The Good Doctor

by Kenneth Brigham

  “Child Care Worker among Five Killed in Meningitis Outbreak Traced to Routine Back Pain Injections at Hospital . . . Amid Fears Thousands at Risk across 23 States,” Daily Mail, October 4, 2012.

  “New England Compounding Center Meningitis Outbreak,” Wikipedia, https://en.wikipedia.org/wiki/New_England_Compounding_Center_meningitis_outbreak.

  Gary Schwitzer, “Addressing Tensions When Popular Media and Evidence-Based Care Collide,” BMC Medical Informatics and Decision Making 13, suppl. 3 (2013): S3, doi: 10.1186/1472-6947-13-S3-S3.

  CHAPTER 14

  The Benefits of Ignorance

  Real knowledge is to know the extent of one’s ignorance.

  —CONFUCIUS162

  So this curious, constantly thinking doctor relies heavily on ignorance as she tries to figure out how the available evidence fits you personally. She is keenly aware of and intrigued by the fact that ignorance—the things nobody knows—is why we learn new things. There are always a few curious, daring, and adventurous souls who feel compelled to go off searching for the unknown answers, and sometimes what they find astounds us.

  This good doctor read somewhere in her youth that “a good question is worth a lot more than a mediocre fact,”163 and she took that dictum to heart. In fact, if her medical school teachers had a criticism of their star student, it would have been that she asked too many questions. Her common response to a pontificating professor was to ask why? Pontificating professors tend to be pretty satisfied with accepted dogma and don’t always respond well to a too inquisitive student. But this student persisted and even now all of the stuff that is either completely unknown or at best uncertain haunts and excites her. Excites her because she knows that ignorance drives discovery and discovery is the pulsating life blood of medicine. Discovery saves lives. The good doctor loves the lore of medical discovery and she often ponders those dramatic stories.

  A surgeon’s dissatisfaction with what he didn’t know changed a certain death sentence into a manageable disease. Leonard Thompson’s family doctor knew he had diabetes and that eating sugar was bad for him, but the doctor had no idea what caused the disease or what to do to prevent the young man’s premature death.164 A near starvation diet had kept him alive for a few years, but the fourteen-year-old was down to sixty-five pounds and drifting in and out of coma when he was admitted to the Toronto General Hospital in January of 1922. He was on his last legs. He would surely not leave the hospital alive.

  But a few years earlier, Frederick Banting, a little known Toronto orthopaedic surgeon, had been driven by what neither he nor anyone knew about diabetes to convince his department chairman to grubstake his effort to see whether maybe it had something to do with the pancreas.165 In a series of experiments in dogs, Banting and his medical student assistant, Charles Best, showed that something produced by the pancreas (they initially called it isletin since it came from nests of pancreas cells that looked like islets under the microscope) did indeed regulate blood sugar in dogs and cured their experimental diabetes.

  Leonard Thompson was selected as the first human to receive this new substance (now called insulin). The initial injection of an impure preparation helped some but also caused a severe allergic reaction. Injection of biochemist

  J. B. Collip’s pure preparation of the substance was begun on January 23, 1922, with stunning results. Leonard’s life was saved! A medical miracle! By 1923 the Eli Lilly Company was producing massive amounts of insulin, which has saved the lives of millions of diabetics over the years. What his doctors didn’t know about diabetes saved Leonard Thompson’s life and the lives of millions since.

  The diabetes story and others like it continue to inspire practitioners of medicine. But they aren’t just history lessons. Understanding that ignorance is a powerful source of life-saving discovery keeps the inquisitive doctor on the lookout for more recent examples. She finds examples because she looks for them but also because her curious mind is open to consider even the strangest possibilities. She knows the extent of her ignorance.

