We Don't Know
Dr. Newman, phone call, 6800."
"Emergency department, Dr. Newman," I answered, thinking the call was likely to be a doctor's office sending me another patient on a busy Monday.
"T, honey?" She used my childhood nickname, as she always does.
"Yes, sweetie." She forced the breath between her lips. "Honey, something's wrong. I need some help."
"What do you mean, Mom?" A knot started in my stomach. My mother is stoic and selfless, and doesn't ask for help (she doesn't want to impose). That she was asking for help and "bothering" me at work were both ominous signs.
"It hurts in my stomach, baby. It started a few minutes ago, all of a sudden. I don't know what to do."
"Are you at work, Mom?"
"I'm calling an ambulance for you. You're going to come here now."
"No, sweetie, thank you, but that's too much drama for the office."
I shook my head. She apparently believed that she could settle gently to the floor like a leaf, passing quietly into the next world, and that this would be preferable to causing a scene.
"Give Heather the phone, Mother."
I spoke to her assistant at the next desk, who was, as I would've guessed, oblivious not because of inattentiveness but because my mother doesn't complain. Heather escorted her into a cab and brought her to the emergency department. When she arrived, she was doubled over and visibly short of breath. A colleague I trust and respect evaluated her.
My colleague performed a rapid history and physical examination. She had blood drawn for tests, chest and abdominal X-rays, an electrocardiogram, oxygen administered through her nose, a heart monitor, and two intravenous lines placed in her arms all within the first few minutes. Tests for liver disease, pancreatitis, gallstones, internal bleeding, ulcers, gastritis, and kidney stones were normal. Blood tests and X-rays for her heart and lungs were normal, and she showed no signs of serious infection. She underwent a computed tomography (CAT) scan of her abdomen to evaluate her intestines, her appendix, her aorta, and the rest of her abdominal organs, and we did a bedside ultrasound to see her liver and the blood vessels in her abdomen. All of these were normal. And slowly she began to feel better, with no particular treatment.
After three hours of observation and a battery of test results, the colleague I had handpicked to see my mother shrugged sheepishly, apologized, and said, "I don't know, I just don't know. I'm just gonna call it 'abdominal pain.'"
"Undifferentiated abdominal pain" was my mother's diagnosis. It is a trash-bucket term that means we don't know what caused the problem. It also means we have found no reason to believe it's dangerous (arguably good news), and it's likely, though not guaranteed, to go away without any particular treatment. In other words, we don't know what caused it, we don't know what to do about it, we don't know if it'll come back, and we don't know where to go from here. Undifferentiated abdominal pain could more accurately be called a nondiagnosis.
What's perhaps most remarkable about my mother's experience is how utterly unremarkable it is. Mom got better. As inexplicably as her pain appeared, so too did it disappear. Over the next few days she went for an official ultrasound of her liver and gallbladder, and two follow-up appointments with her physician. The nondiagnosis did not change. Roughly 40 percent of visits to the emergency department for abdominal pain are ultimately categorized as undifferentiated abdominal pain; no definitive diagnosis is made and no successful diagnostic or therapeutic procedure is performed. What's surprising, however, is how rarely doctors say the words "undifferentiated abdominal pain" to the patients who experience the problem. Much more often a provisional, specific diagnosis is given maybe "peptic ulcer disease," or "ovarian cyst," or "colitis," but when a physician makes one of these diagnoses, it's often based on what we call "clinical criteria." In other words, we take an educated guess, but we don't know.
An extremely common example of a provisional diagnosis is "gastritis," or inflammation of the lining of the stomach. Gastritis is usually associated with nausea, vomiting, and pain, and can be precisely and accurately diagnosed only by looking at the inside of the stomach through a camera. This requires an invasive test called "endoscopy," and we rarely do it in the emergency department (except in extreme, life-threatening situations). Therefore, while gastritis is a common provisional diagnosis in emergency departments and medical offices, the only method to definitively diagnose it is rarely performed in emergency departments or medical offices. And disturbingly, studies have shown that when physicians think the problem is gastritis, they are frequently wrong.
