Med Student's t-Test

campus posters

2009-10-18T07:28:00.001-07:00

Penny wise, pound foolish

2009-03-16T06:48:00.000-07:00

I picked up a Poland Spring water bottle at an event on campus. The label was much narrower than usual. Half of the label was taken up by text crowing about how many trees Poland Spring was saving by shrinking its label.

Children are dying of cholera in Zimbabwe while we Americans have unlimited access to free water of exceptional quality, and when we purchase water bottled in plastic and driven by truck hundreds of miles we congratulate ourselves on how "green" the label is.

Brilliant.

Hard to focus on labwork

2009-02-23T17:30:00.000-08:00

1) Yay, new readers! Thanks for the linkage, SBM. I just noticed them, but I look forward to reading the comments.

2) The same naturopath who visited last year came to campus, and his presentation was identical. Details on it later. In short, it was still crappy.

I've just listened again to a podcast episode featuring a Chicago-school economist soul searching over whether he's just as ideological as the Keynesians and how statistical analysis can be twisted to support any bias. I'm not terribly sophisticated in economics, but I recommend the episode if you care about how we know and why we feel certain. The lessons are obviously generalizable to contentious issues in any discipline. Of course, today it made me think about alternative medicine.

I confess, I feel quite confident about certain opinions I have regarding alt med, probably more confident than is strictly appropriate given my scholarship and experience. To be blunt, I basically agree with most of what Steve Novella tells me, and I revel in being part of the skeptical "in-group" of truth seekers. Now, I feel I can justify trusting him because I understand and approve of how he searches for answers, and I really would bet money that I am closer to right than the CAM advocates at school. But of course, they must feel the same way about their opinions and the role models that inspire them! Brian Dunning made this point well recently on Skeptoid. Some humility, or at least empathy, is in order to maintain respectful dialog and keep myself open to the possibility that new information could dramatically change my mind.

Later today I had an experience that drove home these thoughts. Seeing a recent post on SBM about naturopathy, I chimed in with a glib summary of how silly I found today's naturopath. A fellow reader misinterpreted my brief comment and ripped into me for underestimating the absurdity of naturopathy. (On re-reading, he wasn't that harsh. I guess I just saw red when he accused me of being a shruggie. If you're reading, Joe: no hard feelings!) The format of semi-anonyous posting on websites definitely lends itself to sharp lines drawn between groups, and vitriol against "the others" is the clearest proof of membership. I'm not the first person, of course, to note how lack of body language, eye contact, and context make online conversations fraught. But the exchange made me reflect on the dangers of assimilating too fully into any group identity; even a group dedicated to "rationality" could experience herd mentality. If organizing skeptics is ever not like herding cats, then something has gone terribly wrong!

More on the naturopath when I have enough time to write. I'd better get back to my microscope...

Lies, Damned Lies, and CAM Statistics

2009-01-19T21:27:00.000-08:00

My latest submission to the campus newspaper:

Do 4 in 10 of us use CAM?
Sure, if you count vegetarians and Pilates

Flipping through an old [university] magazine in a waiting room, I read [faculty member's] assertion that complimentary and alternative medicine (CAM) should be studied because over 30% of Americans use it. In the Wall Street Journal on 12/26/08, journalist Steve Salerno cited a recent report of 38% CAM usage, although he used the figure in a compelling argument against spending public dollars on non-scientific modalities. Salerno received a response in the 1/09/09 WSJ by a quartet of CAM's finest that used bizarre logic: any lifestyle change (e.g., diet, exercise, stress management) that prevents disease is CAM, lifestyle change is an inexpensive way to prevent chronic disease, therefore we need "serious government funding" of all CAM (including chi manipulation). Physician bloggers from Science Based Medicine call this tactic "the CAM bait-and-switch," and it involves the same conflation responsible for the claim that 4 in 10 Americans use CAM.

Look at the data behind the "4 in 10" claim that Salerno cites. In a 2007 survey (raw data here) of 30,000 households, the most frequently reported use of CAM in the past year was of "nonvitamin, nonmineral, natural products" (17.7% of respondents), and the most common such product was "fish oil or omega 3 or DHA." The next highest rate was for "deep breathing exercises" (12.9%), and number three was meditation (9.6%). In fourth place was "chiropractic or osteopathic manipulation" (8.6%), the vast majority for back, neck, or joint pain. The next five most common responses were similarly unexciting: massage (8.3%, also mostly for back pain), yoga (6.1%), diets (3.6%, primarily vegetarian, Atkins, and South Beach), "progressive relaxation" (2.9%), and "guided imagery" (2.2%). Dude, where's my chi?

Homeopathy made the top ten with 1.8% of respondents. Acupuncture tied with Pilates at 1.4%. Ayurveda, Qi Gong, and Reiki altogether made up less than 1%.

The big CAM winners were the supplement industry, heavily marketed and poorly regulated thanks to its congressional lobbying, and manipulation/massage for musculoskeletal pain, which is not terribly "alternative." Disciples of CAM can claim a vast public mandate only by appropriating all nutrition, exercise, and relaxation techniques, which are thoroughly uncontroversial aspects of our curriculum. Although Deepak Chopra and Andrew Weil want us to believe that 4 in 10 Americans believe in CAM (incidentally, about the same fraction that denies human evolution), these data suggest a figure more like 4 in 100 for the really magical stuff.

Of course, neither proof of efficacy nor need for research should be a popularity contest. What really matters for any potential therapy are evidence and plausibility, hurdles that cannot be sidestepped by surveys or rhetoric. Each independent CAM modality must stand or fall on its own merits; accepting all CAM because massage feels good and some herbs are efficacious is as intellectually dishonest as rejecting all CAM because Kevin Trudeau is a fraud.

Proud to say I reached my conclusions on the survey before reading the thorough SBM analysis, though that blog pointed me to the CAM response. I was primed to be suspicious of such statistics thanks to a great podcast by Mark Crislip on a similar, older survey.

This is your Nature on drugs

2008-12-14T16:29:00.001-08:00

http://www.nature.com/nature/journal/vaop/ncurrent/full/456702a.html

In college I was once shocked to learn that an engineering classmate routinely took caffeine pills to fuel all-night coding sessions. Some years into medical school, after learning to love coffee, I found myself discouraging a friend from boosting his study efficiency with Adderall. A 12/07/08 commentary in Nature forces me to examine this aversion. Seven authors—experts in fields from law to neuroscience—call for policies supporting “responsible use” of cognitive-enhancing drugs by healthy adults.

Most of us would not deny cognitive-enhancing drugs to Alzheimer’s patients, but the Nature authors assert that such tools should be accessible to all adults, within safety limits. A cognitive-enhancing drug, they argue, is fundamentally no different from cognitive-enhancing activities like sleep, exercise, nutrition, and Kaplan review courses. They stress the need for research programs and policies that promote evidence-based evaluation of the risks and benefits of cognitive enhancements, particularly unknown long-term effects on memory or personality. Current regulations and social norms, however, have set up inconsistent barriers to use of and research on mind-altering substances. Caffeine and nicotine are cheaply available, Ritalin and Modafinil require prescriptions, and forget about cannabis! Although many restricted drugs are indeed too dangerous to be used freely---and like physique-enhancing steroids might rarely be appropriate for children even if rules change for adults---the Nature authors suggest that some resistance is based on puritanical or naturalistic notions that unhelpfully impede progress. Imagine if the first books were burned as "unnatural" memory aids or if Edison's light bulb was extinguished for fear it would raise expectations for human productivity.