  Sometimes lives are saved by interventions that seem bizarre at first blush. University of Colorado surgeon Ben Eisman and his colleagues may have known in 1958 that millennia earlier, Chinese patients drank what they called “yellow soup” to treat intestinal ailments.166 But the Colorado group certainly did not know the cause of pseudomembranous colitis (it was later determined to be a really nasty bacterium, Clostridium difficile—C. diff), a serious disease that often didn’t respond very well to antibiotics. And they didn’t know what would happen if they infused fecal matter from a normal person into the lower intestine of patients with the disease. They knew, however, that their four patients, critically ill with this devastating disease, were not responding to conventional therapy and were likely to die unless they did something else. Hoping that some factor in the fecal material from a normal person would counteract whatever evil lurked in their patients’ bowels, in 1958 Eisman and his colleagues performed fecal matter transplants (FMT) in their four critically ill patients and reported the results in an article titled, “Fecal enema as an adjunct in the treatment of pseudomembranous colitis” in the journal Surgery. The results were dramatic. All four patients recovered from their colitis, their lives saved because their doctors were driven by what they didn’t know.

  Cheryl Cawthon’s (not her real name) doctor in Providence, Rhode Island, was near his wits end. Ms. Cawthon was a seventy-nine-year-old retired nurse. When she developed diverticulitis, an intestinal ailment resulting from infections of small outpouchings in the wall of the large bowel that occasionally occur with age, her doctor treated her with seriously strong antibiotics, the standard approach. Her diverticulitis resolved, but, as sometimes happens after treatment with potent antibiotics, Ms. Cawthon developed a persistent intestinal infection with C. diff that caused chronic debilitating diarrhea.167 Her doctor treated her now and again with a course of antibiotics, and she would get a little better for a while and then the diarrhea would return. Her doctor had no idea what to do next, but he did know that one of the faculty at a local university was doing some kind of unusual treatment and referred Ms. Cawthon there. The proposed treatment sounded strange, but also made some sense to the retired nurse. The idea was to overwhelm the pesky C. diff that had set up housekeeping in her bowel with a mass of bacteria that enabled the bowel to function normally, hoping the good guys would crowd out the bad guys. Which they did. Ms. Cawthon’s son dutifully agreed to donate the material to be transplanted and two days after the FMT Ms. Cawthon’s diarrhea disappeared, never to return. Another triumph of medical ignorance.

  A randomized study published in the New England Journal of Medicine in 2013 reported that FMT cured 94 percent of patients with C.diff infections while antibiotics only cured 31 percent. FMT was so successful that the controlled study was stopped early because it was felt unethical to withhold such an effective treatment from anyone with the disease.168 There are some reports that FMT may be beneficial in a number of other intestinal diseases that have been resistant to therapy. What doctors don’t know is the engine of discovery.

  The good doctor also knows from her personal experience and from stories of how major scientific discoveries were made that, as Yogi Berra is supposed to have said, “you can see a lot just by looking.” She looks intently at even the most common-place events because she knows it can pay off. She may know, for example, that biochemist Stan Cohen’s careful scrutiny of something simple that he didn’t expect wound up changing how we think about cancer and won him the Nobel Prize.169

  Since he worked with mice in his laboratory, no doubt Dr. Cohen knew that newborn mice don’t open their eyes until some days after birth, but he may not have known very much about the details of what happened after birth that allowed the pups’ eyes to open. Stan and Rita Levi-Montalcini, his colleague at Washington University, weren’t interested in why newborn mice’s eyes opened. They were
focused on factors that caused nerves to grow, and mouse salivary glands were rich sources of the nerve growth factor they were studying. However, when they injected crude salivary gland preparations into mice, Cohen noticed that the newborn pups’ eyelids opened ahead of schedule. A pure preparation of nerve growth factor didn’t have that effect. Something in the crude preparation was causing the eyelid skin (epidermis) to grow over the edges of the lids freeing the lids to open prematurely. Hmmm, a factor that stimulates epidermis to grow, Dr. Cohen must have thought; that’s interesting. He decided to find out what that factor was and published the discovery of epidermal growth factor in 1960. That discovery, based on a prescient observation of an unanticipated experimental side effect, has turned out to have major implications for cancer biology and potentially for cancer treatment.170 Dr. Cohen shared the 1986 Nobel Prize in Physiology or Medicine with Dr. Levi-Montalcini.171 Ignorance may or may not be bliss, but it is a powerful driver of discoveries that could save your life.