Abdominal pain is only one example from a long list of symptoms or conditions that, despite its advances, modern medical science cannot diagnose or explain. Do you know what causes the sound of knuckles cracking? No? Nor do I. Ask an orthopedist or a dedicated hand surgeon or a rheumatologist and you may get three different answers. In order to determine the mechanism of knuckle-cracking sounds, the House of Medicine has launched meticulous studies, including one that uses minimicrophones to document and gauge the amplitude and decibel level of the sounds produced. But we have no definitive answer. Do you know what causes memory loss or unconsciousness when a concussion occurs? Neither do we. Do you know what a concussion actually is, at a biological or cellular level? Me either. Do you know what epilepsy is, or what causes the seizures that characterize this condition? Ditto. The list goes on and on. While we can cure some previously fatal cancers, rid the world of scourges like smallpox and polio, and map the human genome, we don't know what makes a knuckle crack.
Comprehending the cracking of a knuckle may seem relatively unimportant, but as a symbol of the vast and uncharted range of biomedical science, it's not trivial at all. Grasping the limits of physician knowledge is critical to deriving a benefit from medical care. Unfortunately, physicians often act as though they know all the answers, and patients often presume that physicians know them, when in fact physicians do not. This combination of unconscious prevarication and mutual misunderstanding is one of the wedges that has forced open the chasm between doctors and patients. As a result of this dysfunctional paradigm, when a diagnosis, or even a cause for a diagnosis, is unknown an entirely common and reasonable occurrence, given the state of our science people become angry. And in America, anger is often followed by lawsuits.
An example of this, one that is not unique but that garnered an unusual level of popular media coverage, is the story of silicone breast implants and the legal actions and FDA proceedings that followed. Contrary to the number of successful lawsuits that have convinced juries of a link between silicone breast implants and lupus (and other, similar diseases), the research on this supposed link is fairly conclusive: the incidence of lupus among women who've had silicone breast implants is the same as the incidence of lupus among women who haven't had breast implants. Any woman can develop lupus, including those with silicone breast implants, but the two are not related.
Difficult as it may be to understand for frustrated women who develop lupus shortly after getting implants, it is a fact. Lupus is a poorly understood disease of the human immune system that can cause rashes, joint pains, kidney disease, and other serious problems, and while it's not very common, it occurs frequently in women in their twenties and thirties, the same age at which many women obtain breast implants. By random chance alone, then, there was bound to be crossover between these two populations but no association has been established. Unfortunately, however, while we seem to have ruled out silicone breast implants as a cause, we don't know what does cause lupus or rheumatoid arthritis, or scleroderma, or the other autoimmune diseases that misguided lawsuits have claimed were related to silicone implants. If we did know the cause, then the frustration of coping with these diseases would be channeled into a cure, and any effort to hold silicone responsible for lupus would be less likely to find support in a courtroom or anywhere else.
The bottom line with lupus, with knuckle cracking, and with much abdominal pain is that we don't know what causes them, and we don't know what to do about it. Given the blistering pace of biomedical advances and technology, one would think that our biomedical knowledge would grow every day, and in some ways it does. But this immense "we don't know" category also grows every day.
Erica shrugged. "I know, I can't believe it either." The physician ID tag clipped to her belt with a photo of Erica's enthusiastic smile seemed out of place, a glib reminder of how quickly life can turn.
Ian shook his head in disbelief while Mark, Cary, and I stared at Erica, confused. "Multiple sclerosis? You're kidding. Wow. Blurriness? That was it? Wow." Ian had never been accused of eloquence, but he was voicing what all four of us were thinking. As residency classmates the four of us had grown close, and Erica was one of the brightest, best doctors I've ever known. She had just been diagnosed with MS.
I tried to understand it. "How? I mean, from what?"
"That's what I wanted to know," Erica said. "But who knows, man, who knows?" She threw her hands up. "I've read about it a lot, but it's like an X-file, this freaking thing. You wouldn't believe it."
"What are you gonna do?" I asked. We were all wondering. We wanted to hear that she would stay a part of our lives. "Can we do anything?"
"Nah, it's chilled out a lot. I feel okay. I think I'm just gonna keep on. It's crazy, huh?"