We in medicine must address this issue, both personally and professionally. Medical students endure academic challenges that call for every aid possible, and likely many of us rely on cognitive-enhancing drugs to some extent. Sleep-deprived residents face an even starker need, with life-or-death consequences for themselves and patients. Should on-call doctors be given free (or compulsory) alertness drugs? Even if we survive training without pharmacological help, those of us in primary care and psychiatry will undoubtedly face patients eager for such drugs in absence of any disease. Let us have the discussion now so we will be prepared to respond thoughtfully as new drugs are developed and demand increases.

Elephant in the Room

2008-11-25T18:33:00.000-08:00

An ancient Indian fable tells of blind men disagreeing about the nature of a large object before them, because they fail to realize that they are touching different parts of an elephant. A scientist can be like the blind men in her narrow focus: the physicist sees the world as energy, the chemist talks about atoms, the biologist thinks in molecules, the sociologist focuses on organisms, the ecologist considers systems. Science works because countless investigators in many different fields are all studying different aspects of a single elephant named Nature, and our greatest educators are those who tie the disparate accounts into a cohesive narrative. The analogy works in patient care: the internist, the cardiologist, the surgeon, the anesthesiologist, the nurse, the physical therapist, the pharmacist...each of these players views the same patient through a different lens, focusing on particulars related to his specialty. Unlike the foolish blind men, however, health professionals rest easy with the knowledge that their superficially dissimilar fields are all ultimately based in empirical science. The same models of human physiology and pharmacology support each medical discipline, from nephrology to psychiatry. A big problem I have with "alternative medicine" is that it has no such elephant connecting its diverse claims.

First of all, alt.med lacks a good definition aside from "any ideas about health that are not accepted by most modern physicians." Some advocates use language that smacks of post-modernism or cultural relativism, which has no place in an empirical discipline like medicine. If you think "Western" physicians are "closed-minded" to ancient folk remedies, please take two Aspirin and call me in the morning. Modalities less ancient and foreign are also welcome into the potpourri of alt.med, with no prerequisites except failure of acceptance by scientific thinkers. Worshiping ancient philosophies and popular superstitions is no basis for a system of health care.

Secondly, am I the only one bothered by the fact that alt.med ideas conflict not only with accepted theories of reality but also with each other? Reiki, homeopathy, and acupuncture are laughable individually, but I cannot understand how one person can simultaneously advocate all three. Not only would my campus alt.med group encourage me to accept an "alternative" pharmacology that defies all chemistry, not only should I believe in "auras" that make a mockery of physics, but I am also asked to accept that ancient Chinese discoveries baffle anatomists to this day. Sorry, you crossed the line by disrespecting our anatomy profs.

The lack of discrimination required to embrace divergent alt.med claims reminds me of the title of a book by another type of true believer: The Psychic Sasquatch and their UFO Connection.

But surely, the alt.med agnostic implores me, no one is really saying that homeopathy cures all disease. Perhaps some diseases are treatable by balancing humors, some by manipulating auras, and others by unblocking chi. That is not what the believers suggest, I respond. The homeopath advocates using his sugar pills for any disease for which no "conventional" treatment exists. I equate such apologia with the scientifically bankrupt idea of Intelligent Design; your treatment of "last resort" is nothing more than a "god of the gaps." If its definition and theory cannot be formulated more precisely, then count me an alt.med atheist.

Professional codes of medical ethics clearly state that our actions should be guided by evidence when possible and scientific plausibility at all times. I fail to see how most of alt.med meets that standard. Certainly accepting it wholesale, as I seem to be asked to do by campus groups, is ethically and intellectually ruinous.

Forget the Flintstones: Disappointing Data on Vitamin Supplementation

2008-11-25T06:40:00.000-08:00

Physicians make decisions based on evidence when possible and on scientific plausibility when necessary. If a relevant randomized controlled trial (RCT) is not available, then a physician must choose whichever action most "makes sense" based on accepted theories and existing evidence. Eventually the lacking data is generated, allowing such choices to be vindicated or refuted with confidence. Recent reports in The Journal of the American Medical Association (JAMA) on vitamin supplementation for prevention of cardiovascular disease (CVD) illustrates this process.

Antioxidants have enjoyed an irrational exuberance in the marketplace, promoted in everything from pomegranate juice to ginger ale. The rationale seems sound: oxidative stress damages biological molecules, so antioxidants might protect against processes of aging, inflammation, neoplasia, neurodegeneration, and more. We know many benefits of a diet rich in antioxidant-containing fruits and vegetables, so similar effects for antioxidant supplementation are plausible. Sadly, many RCTs failed to show a meaningful effect, particularly for CVD (HOPE, WHS, HPS, HATS, ATBC). The most recent trial was the Physicians' Health Study II, which followed 14000 US male physicians aged 50+ for 10 years. Compared to placebo neither vitamin C nor E reduced the risk of major cardiovascular events, and E actually increased the risk of hemorrhagic stroke. The hypothesis failed badly.

Another longtime scientific suspicion is that B vitamins might prevent CVD by lowering homocysteine levels. A genetic defect in methionine metabolism results in both homocystinuria and early thrombotic disease. Animal models demonstrate plausible mechanisms for homocysteine-mediated vascular damage. Epidemiological data shows a correlation between blood level of homocysteine and risk of heart disease or stroke. The stage was set for conclusive proof, and large RCTs were planned. Trials have been mostly negative, however (VISP, HOPE, NORVIT, WENBIT), including the recent Women's Antioxidant and Folic Acid Cardiovascular Study, which found no effect for supplemental B6, B12, and folate in 5400 US female health professionals aged 42+, all with a history of CVD or multiple risk factors, followed for 7 years. The vitamin intervention clearly lowered homocysteine levels, but no difference was seen in cardiovascular events. Apparently this correlation did not imply causation.

As JAMA editorials indicate (vitamin E, homocysteine), many physicians are now concluding that these once-promising hypotheses are incorrect and that vitamin supplementation might actually provide more risk than benefit for some patients. Thankfully, we still have evidence-based tools for preventing CVD; a huge RCT was recently halted early because it found such terrific new results for statins (JUPITER). And for patients willing to make tough lifestyle changes, we can always recommend as smoking cessation, regular exercise, and a colorful diet.

Absurd Acupuncture Assertion

2008-11-21T20:37:00.000-08:00

The alt med group on campus recently invited an acupuncturist to speak. I did not attend because of another time commitment, but I knew that listening to a non-physician would be painful without insight. Thankfully a friend of mine went, with instructions from me to take notes on specific claims and supporting references.

