS."

LHC construction day 275

When I got to my computer today, I noticed that someone was still logged into FaceBook: "Higgs.Boson@particles.com. Birthday: July 2, 2011. Interests: homemade pasta, photography, creating black holes (J/K GUYS, LOL!)" Also, my entire hard drive was erased.

Santiago Ramon y Cajal

I have a folder of "heros" in my browser bookmarks, people whose life stories remind me that truly anything is possible for an individual. One of them came up this week in our primer to neuroanatomy: Santiago Ramon y Cajal. He was an amazing turn-of-the-century scientist who greatly advanced our knowledge of cerebral microarchitecture. An artist as well as a neuroanatomist, he carefully sketched hundreds of neurons before making a detailed depiction of the "archetypal" neuron of that type. Like many great scientists, he was precocious and bull-headed--my favorite story about his life is that he destroyed the gates of his small Spanish town with a homemade cannon at age 11.

Among numerous scientific articles and textbooks, he also wrote a short book called "Advice for a Young Investigator". The title seems to be a rip off of Rilke, but that was a later publisher's creation. The original title translates directly as "Precepts and Counsels in Scientific Investigation: Stimulants of the Spirit"... a bit unwieldy. However, the book really can be seen as the scientific version of Rilke's "Letters to a Young Poet": it is the sage advice of a elder practitioner on how to navigate an emotionally taxing profession. Some of it is a bit outdated; one section includes advice on how to pick the appropriate scientist's wife. It also has an interesting chapter on "Diseases of the Will", cataloging the various personality types that will fail at science: the megalomaniacs, the overly fastidious, etc. (Read it and see who comes to mind...) However, most of it is very wise, ("because science relentlessly differentiates, the minutiae of today often become the important principles of tomorrow") and occasionally it is very beautiful and inspiring: "I believe that all outstanding work, in art as well as in science, results from immense zeal applied to a great idea." Recommended reading for scientists young and old.

Politely Stabbing Grandpa

My inner boy scout came out today as I voluntarily gave flu shots at the university's geriatric center. When the organizers were asking around a couple weeks ago, I said yes right away -- because the idea scared me. I've been cutting and chiseling a cadaver for weeks now, but sticking a needle into a live person? Now that's bizarre. Yet by noon today, I had already given about two dozen flu shots.

The shot itself was easy. Sure, I had to be careful not to go too far into the muscle, a little tricky on some the frailer patients. But the needles were so small and sharp, and automatically retractable, that technically there was almost no problem at all. Talking with the elderly, however, was much harder. Some of them were a little grumpy and just wanted to get out of there. Some were happy to be there, but very hard of hearing. More subtly, though, were the little differences in customs and mannerisms. How do the elderly want health providers to dress? What greeting and level of conversation do they expect? What makes them comfortable? I also noticed that some made strange (yet well-meaning) comments about my female and minority colleagues (for example, asking the Chinese student from Detroit if "you're doing this because your culture values your elders.") You could almost compare our interactions to time-travel; I get to navigate the social terrain of 50-odd years ago.

It was a good experience, perhaps because it made me feel more like someone training to be a doctor and less like a molecule memorization machine. Also, it was good as a quick trainer for personal skills. The instructors here constantly emphasize how important they are. As a doctor, someone you have never met before will walk into your room, and within one minute has to feel comfortable getting a needle, or talking about drug use, or showing you their genitals. Failure to build that trust can lead to real medical problems, if people feel too hesitant to share some vital piece of information with you. I've got a lot to learn...

The Mollusk

Couldn't think of any medical thing to write about this week, so thought I'd write about some of my other favorite things: art and surfing. These two are nowhere more beautifully combined than in The Mollusk, my favorite surf shop in the world. If you are in San Francisco I strongly recommend checking it out. I think they have shops in Venice CA and New York also, but SF is the original as far as I know.

The Mollusk is so refreshing in its aesthetic treatment of surfing. Most popular glossy surfer mags are a battlefield of images and advertising, each trying to outdo each other with neon, lightning bolts, and over-the-top, in-your-face, Red-Bull macho aggressiveness. Maybe it's a NorCal/SoCal thing, but the Mollusk seems to take a more mello attitude towards their art, dress, and probably the way they surf. While glossy mag surfers get their boards from the mass-produced epoxy bargain warehouse, your typical Mollusk surfer probably made their own board, a single fin fish or even an alaia. Glossy mag surfers wear electric yellow rash guards and punch out locals at the most crowded spot on the beach, while Mollusk surfers probably keep a secret spot up on the Humboldt coast for naked sessions by full-moonlight. Whether it's shortboards or logs, local break or foreign trek, the Mollusk emphasize everything I love about surfing culture--grace, relaxation, beauty, and humor (SEA KAT!).

I'll through a few shoutouts to the artists and bloggers associated with that crowd, so you can see for yourself what I mean:
Thomas Campbell (go see The Present if you can)
Serena Mitnik-Miller
Ryan Tatar
Hydrodynamica
Nate Russell
Andy Davis

Screened

Like millions of other students around the country, I was required to get a screening test for tuberculosis before starting school this month. I went to the corner family health clinic, got my injection, and came back a couple of days later. Unlike many other students, my test was positive. I couldn’t believe it—my hand was visibly shaking as we discussed the results. Would I be allowed in the school? Would I even be allowed near the other students? The nurse reading the test just laughed and told me not to worry; most medical students have been exposed to TB by their first year in the clinic, so I’ll just have a head start on the class. Just to be sure I didn’t have an active infection, however, she signed me up for a chest X-ray.