I breathed a small sigh of relief, but my classmates and I never really came down from it. Two years later I saw Erica at a medical conference and she looked radiant, with her athletic frame and her beautiful smile. And I still wondered how, from what? How could this be?
Multiple sclerosis is a prime example of medicine's rudimentary understanding of disease, a condition characterized by the dysfunction of nerves in the brain and body due to the degradation of their outer lining. As with many diseases that involve gradual loss of function in the nervous system, the cause is unknown and there is currently no cure. The classic medical school teaching about MS is that it is a condition "disseminated in time and space," meaning it's both temporally intermittent and symptomatically diverse it affects patients at different times in their lives, and also in different locations of their nervous system. MS typically develops slowly, exhibiting oddly disparate and changing symptoms, and so can be difficult to diagnose. The symptoms range from the mild, such as tingling of an arm, to the severe, including paralysis or loss of coordination. While many people with the disease live a long and somewhat uneventful (in terms of MS) life, some do not. Most individuals experience either mild symptoms or moderate to severe episodes periodically, but a small group experiences an unpredictable, progressive, and occasionally fatal deterioration.
While it's disturbing that we haven't yet established a prognostic marker, a cause, or a cure for MS, what really perplexes scientists is the strange set of patterns they've discovered in who contracts the disease. My colleague Erica was born near Bennington, Vermont, a quiet and beautiful New England town that like many other towns in the northern United States has become a virtual flash point for MS.
Why does Bennington have one of the highest MS rates in the world? We don't know, but we can read the maps that show it to be true. Studies of epidemiologic trends have established that the highest incidence of MS rests firmly at this latitude, 40 degrees or greater, throughout much of the industrialized world. If you're born in northern Wisconsin, or in the Scottish Highlands, or in New Zealand at latitude that's 40 degrees or more from the equator, your likelihood of developing MS is strikingly similar to that of people born in Bennington, Vermont.
The apparent consistency of this geographic mystery has been illustrated in studies time and time again. As if to prove that it's not a statistical anomaly or fluke, the incidence of MS also decreases consistently and incrementally as one's birthplace moves toward the equator. If Erica had been born in Florida instead of Vermont, her chance of developing MS would've been only one-quarter of what it was. However, had she been born in the state of Washington or Wisconsin (both about the same distance from the equator as Vermont), it would've been virtually the same.
Even stranger, had Erica moved to Florida as a young child she would've assimilated with the locals. That is to say, her chance of developing MS would've become roughly the same as that of those born in Florida. But if she had moved to Florida after adolescence (roughly age 15), her chance of developing MS would've remained the same as if she had never moved.
The epidemiology of MS is, as Erica said, a medical X-file, a total mystery. Potential geographic and atmospheric triggers including environmental toxins, intensity and duration of sunlight exposure, temperate viral and bacterial infections, temperature and humidity changes, diet, electromagnetic differences, and more have all been studied exhaustively. None of these factors appears to be independently associated with MS. In fact, new questions often arise from such studies. One finding is a strange exception to the latitude rule: for Alaskan native Inuits, regardless of latitude, diagnoses of MS are almost unheard of, or are at least extremely rare. There's no reasonable explanation for this, either.
As interesting and strange as these idiosyncrasies in the geography of MS may seem, the point that they illustrate is clearly more than a novelty. Erica was born in the northeastern portion of the United States, and I can assure you that every one of her physician friends has researched this mystery with a deep personal curiosity and a wish to discover something helpful or important, yet we could not, nor could the numerous other physicians or scientists devoting their time and work to this phenomenon. We remain hopelessly ignorant about why people get MS, and one product of our ignorance is that the only treatments for the disease are poorly developed and nonspecific.
While this epidemiologic puzzle highlights how much we have to learn about the complex disease of MS, there are basic issues encountered every day that perplex us equally. One of the great mysteries of modern medicine is one of our most ubiquitous and seemingly simplest nuisances back pain.