The speaker claimed that acupuncture is better than morphine for controlling pain. My friend asked for a supporting reference. The speaker apparently flipped through slides searching before admitting he had none, but gave my friend his email address. Friend followed up, and he replied with the 96-page WHO review of acupunture (which, I was delighted to realize, was torn to shreds in a recent book I read). The speaker's numbers were found early in the article:

This publication reviews selected studies on controlled clinical trials. Some of these studies have provided incontrovertible scientific evidence that acupuncture is more successful than placebo treatments in certain conditions. For example, the proportion of chronic pain relieved by acupuncture is generally in the range 55–85%, which compares favourably with that of potent drugs (morphine helps in 70% of cases) and far outweighs the placebo effect (30–35%) (1–3).

"Incontrovertible scientific evidence"? I had to look up those three citations it gives.

1. Lewith GT et al. On the evaluation of the clinical effect of acupuncture. Pain, 1983, 16:111–127.
2. Pomeranz B. Acupuncture analgesia for chronic pain: brief survey of clinical trials. In: Pomeranz B, Stux G, eds. Scientific bases of acupuncture. Berlin/Heidelberg, Springer-Verlag, 1989: 197–199.
3. Richardson PH et al. Acupuncture for the treatment of pain — a review of evaluation research. Pain, 1986, 24:15–40.

Number 1 is a 1983 article that neither presented nor reviewed data. Rather, the authors instructed acupuncturists on how to design trials with appropriate controls, blinding, and sample sizes. Some recent trials were reviewed as examples of studies so poorly designed that they were a waste of time (e.g., power = 17% for alpha = 5%). Hardly support for the morphine claim!

Number 2 is a three-page chapter in a 1989 book about acupuncture. Lame.

Number 3 is a 1986 review of clinical trials. The range "55-85%" comes from this review's summary of clinical trials. It also mentions "30-35%" for placebo, but for that figure it cites the 1955 Beecher paper that originally defined "placebo" rather than using placebo responses from the reviewed trials, which, when they were reported, were generally higher than 35%. I have no idea where that 70% for morphine came from.

This is the speaker's idea of supporting a claim with data? A review that cites other reviews? From 22 years ago? At best, this is a case of intellectual laziness. At worst, it is dishonesty and deception. Good as morphine, my ass.

Naturopathetic

2008-11-21T20:25:00.000-08:00

Here is the essay I would have submitted to the student newspaper had the homeopath not visited campus right before it went to print:

"On [date], I attended an [alternative medicine group]-sponsored lecture by a naturopath entitled “Stress, Nutrition, and the GI Tract.” Later that week I enjoyed a research presentation by [school] Department of Surgery Chair [Surgeon], MD. Both lectures discussed intestinal injury, leakage of gut contents into the circulation, and subsequent systemic pathology. The contrasts, however, illustrated important differences between “alternative” and scientific medicine.

"Academic physicians understand that useful models of disease and treatment are focused. [Surgeon]’s hypothesis addressed acute sequelae of hemorrhagic shock: the sympathetic nervous response constricts gut arteries, causing transient intestinal ischemia, whose resolution causes reperfusion injury, which allows bacterial lipopolysaccharide to leak into the bloodstream, culminating in sepsis. The mechanism was complicated, but each step was testable. The naturopath also discussed stress-induced gut ischemia, but by “stress” he meant “anxiety” rather than “shock,” and he claimed that “stressful” lifestyles result in chronic intestinal ischemia. Furthermore, he said our guts are chronically inflamed due to numerous insults: “fried food, preservatives, sugar, chemicals, allergenic foods” as well as unspecified toxins and parasites. The resulting leaky gut is blamed for a wide range of symptoms and diseases, from cardiac to psychiatric; “whenever I see skin problems," the naturopath declared, "I treat the gut.” A common feature of alternative medicine is to explain many disparate diseases by a single mechanism, whether leaky gut or blocked chi.

"Even plausible mechanisms and treatments must be supported by evidence. [Surgeon] presented numerous slides of graphs and photos, data from years of experiments in his lab. He described results and questions from animal models, and he told of prospective, controlled human trials. Perhaps this naturopath was too young to boast PubMed citations, but since his theme was “naturopathic apologetics for treating the gut” he might have shown results from seminal work in his field. Instead, he flashed up some abstracts that were at best suggestive but mostly irrelevant. One of his favorites was a case study of a teenager (uncontrolled observation of N=1) with chronic fatigue syndrome (nebulous disorder with psychological overlay) that responded to dietary change. Who needs EBM when you’ve got anecdotes?

"Scientific medicine requires ruthless discrimination between what works and what is placebo. Even cherished ideas must be discarded when evidence so demands, as [Surgeon] demonstrated. After building a compelling case for his hypothesis, [Surgeon] revealed that a rigorous trial failed to find bacterial products in portal veins of trauma patients, leading him to abandon his long-held hypothesis for a new one. Naturopaths, on the other hand, cling to outdated ideologies (e.g., acupuncture, homeopathy) despite negative evidence, while paradoxically eschewing proven treatments like vaccination.

"Pre-scientific philosophies and implausible therapies should be studied, to illuminate the psychology of belief. Why not have a lecture teaching us common reasons that placebos fool patients and providers? With such knowledge, we could hope to find diamonds of truth in the rough of alternative medicine. Uncritical promotion of naturopathy, however, is inappropriate at a medical university."

Not quite as good, and it was 6 months old, so I'm happy the homeopath came along in time.

Double Standard

2008-11-21T19:48:00.000-08:00

I've recently gained slight notoriety at my medical school for writing an article critiquing a homeopathy presentation published in the campus newspaper. Here it is, with identifying details changed to protect the gullible:

"On [date], [Homeopath] was sponsored by [alternative medicine group] to teach [school] students about homeopathy. Like a similar [alt med group] lecture a year ago, the presentation failed to address my concern that homeopathy is based on ancient superstitions rather than good evidence. [Homeopath] was charming and sincere, but despite his obvious skill as a pediatrician he seems to have fallen for a double standard.

"[Homeopath] and I agree that the 200-year-old theory behind homeopathy is magical thinking that strains credulity, and we agree that homeopathy should never be used in place of evidence-based medicine We both sympathize with patients frustrated by modern medicine's lack of good drugs for many common complaints. We might see eye-to-eye on the ethically thorny issue of prescribing placebos for self-limiting or untreatable diseases, but that discussion is stymied by a crucial difference: [Homeopath] believes he utilizes the power of homeopathy when his patients reach the limits of EBM, whereas I suspect he is using placebo. He claims that the particular sugar pill he selects for a particular symptom has a specific effect, and this effect, despite being clinically significant, eludes confirmation by controlled evidence.

"I asked [Homeopath] how he responds to physicians who conclude, given the lackluster evidence, that effects of homeopathy are fully explained by placebo. His answer revealed great trust in his personal experience and a bizarre insistence that no one can criticize a drug without using it first. ("You can't knock it until you've tried it" is a CAM favorite, as if experiencing a possible placebo effect makes a human more objective.) I countered that physicians-in-training rely on collective wisdom in the form of evidence-based guidelines; I do not need to personally prescribe thalidomide to a pregnant woman to know its danger. [Homeopath] responded with an anecdote that drove home the point: although he practices most of the time, he justifies homeopathic treatments with appeals to tradition and personal experience.