  Columbia University neuroscientist Stuart Firestein’s fascinating little book, Ignorance: How it Drives Science, resonates with any curious mind.172 Appalled at the discovery that most of his neuroscience students thought that their big textbook contained pretty much everything there was to know about the subject, Firestein began a course that he titled Ignorance, which became the stimulus for his book.

  Conventional teaching that knowledge drives out ignorance is, Firestein says, exactly 180 degrees at odds with the truth that knowledge produces ignorance. The more we know, the more we know that we don’t know. The bigger the island of knowledge, the longer the shoreline of ignorance. “The known is never safe,” Firestein writes. “The more exact the fact, the less reliable it is likely to be.” His description of how uncertainly science proceeds uses an unattributed proverb, “It is very difficult to find a black cat in a dark room. Especially when there is no cat.” The thinking doctor often feels like she is groping around in the dark trying to locate the black cat that may not exist, and she is perfectly willing to let you to know that.

  Like scientists in general, medical scientists are more excited by the unexpected than by proof of what they thought they already knew. We learn by being wrong. And medicine is very good at being wrong, which makes the field fascinating to a lot of bright and committed people. Some of those exceptional people are so taken with the uncertainties, the questions unanswered, that they dedicate their lives to efforts to discover. These are the clinician-scientists who are intrigued by the uncertainties but not satisfied with them. These are the bright and committed people who lies awake nights pondering unknowns and wondering what an unexpected result of an experiment is trying to say. The good doctor who practices medicine stays in touch with those people and will be sure that you benefit from their discoveries when the time comes.

  If ignorance is such a powerful stimulus for discovery, shouldn’t all doctors learn that in medical school? Perhaps they should, but too often they don’t. Medical education is particularly guilty of treating ignorance as the enemy, a dark force to be frightened away by the bright light of knowledge. Somewhere along the way, medical students often become convinced that they just need to know the facts with little appreciation for how those facts cower before the vastly greater power of ignorance. The process of training doctors as opposed to educating them can stifle curiosity, the innate fascination with the unknown. Too frequently doctors complete their training with no clear grasp of how important ignorance—a pervasive sense of maybe—is when dealing with the incredible complexity of human biology.

  There is some pretty convincing evidence that doctors in training aren’t learning how to deal with what they don’t know. Recognizing that effective clinical decisions require that the doctor “disclose personal uncertainty,” Professor of Family Medicine Christy Ledford and colleagues surveyed family practice training programs to determine “How We Teach U.S. Medical Students to Negotiate Uncertainty in Clinical Care,” the title of their publication in the journal Family Medicine.173 We would expect that family practice programs would do a better job of recognizing the need for teaching uncertainty than most other medical specialties. They probably do, but apparently they still don’t do it very well. Most of the program directors agree that teaching skills in dealing with uncertainty is important to do, but Ledford, et al. conclude that, “over half of all clerkships are missing an opportunity . . . to help learners develop competencies related to . . . uncertainty management, such as listening attentively, having a compassionate presence, and providing patient-centered communication.” Your good doctor learns this stuff on her own. Many of her peers do not.

  It is not a lot of consolation when you need a doctor to find out that being wrong is an essential part of medical practice and that a lot of practitioners don’t know how to deal with that. Uncertainty, that ubiquitous maybe, is always lurking in the wings so that decisions are always risky, whether or not the decision maker admits it.

  Granted that there is no font of absolute certainty in medicine, how can you best stack the deck in your favor? First, you can look on the bright side of maybe, see possibilities as the many good ways things could turn out. There is no doubt that your attitude toward your health has a potent effect, for better or worse. But that’s not enough. You also need a doctor whom you trust and who takes you on as the real person you are. But there are always risks and if you’re told otherwise, you’re not being dealt with honestly. So you’re not looking for a doctor who claims perfection; a doctor like that is going to be wrong and may not know it. You want a doctor who knows the risks and how to minimize them. That doctor knows the extent of her ignorance. She has long since made peace with uncertainty.