Sergeant Cole was a gunner normally posted in the turret of a Humvee, an aggressive and watchful sentinel protecting convoys throughout the Baghdad area for the United States Army. Outside of our emergency department, on dusty streets and forbidden highways, Cole wore sleek black shades and a quiet confidence. Built like a weight lifter and sporting shrapnel scars up and down his right arm, neck, and flank from his first tour in Iraq, the sergeant was admired on the base, known for razor-sharp vision and coolness under fire. As the reigning champion of the widely attended Friday Night Fights on the base, Cole was even something of a celebrity. He inspired knowing nods and crisp salutes from the enlisted, and he carried himself proudly.
Inside our emergency department, however, things were different. Ever since an awkward miss with a left hook in the boxing ring a month earlier, Cole had suffered from gripping back pain and spasms. On this day in late October he limped into the hospital tent squinting in pain, dropped his body armor on the floor, and hoisted himself onto one of the cots. He lay on his side and called weakly to the nurse.
"Ma'am, Major Z, I need a shot. Please."
Major Z looked at me over her glasses, and though it was the third time this week, I nodded. She opened the locked pharmacy box and drew out a syringe with narcotics in it.
"Doc, tell me what to do." Sergeant Cole stared at the side wall of the tent. "It's killing me up there." He was referring to being in the turret, semisquatting and semistanding for hours on end with forty pounds of equipment and protection strapped to his torso.
"Sergeant, your gunner days are over. We talked about this last time: I don't know what's going on in that back of yours, but I know it's time for you to take up something else. Something that won't tear you up or get you addicted to drugs. I'm going to talk to your commanding officer today."
"I went to physical therapy every day like you said. I took the pills you gave me. I did the exercises. Why's nothing working?"
I shook my head. "Don't know, Sergeant."
Cole nodded slowly, and his eyes welled up as the nurse injected his arm with morphine.
Musculoskeletal back pain pain arising from the muscles and bones of the back is one of the most common afflictions in the world. It's estimated that 70 percent of humans experience severe back pain at some point in their lives, and in the United States, this results in tens of thousands of surgeries each year. Healthy, fit, athletic people like Sergeant Cole get it as often as those who are physically unfit, but those whose backs and torsos are asked to carry uncommonly heavy loads are at exceptionally high risk.
As common as back pain is, however, physicians and researchers are mystified as to what causes it. At a cellular level, it's an enigma. Is it twisted muscle fibers? Irritated nerves? Involuntary spasms? No one knows. No research has ever taken a microscopic look at the muscle cells and fibers of someone having back pain and then compared them to identical cells and fibers from healthy individuals. Why has no one performed this study? For one thing, it's a tough study to find volunteers for we'd have to excise a chunk of their muscle to get the cells and fibers. For another, such a study may not even give us an answer.
What about using magnetic resonance imaging (MRI) to detect the cause of back pain? MRI, which is noninvasive and shows major muscle changes fairly well, continues to be the test of choice to evaluate back pain particularly to detect causes that are not muscular in origin, such as nerve compression and spinal cord problems. But there's a secret about MRIs and back pain: the most common problems physicians see on MRI and attribute to back pain herniated, ruptured, and bulging discs are seen almost as commonly on MRIs of healthy people without back pain. This means that herniated and bulging discs, and most of the other findings that radiologists report seeing on MRIs of the back, usually have nothing to do with back pain.
There are exceptions, of course, but herniated discs on an MRI most often are not an indication of a problem. They are a normal finding, suggesting that discs (the cartilage that cushions the area between the back bones) rupture, or herniate, with some frequency, and our bodies repair them uneventfully. Surgery to fix or remove a disc is usually performed in the hope that a herniated disc is compressing a nerve and causing the pain, but it carries a poor overall success rate. Even after the nerve is "decompressed," or freed, by removing the disc surgically, half of the time the patient's low back pain is unrelieved. This is likely because disc rupture and natural repair is common, an explanation that calls into question the widespread use of back surgery for ruptured discs. When I was in medical school a neurosurgeon once told me he didn't believe in back surgery. Given that we were scrubbing and prepping for a back surgery that he was about to perform, I found this slightly disconcerting. I asked why we were doing the surgery. He shrugged. "It's good practice."