"Why does [Homeopath] believe in homeopathy? He expresses incredulity that so many people could believe in it for so long if it were not effective, but the "old and popular" practices of bloodletting, racism, and astrology suggest that mass delusion is certainly plausible. He is comforted because FDA regulates the manufacture of homeopathic products, but of course "not contaminated with melamine" is a far cry from "proven safe and efficacious by Phase III clinic trials." He puts great faith in reports of patients whose symptoms improve after taking homeopathic drugs, but the primary rationale for using EBM is that such uncontrolled observations cannot distinguish correlation from causation. His anecdotes are rife with possible confounding effects, such as regression to the mean or concomitant EBM therapy, so how can we know? Randomized controlled trials are the appropriate way to evaluate such complex interventions.

"Homeopaths often deny the power of RCTs to analyze homeopathy because homeopathy's mechanism is mysterious. The history of scientific medicine belies this excuse. Although the value of hygiene, for example, met resistance from physicians who relied on tradition and personal experience, incontrovertible data won the day even before the germ theory of infectious diseases was available to explain them. Similarly, the famous trial showing that lemons cure scurvy saved many lives before ascorbic acid and lysyl hydroxylase were identified.

"[Homeopath]'s claim that RCTs are ineffective because different people respond differently to homeopathy is odd because this is true for many drugs, perhaps through genetic variation in target receptors or liver enzymes. Rather, RCTs are the solution to this problem; carefully controlled studies allow us to identify which groups respond best to which interventions even if we do not understand why (e.g., particular hypertension drugs for African Americans). If his "chronic reactional modes" have validity, then [Homeopath] can assign subjects into appropriate groups and thereby increase the power of a homeopathy study.

"Homeopathy should not be adopted into modern medicine until it meets the same standards of science-based care as other disciplines. [Homeopath] neither showed nor referenced data for the specific efficacy of homeopathy, probably because only low-quality trials show positive effects. Given the implausible tenets of this pre-scientific philosophy, "placebo" is the null hypothesis and the burden of proof is on homeopaths. I celebrate the [alt med group] call for research into old and popular treatments, but such drugs should not be used on patients before good research shows them efficacious."

I wrote it to sound nicer and more charitable than I really feel, partly to avoid excessive nose-tweaking and partly because the speaker (and one of the organizers, whom I've seen in social settings several times) seems genuinely friendly and well-meaning. However, that doesn't excuse intellectual sloppiness in a medical university lecture hall.

Learning the science of medicine

2008-09-22T21:35:00.000-07:00

I have completed the first two years of a typical four-year medical school curriculum. Years 1 and 2 are often referred to as "the basic science years" to distinguish their content and style from "the clinical years" 3 and 4. Here I will describe the contents of Years 1 and 2 at my school, but national licensing requirements mean that most US medical school will be similar.

Year 1 starts with gross anatomy (involving cadaver dissection), embryology, biochemistry, and genetics, followed by histology, physiology, and neuroscience. I describe Year 1 of medical school as "how the body works." From molecule to cell to tissue to organ to system to organism, students learn the structure and function of the human body. Many of the lecturers are PhD scientists who actively research a particular course topic, and these faculty slip in tidbits from the edge of knowledge in their field. Most of the material, however, is a collection of facts and models firmly established by prior work, sometimes decades ago. Students learn from ponderous textbooks edited by legends and streamlined review books targeted at the national licensing exam. Any starry-eyed love of knowledge is generally overwhelmed by a desperate need to learn the facts for the test.

Year 2 begins with immunology and microbiology, the scourges of humanity since antiquity and the body's defenses against them. The technologies of molecular genetics have caused explosions of understanding in these fields over the past few decades. Material here is noticeably fresher and the textbooks hotter off the press. Since I entered medical school, a new class of helper T cell has been discovered and described, and it will likely be added to the curriculum before I leave. However, like in the first year courses, the syllabus reflects consensus views in the field; medical students have neither time nor reason to learn the controversies in the fine print. Year 2 reaches its crescendo with pharmacology and pathology, which obviously must be updated frequently as new drugs are discovered and diseases are better understood, and also includes nutrition and epidemiology. I describe Year 2 of medical school as "how the body goes wrong and how we can fix or prevent it." Emphasis is still largely on didactic formats; much more time is spent with books and flashcards than with stethoscope. Knowledge transfer is largely one-way, as one can not easily talk back when trying to drink from a fire hose.

Year 2 culminates with the United States Medical Licensing Examination (USMLE) Step 1, a multiple-choice test that takes 8 hours to write and upwards of 2 months to prepare for. It is widely described as the most difficult exam of a physician's career. Anything from the first two years of medical school (which involves learning more facts than most four-year undergraduate programs) is fair game.

I cannot speak from personal experience about Years 3 and 4, but I have seen friends travel through them. This time is spent largely in the clinic, following physicians and participating in patient care. Students learn practical skills like how to navigate the hospital, how to interact with patients and staff, and how to keep good records. When they're lucky, students will be taught a procedure or allowed to make a suture. My impression is that learning comes not only from textbooks but also from the medical literature, such as from reviews outlining current evidence-based guidelines. As students advance, they face greater expectations to be able to cite major studies and statistics that justify particular treatments. Fourth-year students and residents often participate in clinical research, learning how evidence is generated in order to improve the practice of medicine.

Medical education necessarily begins with rote memorization and much learning of dogma. In a sense, Years 1 and 2 teach students the language of medicine, the foundation upon which useful knowledge and skills will be built. In no way is a medical student competent to practice medicine after passing USMLE Step 1! That milestone is merely a sign that the student is ready to truly begin a training process that will last five to ten years, past graduation and through residency in a slow transition from apprentice to autonomous physician.

I have learned an important distinction about "the basic science years" since leaving medical school for graduate school. The curriculum of Years 1 and 2 of medical school do not teach science so much as the fruits of science. Science is a process of hypothesis- and evidence-driven inquiry. Years 1 and 2 focus not on this process but instead on the facts and models that science has established. Medical students do not learn how to be a biochemist; rather they learn what the biochemists have discovered. Years 3 and 4, I presume, are when students begin their training in the practice of clinical science, and I imagine that most progress on this front happens during residency and beyond.

This distinction is important to consider when evaluating claims such as: "naturopathy students are trained in the same sciences as medical students." Learning anatomy and biochemistry is a necessary step in becoming a science-based physician, to be sure, but it is far from sufficient. Medical graduate education is unparalleled in its transformative power, and I look forward to experiencing it.