  “Confucius Quotes,” BrainyQuote, http://www.brainyquote.com/quotes/quotes/c/confucius101037.html.

  “Quotes and Anecdotes,” MA310, University of Kentucky, Spring 2001, http://www.ms.uky.edu/~lee/ma310sp01/anec.pdf.

  Howard Markel, “How a Boy Became the First to Beat Back Diabetes, PBS NEWSHOUR, January 11, 2013, http://www.pbs.org/newshour/rundown/how-a-dying-boy-became-the-first-to-beat-diabetes/.

  “The Discovery of Insulin,” https://www.nobelprize.org/prizes/medicine/1923/banting/biographical/.

  Claran Kelly, “Fecal Microbiota Transplantation—an Old Therapy Comes of Age,” New England Journal of Medicine 368 (2012): 474-475.

  Maryn McKenna, “Swapping Germs: Should Fecal Transplants Become Routine for Debilitating Diarrhea?” Scientific American, December 2011.

  Els van Nood, Anne Vrieze, Max Nieuwdorp, et al., “Duodenal Infusion of Donor Feces for Recurrent Clostridium Difficile,” New England Journal of Medicine 368 (2013): 407-415.

  Adam Navis, “Epidermal Growth Factor,” The Embryo Project Encyclopedia, http://embryo.asu.edu/pages/epidermal-growth-factor.

  John Mendelsohn, “Targeting the Epidermal Growth Factor Receptor for Cancer Therapy,” Journal of Clinical Oncology 20, suppl. 1 (2002): 1-13.

  Stanley Cohen, “Nobel Lecture—Epidermal Growth Factor,” Bioscience Reports 6 (1986): 1017-1028, 1086.

  Stuart Firestein, Ignorance: How it Drives Science (Oxford: Oxford University Press, 2012).

  Christy Ledford, Dean Seehusen, Alexander Chessman, and Navkrian Shokar, “How We Teach Us Medical Students to Negotiate Uncertainty in Clinical Care: A Cera Study,” Family Medicine 47 (2015): 31-36.

  CHAPTER 15

  The Laying On of Hands

  It is believed by experienced doctors that the heat which oozes out of the hand, on being applied to the sick, is highly salutary.

  —HIPPOCRATES, fifth century BC174

  The thoughtful, caring doctor will touch you with her hands. She will do that for three reasons: to sense what’s going on inside; to connect with who you are; and because she is a healer.

 
TO SENSE WHAT’S GOING ON INSIDE

  Medical students take a course called Physical Diagnosis which is supposed to teach them how to use their senses to detect clues to how well a patient’s vital organs are doing their jobs. There are four parts to the physical examination: inspection (looking carefully at the body’s color, contours, and other features that can be seen with the naked eye); percussion (thumping on the chest, abdomen, etc. and registering both the sound and the feel of the response); palpation (poking and prodding all of the relevant areas to determine size, contour, and sensitivity of the patient’s internal organs); and finally auscultation (exploring each body area with a stethoscope, listening carefully for normal and abnormal sounds and registering which organs seem to be producing them). There was a time when this was the most important course in the education of an aspiring doctor.

  So when you go to the doctor you can confidently expect to be looked at, thumped on, poked, prodded, and listened to, right? Well, you shouldn’t get your hopes up. While those things are true if you’re seeing the kind of doctor we are describing, she may be in the minority these days. After all, now that we have x-rays, ultrasound, CAT scans, MRIs, and all those other technologies that see what’s going on inside with considerable precision, why does the doctor need to master an approach as low tech as the traditional physical exam? A lot of doctors just don’t see the point. Famed Harvard cardiologist Roman DeSanctis jokingly lamented, “If you come to our hospital missing a finger, no one will believe you until we get a CAT scan, an MRI, and an orthopedic consult. We just don’t trust our senses.”175

  And machines can only see what the doctor tells them to look for. Depending on where they’re looking and how, even the most sophisticated technologies can miss a diagnosis that is readily made by a careful physical exam, which has serious implications for therapy.