The result of our ignorance about the actual pathology of back pain is that we have no cure for it. We can treat it with pain medicines, and we do, and they are temporarily effective. But we give people who have severe or chronic back pain the same medicine that we give to those who have knee or pancreas pain, or even cancer. And treating the pain doesn't mean that in a few days, weeks, months, or even hours, the pain won't come back. It usually does. Therefore Sergeant Cole suffered, and eventually had to give up his boxing and his gunning, because we were unable to help him. The existence of countless alternative fields that thrive on the treatment of back pain, including chiropractic medicine, acupuncture, and massage therapy, is due to medicine's failure to help back pain sufferers. Where alternative and complementary medicine has flourished, it's nearly always a sign of modern allopathic medicine's failure, and back pain is the prototype. While many well-intentioned, reputable, and effective physicians prescribe treatments or perform surgeries for back pain every day, the honest truth is that back pain is fraught with we-don't-know.
In his teachings to neophyte practitioners and students, Hippocrates cautioned physicians to "make no pretense to infallibility." As one might expect of a physician practicing in an age before the accurate elucidation of human function and disease, he was acutely aware of his lack of knowledge. Given this lack, his success as a physician and a physician-educator is mystifying. Despite subscribing to the "humors" theory of human health, despite knowing neither the location nor the function of the human heart, and despite being unaware of staple concepts like oxygen or the passage of blood through arteries and veins, Hippocrates was heralded as a man of medical science whom his patients and students loved, and whom the Western world lionized. How can someone with little to no true scientific knowledge still be seen as the great master of medical science?
There's a linguistic clue that may help to explain how a prescientific Hippocrates flourished in, and eventually led, the field of medicine. Those who've attempted to translate the Hippocratic writings for modern readers have often noted an idiosyncrasy in the language: the ancient Greeks made no distinction between "art" and "science." In Hippocrates, translator W. H. S. Jones notes in an introductory passage, "The word tešcnh can mean either 'art' or 'science,' though it inclines more towards the former." Discussing the evolution of ancient Greek language, he continues, "We have to wait until Aristotle...before there is a word approximately equivalent to our 'science' without any additional notion of 'art.'"
Hippocrates and his contemporaries believed the worlds of poetry, music, and medicine to be fundamentally intertwined. For ancient Greeks the scientist was philosopher and vice versa, as they envisioned their disciplines in a vastly different way than we envision our scientific models of thought and knowledge today. Hippocrates did not see the field of medicine as a storage bin of ultimately knowable facts and figures, and therefore he neither pretended nor aspired to be all-knowing. Instead, he knew his patients.
That doctors often don't have the answers they and their patients seek is a medical secret, the symptom of a quiet and pervasive deception. Physicians are frequently portrayed in popular media as all-knowing, and are often looked to for answers or expertise far beyond the reaches of our limited science and our narrow training. And yet a physician friend once told me that he learned during medical school that there are two things a doctor never says: "I don't know" and "I was wrong." That is a decidedly un-Hippocratic lesson. Peer behaviors, the examples of our mentors, and the general culture of medicine have all served to reinforce this lesson.
The public's misplaced faith that we have answers to all or even most questions may be flattering, but it has also been quietly corrosive. It takes a grounded understanding of medicine's limits to understand the true healing potential of a visit to the House of Medicine. Recognizing that we're incapable of curing or even understanding many conditions may allow patients to reclaim domain and personal control over their wellness, their illness, and their bodies.
The patient's abdication to the forces of modern medicine and technology is often undertaken with a false impression that there is high potential for cure, or that his physicians possess a detailed understanding of the pathways of his ailment. The truth is that in many cases, given the limits of our science, we don't. This reality only highlights the importance of patient opinions, views, and desires. Physicians are only, after all, consultants to the health of others. What we offer is our consultation and our limited expertise, in the hope that we can collaborate, that we can build a partnership. I tell friends that when a doctor says, "I don't know," it is rarely a sign of weakness or ignorance. More often it's a sign of a physician who knows and appreciates the limits of our science and is willing to be a partner. It's an olive branch of commiseration about what is not, and a hopeful readiness for what is.
Copyright © 2008 by David Newman