Life is Awesome

2008-08-31T17:29:00.000-07:00

The complexity of life fills me with awe. Contemplation of huge numbers often makes me gasp and shiver: a New York City subway train speeding by with car after car after car jammed full of persons, each with joys and concerns equal to my own, all together whom make up a functioning city; the Grand Canyon, so deep and long and old as to mock human ambition; the “pale blue dot” photograph of Earth adrift in a colossal solar system, itself meaningless in size within our universe. I love the “order of magnitude” display outside the Hayden Planetarium at Museum of Natural History. But I didn’t pursue economics or cosmology, fascinating as they are, because they don’t hold a candle IMHO to the wonder of living organisms. Trying to comprehend the elaborate dance of molecules, cells, tissues, organs, and systems that make up a single human body throws me into a reverie that might be described as religious. The Quakers are on to something when they proclaim to see “that of god in everyone.”

I am reading an immunology text book to brush up on my basic understanding of the subject in preparation for a meeting with my thesis committee. Only on the second chapter I have already had to stop several times to marvel at the interconnectedness of the dance of immune cells and molecules. As I type, stem cells inside my femurs are constantly making more red blood cells than I can use, just in case I suddenly cut myself and lose blood; unless and until trauma happens, the excess cells commit suicide and are cannibalized. In my lung, epithelial cells continuously make and secrete molecular signals telling resident macrophages not to cause inflammation; in the event of infection, the macrophage is un-muzzled in order to quickly attack an invading pathogen. My lymph nodes have an architecture of discrete regions maintained by chemokines, secreted proteins that allow white blood cells to home in on their target like a shark sniffing blood; when a white blood cell is activated, it expresses different chemokine receptors that guide it towards different locations in the node and then to the infected tissue. So-called “natural killer cells” slink through my body on endless patrol, checking the identification badge of every cell and violently reacting to any that looks foreign or infected. What tremendous expenditure of energy, what staggeringly dense network, what a piece of work is man!

Some admirers of life decide that only a non-human designer can explain the complexity of life. Sharp thinkers, of course, will realize that this conclusion begs the question: what then explains the complexity of the designer? Recognizing that our limited brains reflect the demands that shaped them—our chimp-like ancestors had no need to understand a trillion-partner dance or the billions of years that shaped it—let us admit that reality may simply be too complicated for us to comprehend without approximation and analogy. The acknowledgment of no external engineer does not diminish but rather enhances the majesty of the dance! Reflect on the absurd connections between tiny DNA molecules, the proteins they encode and cells they instruct, and our conscious experience of living; I challenge you not to shudder in amazement. Reverent appreciation of evolution and emergence is surely the future of religion.

From in vitro to in vivo and beyond

2008-08-10T11:40:00.000-07:00

I'm currently listening to the audiobook version of The Great Influenza, which describes the context and events of the 1918 pandemic flu. This virus killed more humans in a year than any other pathogen throughout recorded history. More people died from this flu than died from trauma in the contemporaneous world war. It is a shocking piece of history.

I've only listened to half the book so far, so I'm still watching the stage be set. I've been very interested to hear about the birth and growth of modern medicine in America. Two centuries ago, medicine in this country was still pre-scientific, meaning treatments were based on ancient authorities rather than on evidence from controlled experiments. Blood-letting was popular treatment for a variety of ailments, for example, and disease was described as imbalance among the four humors. Just as many sectarian religions were spawned in this "Wild West" period of American history (e.g., Mormonism), sectarian philosophies of health (SPHs, my term) sprouted and spread like wildfire. Given that physicians were largely incompetant at diagnosing or treating disease, it is small wonder that SPHs like homeopathy would arise; pure placebo is a great alternative when going to the hospital increases your chance of death. More on SPHs in posts to come, because sadly many still exist to this day despite being firmly based on magical thinking from a pre-scientific time.

Once scientists began studying human physiology and pathology, of course, medicine became not only safe but incredibly effective. Major early strides were in combatting infectious diseases from viruses and bacteria. Three specific tools were: vaccines, pieces of dead or weakened pathogens given in advance of disease to generate long-lasting, protective memory; antitoxin, serum from immunized animals given intravenously to acutely ill humans so that the animal's antibodies could neutralize toxins or pathogens; and antibiotics, chemicals purified from fungi or bacteria that killed or slowed the growth of an invading pathogen. (Non-specific but equally important techniques included a commitment to cleanliness in the hospital and sterility during surgery.) The discovery, testing, and manufacture of these biochemical tools depended on experimentation in animals, a strategy that only can seem reasonable after widespread acceptance of evolutionary biology.

How do researchers choose and justify the use of a particular species? Phylogeny is crucial when comparing findings in animals to humans, so immunology studies in mammals are by far the rule, but practical concerns also matter. For example, insulin for diabetics can be harvested from pigs and antitoxin drained from immunized horses, because these mammals are large and easy to manage. The ubiquity of mouse and rat in biological research is due partly to phylogeny (their physiology is surprisingly similar to humans') and partly to convenience (breeding and storage is inexpensive). As long as an animal model of disease is sufficiently similar to the human disease of interest (e.g., do these mice become diabetic in the same way as humans?), animals studies are a great way to sidestep the problems of expense and ethics with human studies.

Why not just study cells in a dish? Biologists now routinely isolate and grow human cells, and such experiments are called in vitro (in the glass) as distinguished from in vivo (in the living) animal experiments. The problem with in vitro is the ultimate problem with the technique of redunctionism in general: the whole is often more than the sum of its parts. It is very important to understand the function of each type of immune cell, but that knowlege is incomplete without understanding of how those cells interact. Like the nervous system, the immune system is a network of hopelessly interconnected players, each regulating the other. My advisor is fond of saying, "You can put eosinophils in a dish and make them kill any kind of worm," but many worms are expelled as usual from animals lacking eosinophils. Immunology research is moving more and more away from in vitro work and towards in vivo studies, because the former are not always helpful in understanding a complex system.

As an analogy: you're more likely to avoid malnourishment by eating a variety of food types than by taking a Centrum and eating only Twinkies. We may not have yet isolated all the essential micronutrients to put in the Centrum, the method of ingestion might be important for absorption (i.e., as a fruit works but as a pill doesn't), and the combination or timing of nutrients might be off in the pill diet (e.g.).

Because mice in particular have been used for so long, many carefully bred strains are available. Several different inbred strains of mice have been maintained for decades. Each female BALB/c mouse I use in an experiment is genetically identical to every other female BALB/c ever used in experiments all over the world. More recently, genetically modified organisms have become available that either lack or over-express one particular gene. For example, I have mice that look like BALB/c in every way except that they lack a functional gene for iNOS, an important enzyme in immune responses (the mice are called "iNOS knockouts"). It gets even more specific: I have mice that lack the gene Arginase only in their macrophages (using the Lox-Cre system). On the flip side, we also have mice that over-express a gene, or express a gene not normally found in mice (like green fluorescent protein from jellyfish).

The amazing extent of engineering that has gone into mice has resulted in animal that are more akin to manufactured lab materials than individual organisms. This transformation makes for terrific control and predictability, but at what cost? It is far easier to cure disease in genetically identical mice raised in identical environments than it is to find a drug that works in humans. By breeding out so much variability in our animal models, we risk getting results that are too specific to the particular clone under study. Perhaps a promising new vaccine, for example, works because of a particular feature of BALB/c mice, and it will not work so well in a mixed mouse population.