You’ve probably had one of these skin tests before. Often called a PPD test for purified protein derivative, the provider injects a droplet of fluid containing tuberculin bacteria proteins between the layers of your skin. When you return two days later, the clinic checks to see the degree of immune response your body has mounted against the foreign material. Usually, the spot is red for a few hours and then fades away: your body does not consider the proteins threatening. But if the spot remains raised, it means your immune system has responded more aggressively and in all likelihood has seen live tuberculosis bacilli before.

The chest X-ray showed no visible lesions in my lungs. For now, the best interpretation was that I had only a latent infection and was not contagious. Still, my lifetime risk of developing active TB was 10% unless I took a long course of anti-tuberculosis medications. “When could this have happened?” I wondered. A moment’s reflection provided some answers: I had spent all of last year working in a large hospital, and I had recently traveled in South East Asia, including some very rural areas. I could have easily been exposed in either of those places without realizing it, carrying a small colony of tuberculosis bacteria in my body unawares.

As a health minded medical student, I decided I must absolutely begin the anti-TB drug Isoniazid as soon as possible. It looked promising—finishing the course would reduce my lifetime risk of active TB from 10% to less than 1%. But the drug was not easy. I would have to take a pill every day for the next nine months. I would have some risk of neuropathy and anemia, but most certainly of liver damage, requiring a long hiatus from my enjoyment of craft beers (unthinkable!).

Still, it was necessary. Before starting the drug, however, they wanted to do one more test to make sure I really had TB, a test with much higher specificity. The “QuantiFERON-TB Gold” test required a small amount of my blood, which they mixed with TB proteins (similar to the ones injected into me earlier). If my white blood cells released lots of interferon (an immune attack signal) in response to the proteins, then I had indeed been exposed to TB.

Fortunately, they didn’t. A single phone call from the clinic made my year—I didn’t have TB! After I finished dancing in my living room, I was left with a list of questions: How could the two tests be different? What if I had taken the drug and had liver damage? Why even give PPD tests at all?

I had my brush with a false-positive, one of the reasons we don’t screen everyone for everything. Something non-intuitive and often surprising is that the accuracy of a test depends just as much on the population it is given to as on the characteristics of the test itself. For example, suppose a test with 99% sensitivity (ability to catch disease carriers) and 99% specificity (ability to identify people without the disease) is given to a population of 10,000 where 100 people have the disease (1% prevalence). Even with such an amazingly good test, only half of the people with a positive result would actually have the disease! This problem will always happen when a screening test is given to a population with a low prevalence. Test results don’t define your chance of having a disease, they adjust your risk based on the chances you came in with. This was very poorly understood by Illinois’ Gov. James Thompson in 1987, who enacted a law requiring HIV testing of all couples applying for a marriage license. Since heterosexual, monogamous couples were probably the lowest risk group besides cloistered clergy, even with a near perfect test there would still be an egregiously high number of false-positives. Indeed, there were, and most couples went out of state to marry until the law was repealed in 1989.

Even when good tests are available, expense is also a consideration. The PPD test is the mass screening test not because it is the most accurate, but because it is the cheapest. Since the main risk in the beginning is missing people who actually have the disease, the guidelines are set up so that nearly everyone who has the disease will have a positive test, plus a few people that don’t have the disease as well (a sensitive test). Only after the initial screening do we use the more expensive and more specific interferon test to knock out those false-positives who definitely don’t have the disease. Interestingly, it’s hard to tell what the actually accuracy of the different TB tests are, since there is no gold-standard (a supposed perfect test) with which to compare them to. A study used cross comparison statistics to try to find an answer, and you’ll see it’s nowhere close to our hypothetical example.

So, should we even continue giving TB screening tests to students, given that they are such a low-risk population in general? Once all the bad results are sorted out, the bottom line is that the TB test is useful because we can do something about the results—effective treatments are available. The clinical utility of a test is even more important than the accuracy when deciding on a screening program. There is a near perfect test available for Huntington’s disease, but 95% of at-risk people choose not to get it, since there is no treatment for the fatal illness. In the middle of all these questions is the debate over prostate cancer screening by PSA, in gray areas both for accuracy and clinical utility. 23andMe will scan my genome for markers associated with heart disease and diabetes, but could I really use the information that my lifetime risk is 9% instead of 7%?

First Post

Medicine is a science of uncertainty and an art of probability.
- William Osler (1849–1919)

TO any one reading this...

Thanks for coming back to check out the first post of Results May Vary. Fitting to its name, I'm sure this journal will transform and metamorphose along with my varying interests, studies, and fancies over the ensuing years. Its essence and purpose, however, is to serve as captain's log through the uncharted waters of medical school and beyond. Three weeks into my first year, I'm already absorbing more knowledge more quickly than I ever thought I could. Cell cycle regulators, transcription factors, enzymes that add phosphates and those that remove them, cascades of signaling proteins with one arrow leading to another and another and another... until the last arrow points to a question mark. We've reached the end. The limit of knowledge. But I think, for a young doctor, that therein lies the secret: how you manage the unknown is much more important than how you mange the known--because patients rarely hand you multiple choice lists. To that idea, then, this series is dedicated; and I hope you'll join me as I continue to explore the vast world around me, and figure out how very little I really know.

Chris