The August 1 issue of Science includes a report about nine children with a genetic deficiency in a molecule named MyD88. This signaling molecule has been studied extensively in mice, and its function has been dissected using knockout strains. Mice lacking MyD88 get terribly ill from a variety of infections; these humans lacking the same gene, however, were mostly healthy with increased susceptibility to only a few types of bacteria. Whoops. What does this mean for all the molecular biologists who have defined careers by study of this molecule in mice?

Animal models using inbred strains have been a remarkably powerful tool in understanding the biology of health and disease. As we study more complex systems and subtler effects, however, I predict that we will need to loosen our grip on individual variability within our test subjects. As in vivo animal experiments get closer to in vitro levels of control, they get more removed from the messy reality of human diversity. I imagine pharmaceutical firms test new drugs in many strains of animals before proceeding to human trials; perhaps basic scientists should do the same at some point to confirm that findings are relevant. This balancing act is typical for scientific investigation: more simplified means easier to reach conclusions, but too simplified means conclusions that don't adequately reflect reality.

Finally, it is worth reflecting on the ethics of manipulating organisms in this way. I welcome reasonable discussion, but hopefully we all agree that violent terrorism is unacceptable.

Monopoly or Standards?

2008-08-04T17:09:00.000-07:00

A student sent the following email to our entire school:

Take action now for your freedom to speak about nutrition.

Your role is simple: Dial the numbers below and say, "I'm calling to oppose Senate Bill 1941." This bill proposes that in New Jersey only Registered Dieticians will be allowed to speak with clients about nutrition.

Joseph Vitale: (732) 855-7441
Robert Singer: (732) 901-0702

The ADA has worked state-by-state to pass turf legislation that excludes everyone except registered dietitians from giving nutritional advice.
They've now moved into New Jersey.

The ADA's mission is to serve the public as "the most valued source" of good advice about food and nutrition. But did you know that this "valued" nutrition resource receives substantial funding from food corporations?

The ADA receives more than $3 million from Wendy's, McDonald's, PepsiCo, Taco Bell, Hershey's and more. On the ADA website you'll find tips on how to make a family dinner healthier-sponsored by Wendy's!

Read more about troublesome partnerships with the food industry:
http://www.inthesetimes.com/article/3447/corporate_potluck/

"American Diabetes Association peddling nutritional nonsense."
http://www.naturalnews.com/008164.html

The experts speak out against Bill 1941:

Dr. Neal Barnard, founder and president of Physicians Committee for Responsible Medicine says: "If standardization of the nutrition practice is left in the hands of a single professional organization, the potential bias caused by financial arrangements raises important questions.It is a dangerous mistake to establish in law a monopoly on nutritional counseling."

Dr. Michael Jacobson, executive director of the Center for Science in the Public Interest says: "I'm very troubled by laws that prevent anyone-including professors of nutrition-from giving nutrition advice, unless they are registered dietitians."

If this bill passes, millions will be impacted. The bill claims that the health and welfare of the residents of New Jersey will be protected by identifying to the public those individuals who are qualified and legally authorized to practice dietetics/nutrition. The citizens of New Jersey certainly need protection-but not from Health Counselors.

The time to call is now! Pick up the phone to have your voice heard.

Your urgent call to action is simple:
1. Make the call now.
2. Forward this email to everyone you know.
3. Ask them to call and forward this email.

Although I don't know much about American Dietetics Association (ADA), I have several concerns about this email. Most importantly, no link is given to the text of the bill. Are we, as future professionals, expected to call politicians without actually reading the primary source? Here it is.

The point of state licensure seems threefold. First, it is a nice way for the state to collect fees from professionals. Given the state of the budget, I don't object to this redistribution. Second, it is a way for a professional societies to control the number of practitioners. This is not necessarily good for the public, especially in ridiculous cases like licensure for interior decorators. My emailer emphasizes this point with talk of monopoly. Third, it helps guide the public towards sources more likely to be science-based and enables easier prosecution of quackery and fraud. For medicine and surgery, the befits of this third point clearly outweigh the downsides of the second point. It would be an interesting debate as to whether the same can be said for nutrition.

The email cites a partnership between ADA and Wendy’s as evidence, presumably, of registered dietitians (RDs) being too conflicted to give scientific medical advice. Please check out this project before demonizing it. It seems mostly benign and useful to me, and in fact it is possible to have a healthy meal at Wendy’s. If Wendy's helps parents concerned with nutrition find their best menu items, then that value perhaps outweighs any societal harm from the restaurant getting good publicity.

More broadly, this argument is akin to saying, "anyone should be allowed to practice medicine because the AMA collaborates with pharmaceutical companies." Corporate influence in medical societies is indeed an important topic of concern, but the unfortunate fact of Pharma-sponsored CME courses does not mean that physicians are no better than homeopaths. Physicians, with their dedication to patient well being and science-based practice, are still the best option despite some conflicts, and the same might be argued of registered dietitians.

The email gives two links to news stories suggesting corporate influence on ADA, but one story actually discusses the American Diabetes Association (not Dietetic). I know that the two associations collaborate on a cookbook, but aside from that I can find no formal connection. This is probably an honest mistake, but the email's argument is much weakened if 50% of its links are irrelevant.

Quotes were given by the leaders of two organizations, Physicians Committee for Responsible Medicine (PCRM) and Center for Science in the Public Interest (CSPI), decrying the ADA’s initiative.

PCRM apparently is made up mostly of non-physicians and has strong ties with PETA. AMA has issued resolutions condemning PCRM for disguising animal liberation ideology as medical advice, and ADA has refuted PCRM claims that meat and dairy products are unnecessary in the diets of most people (references here). I do not consider PCRM founder Neal Barnard to be an unbiased expert when evaluating ADA-sponsored legislation that seeks to regulate nutritional counseling.

The only criticisms I found of CSPI were that its tactics as a public health advocate are quite aggressive. It seems to represent Nader-like politics, making it reviled by libertarians and corporate interests. I find this quote a bit more valuable than the first, but again neither the man quoted nor anyone on the CSPI board is a physician. If you were to pick two "expert" quotes to convince medical students, are these the best to choose?

I am not throwing my support behind this bill, but I have not yet been convinced that it will be bad for anyone but certificate holders in integrative nutrition (unless they also have an RD, an MD, an OD, a BSN, or any other licensed degree in healthcare). Any sadness for that crowd's loss does not outweigh my concern that the public be given guidence to navigate the bewildering maze of conflicting claims about health and nutrition. With all the fads and superstitions in the marketplace, it is an appropriate role of government to support the practitioners who strive to be science-based.

Hygiene Hypothesis

2008-07-26T07:35:00.000-07:00

In 1989, epidemiologist David Strachan reported that prevalence of hay fever and eczema correlated inversely with family size and birth order. He suggested a causal mechanism: more siblings means more unhygienic contacts, which means more childhood infections, which might be protective against allergic diseases. Strachan had no evidence yet for the mechanism, but his speculation gave birth to the "hygiene hypothesis."

The hygiene hyopthesis, that early exposure to microbes is protective against allergic disease, is immediately intriguing to those of us who love claims that something "bad" is really "good for us." As scientists are wont to do, many researchers have tried to replicate and expand Strachan's findings. Unfortunately, the evidence has been decidely mixed. Check out this comprehensive and very readable review, a summary and update of a report commisioned by International Scientific Forum on Home Hygiene and the primary reference for this essay.

First of all, the increase in allergic asthma seems real and quite dramatic between 1970 and 2000. Environmental factors are strongly suspected; consider that the lower asthma rate in East Germany quickly rose to match that of the genetically similar population of West Germany after the wall fell. Importantly, any alleged lifestyle or exposure change must temporally match the period of disease increase. For example, the decline in severe infections (polio, small pox) thanks to vaccination preceded the asthma rise by decades, as did the use of household cleaners containing bleach, so those changes probably cannot be invoked by the hygiene hypothesis. Although modern facilities and greater awareness of microbes suggests that homes must be more hygienic now compared to fifty years ago, studies of kitchens and bathrooms (and even hospitals, sadly) reveal that we are not as good at sterilizing as we think.

Connections between allergic disease and family structure have generally been supported, as has the protective effect of early exposure to farm animals (though not lifelong or occupational exposure) on allergic asthma. To leap from correlation to causation, however, we need to find the biological mechanism underneath these relationships. Changes in no particular viral or bacterial disease match the rise in allergies, except for diseases that themselves correlate with hygiene and socioeconomic status (hepatitis A, tuberculosis). Childhood antibiotic use seems to correlate with allergies risk, but perhaps the same factors lead to susceptibility to both allergies and respiratory infections. Some investigators suspect a more subtle change, such as in the composition of the gut flora, potentially affected by diet and environmental factors, which has an important role in training the host immune system how to discriminate between the harmful and the harmless. Zooming in further, can the actions of immune cells explain why fewer infections might lead to allergies?

Early models of how decreased pathogen load might lead to an increased risk for allergic diseases focused on the Th1-Th2 dichotomy. T-helper (Th) cells are like the coaches of the immune system team; they release chemicals (cytokines) that instruct other immune cells on how and where to fight a particular invasion. Many intracellular pathogens (viruses and some bacteria) trigger a "type 1" or Th1 response, characterized by the cytokine interferon-gamma and activation of immune cells that engulf or destroy infected host cells (neutrophils, macrophages, natural killer cells, cytotoxic T cells). A "type 2" response is instead induced by multicellular parasites (helminths such as hookworms, tapeworms, and flukes), and Th2 cells use the cytokine interleukin-4 to mobilize immune cells that can secrete antibodies or chemicals to damage the invader (eosinophils, basophils, mast cells, B cells). A burgeoning Th1 response will inhibit the formation of a Th2 response, and vice versa, and for some time immunologists believed that the two programs were mutually exclusive. The final piece of the puzzle seemed to be that Th2 responses are associated with allergic reactions. The story became: fewer microbial challenges during childhood means less Th1 activation, which means net polarization towards Th2, which leads to susceptibility to allergies.

This Th1-Th2 polarization story was very tidy and satisfying, but it had some glaring flaws. First of all, along with allergic asthma have been rises in autoimmune and inflammatory diseases, such as Crohn's and multiple sclerosis, that are not mediated by Th2 pathology. Can they fit into the hygiene hypothesis? Even more troubling was data showing that helminth infection decreases susceptibility to and severity of allergic diseases!

A more recently described subset of T cells are regulatory T cells (Treg cells) . The hallmark cytokine of Treg cells is interleukin-10, which acts generally as a suppressive signal. Whereas Th1 and Th2 cells activate and expand immune cells in order to combat a pathogen, Treg cells reign in the response when the fight is over or simply not worth fighting. Just as any effective medicine or surgery has undesireable side effects, the weapons of the immune system damage host tissue along with pathogens and infected cells. Ridding the body of, say, streptococcus is worth some collateral damage, but Treg cells are necessary to stop an overzealous immune system from doing more harm than good. A common thread through allergic, autoimmune, and inflammatory diseases is inappropriate activation of immune cells, and many different versions of these diseases are ameliorated by Treg cells.

Helminths trigger Treg cells. Although the host developed the Th2 response to kill the parasite, the parasite developed molecular tricks to induce the more peaceful Treg response, and this evolutionary arms race settled into an uneasy truce of a subdued Th2/Treg mix. Hence, most helminth infections have relatively low morbidity (assuming the host is well nurished), which suits both host and parasite.

What happens when years of arms race ends with one opponent abruptly collapsing? Thanks mostly to sanitation (many helminths spread by the fecal-oral route) and also to highly effective drugs (intestinal helminths, if paralyzed, are quickly expelled by gut peristalsis), most people in industrialized countries are never infected by helminths. Although at first this change sounds like an unqualified good, such a disruption of a complex ecology (make no mistake, your gut is an ecology of symbiotic microbes) is bound to have some negative consequences.

These days the hygiene hypothesis is often formulated as follows: less exposure to helminths leads to lower levels of Treg cells, which leads to less suppression of immune responses, which increases susceptibility to allergic (Th2), autoimmune (Th1), and inflammatory (Th17, another new subset) pathologies. Intriguing trials by Joel Weinstock show amelioration of symptoms in Crohn's patients infected with pig whipworms. In the lab, immunologists and parasitologists are trying to find the molecular means by which helminths induce Tregs; a purified protein would likely have fewer risks than infection with live parasites. For patients with severe, poorly controlled disease like Crohn's, however, the risk of infection may be outweighed by its benefits.

Part of the power of science and medicine is in reductionism. The risk of this method is oversimplification of a complex network; in this case, elimination of parasites may have had both good and bad effects on our health. What makes one organism "parasitic" and another "symbiotic" if even the parasites play a role in healthy homeostasis? Is there a "Goldilocks" level of parasite burden, a balance between infectious disease and unhealthy sterility? Given my family history of Crohn's, I asked Joel Weinstock, half-jokingly, if I should infect myself prophylatically. He responded, half-jokingly, "Maybe you should."

Student, Heal Thyself

2008-07-19T20:35:00.000-07:00

It’s funny how I didn’t notice much anxiety about my corrective eye surgery (preformed 7/10/08), or even much excitement until it was actually scheduled. I had one friend who expressed a lot more excitement than I did before the surgery was imminent, and another who was very nervous for me; interestingly, each of them has 20/20 vision. The enthusiastic friend helped goad me forward (probably over my unacknowledged anxiety) until my own anticipation took over, and the worried friend asked questions that helped me focus on exactly why this surgery was important for me.

Most people cannot appreciate, I think, what it means to have a -9 diopter refraction error. I was too nearsighted to read a book. If glasses could not correct my vision, I would be legally blind. Luckily, I was nearly 20/20 with glasses or contacts, and I had worn contacts daily with no major incident for 13 years. My anxious friend, worried about the risks of surgery, made the analogy, “It’s like a temporary tattoo or the real deal.” The flaw with this analogy is that I was looking at 60+ years of applying the temporary tattoo every day, versus getting inked once. True, there are risks from (any) surgery, but there are also risks to “business as usual.” Daily use of contact lens is not without risk. This risk may be small in the short-term, but over a lifetime its “expected value” is probably worse than that of a one-time surgery that eliminates need for contacts. A good lesson can be generalized: “doing nothing” in the face of a medical condition is not the “safe” default, but rather just another option with its own benefits and risks.

Furthermore, imagine if I’m at hour 20 of a 36-hour call shift when my contact lens tears or my glasses break… now I am non-functional and patients could suffer. As said by my parents (who generously paid for the expensive procedure), this is not really elective surgery for someone in my circumstances.

The pre-operative evaluation was two hours of staring into a dozen different high-tech instruments as my eyes were measured in every way. Some measurements were repeated by another technician, just to be sure! The rigor was comforting. Of course it involved atropine drops, which left me dilated and unable to read until the next day.

All procedures that correct vision with lasers involve reshaping the cornea. Review the anatomy. A myopic eye fails because it is “too long” for its lens; the lens improperly focuses incoming light to a point in front of the retina (instead of on it). After some of the cornea is shaved off with an excimer laser, the incoming light hits the lens at a different angle such that the image now focuses on the retina. The two major corrective procedures are LASIK (laser-assisted in-situ keratomileusis) and PRK (photorefractive keratectomy): LASIK involves cutting a flap and applying the laser to the cornea under the flap, whereas PRK involves applying the laser to the surface of the cornea. LASIK is great for short-term comfort; only the seam of the flap needs to heal, and most patients are 20/20 the day after surgery. PRK is worse in the short term, because the tiny epithelial layer (a couple cells thick covering the cornea) is destroyed and must be re-grown. The advantage of PRK is more corneal thickness to work with, because the LASIK flap uses up 100 micrometers of cornea (average cornea is 550 micrometers thick and mine was 535). Since high correction means more cornea shaved away, surgeons prefer PRK for a patient like me. See a good description and illustrations here.

See the 10-year follow-up data on PRK for severe myopics. At 10 years, 78% of patients were within 2 diopters of perfect vision. I will consider my operation a success even if I still need glasses, so long as I am not dangerously helpless without them.

On the day of the operation, Mom drove me to the surgeon’s office. After reviewing and signing a consent form, I was given a Xanax and left to relax for 30 minutes. After I was happy, I entered the operating room and lay down on the table, which was cushioned and had a hole for my head, so that at rest my head tilted back comfortably. The surgeon sat at the head of the table and spoke to me through the entire procedure. My face around my eyes was sterilized, and my left eye was covered. My right eye was taped open and an anesthetic drop ensured that I felt no discomfort. Above me suspended the business end of the laser. As I had no glasses and the room was dark, all I could see was a flashing green light at the center circled by four red lights; the doctor told me to focus on the green. First came an ethanol solution dropped onto my eye, resulting in immediate and dramatic blurriness (beyond my usual uncorrected blurriness, which is impressive). Ethanol denatures proteins, and in this case I imagine it disrupted the tight junctions between my epithelial cells and the collagenous Bowmen’s membrane underneath them. The doc used a tool to remove the loosened cell layer, giving me the visual effect of sitting behind a splattered windshield as someone scrapes it clean. Again I stared at the flashing green dot.

Now the doc positioned my head and held it gently in place with his hands. The laser began operating, with three effects. First, I heard it hum. Second, I smelled its ozone exhaust, which gave the impression of burning tissue. Third, as I stared at the green light, my blurry vision slowly came into focus! Perhaps without Xanax this experience would be unsettling, but I was biting my tongue because I didn’t want to move my head by exclaiming, “This is awesome!” Luckily the laser (whose operation is automatic) tracks the pupil and can adjust for small movements by the excited patient.

Next came an anti-inflammatory eye drop to prevent scarring, followed by flushing with ice-cold water. This last step was a bit unnerving; imagine “brain freeze” in the back of your eye. But then the eye was done; right eye was patched and the left was uncovered for its turn. All in all, I was in the operating room maybe 20 minutes.

The following three days were painful. My eyes felt dry and irritated, I was exquisitely light-sensitive, and my vision was only marginally better than it had been before. This blurriness couldn’t be fixed with glasses, though, because it was due to my lack of epithelial cells, a very different problem from standard myopia. A week later I could read, use the computer (with some difficulty), and probably drive, though I’m still using public transport just to be safe. I expect more big gains over the next week as my new epithelium organizes itself, but I’m told that haziness and halos slowly fade over 1-3 months. Already it’s amazing how well I can see without correction!

I have been blessed with excellent health, with the exception of my myopia. I think it is good for me, as a future physician, to have undergone this procedure. I need to practice what I will someday preach, trusting my health in the hands of a physician when the risk-benefit ratio so demands. I now better appreciate the stress and effort of a patient before and after a surgery, as well as the demands on his family. Of course, I didn’t risk my precious eyes with just any surgeon; I asked friends in ophthalmology and found the best doc in the area. He was probably more expensive than less skilled surgeons, but what is the point of money if not for securing health and happiness?

Walk the Line

2008-07-14T14:57:00.000-07:00

How best do physicians intervene to maximize patient health and minimize the burden of disease? In the face of sophisticated understanding as well as vast ignorance, the professional healer asks, "What is most likely?" Despite never being certain, the physician must act with confidence, informing her decision with the tools of science and stastics. There is a balance to be struck here, between appropriate humility in the face of a chaotic world and the arrogance needed to save a life.

This blog is named in honor of William Gosset, a statistician employed by Guinness, whose t-test helps us answer that question, "What is most likely?" We humans are notoriously bad at discerning causation from chance correlation, and our tendency to falsely detect cause leads to all manner of superstitions. Stastical tests like Student's t help us quantify how likely an observed difference would be due to chance. All scientists must master this thoroughly nonintuitive process; they must shed their human biases in order to think like machines, rigorously controlling and replicating every step of an experiment. The practitioner of medicine bears an extra burden, for he must operate under this stern logic of stastics while maintaining the empathy needed to communicate effectively with (human) patients.

While many scientific disciplines have pre-scientific origins, modern medicine may be unique in having prcursors in nearly every culture in history. Societies across the globe have had unique theories of health and disease, since long before microscopes and double-blind trials. The folklore of pre-scientific healers has a proud legacy in modern medicine, leading to many early drug discoveries, for example (see aspirin, digoxin, morphine). Not all superstitions hint at great truth, however, so yet another line must be walked by the physician-scientist: with how much effort should she study pre-scientific remedies that have not yet yielded fruit in the meritocracy of scientific medicine? Surely there is a risk of overlooking a diamond in the rough, but just as surely every research dollar is precious.

Through this blog, I hope to explore these balancing acts and more as I begin my career in medicine. I look forward to feedback and discussion!