What Makes a Great Physician?

At this blog’s inception nearly five years ago, I asked myself the following question: “When you watch impressive doctors at work,
what is it that most impresses you?” In other words, what makes a great
physician? I was a third-year medical student at the time and I couldn’t
answer the question. At the beginning of training one can hardly keep up
with the incoming information, let alone consider the characteristics that
make a great physician. I liked and disliked certain doctors depending on
the way they treated residents, medical students, or patients. But beyond
kindness, their traits varied widely. During residency I have been
fortunate to work with many admirable doctors, and consequently my sample
size has grown. Seeing what I’ve seen thus far, I think
curiosity and humility are the two most impressive characteristics of a
great physician.

Wikimedia

Galen of Pergamum (AD 129–ca. 216), the Greco-Roman doctor, wrote extensively about how to
make physicians great again in his treatise That the Best Physician Is Also a Philosopher. He bemoans the lost art of medicine and the
corruption of the profession. He advocates for a temperate lifestyle,
arguing that if a physician puts virtue above wealth, he or she will be
“extremely hardworking” and will therefore have to avoid “continually eating or drinking or indulging in sex.”

A doctor must also be “a
companion of truth.” “Furthermore, he must study logical method to know how
many diseases there are, by species and by genus, and how, in each case, one
is to find out what kind of treatment is indicated.”

He continues,

So as to test from his own experience what he has
learnt from reading, he will at all costs have to make a personal
inspection of different cities: those that lie in southerly or northerly
areas, or in the land of the rising or of the setting sun. He must visit
cities that are located in valleys as well as those on heights, and cities
that use water brought in from outside as well as those that use spring
water or rainwater, or water from standing lakes or rivers.

Notice that Galen does not endorse brilliance as a required characteristic of a
physician. No, he advocates for the intelligent use of one’s faculties.
Indeed, he seems to favor curiosity about the surrounding world as a
necessary quality for a doctor.

Curiosity, a desire to discover and a desire to know, is inseparable from a
great physician. In residency we are often told by our attending physicians
that we must be “lifelong learners.” Curiosity naturally creates lifelong
learners. Medicine, after all, is not confined to what one learns in
medical school or residency. If it were, our doctors would not be very
good. One does not see every disease process in residency, one often
forgets certain things, and

the evidence

and guidelines are forever changing and improving. Thus, we must always be
looking up the latest evidence on the diseases we see.

Moreover, there isn’t always a clear diagnosis or treatment, and
physicians must scour scientific literature for the answer. When, as so
often happens, there is a diagnostic mystery, curiosity works against our
inclination towards laziness and forces us to stay on our toes, question
what we believe and why we believe it.

Curiosity also aids the clinician-researcher. Physicians since Galen’s time
have participated in various forms of research, attempting to answer
questions that have not yet been answered. For many of our predecessors
the questions were quite basic, given the general ignorance about the world
of biology. Yet there are still vast areas of medicine for which answers
are needed. The most obvious examples in the specialty of neurology concern
brain tumors or diseases like

Parkinson’s
. The lifespan for patients with certain brain tumors is a year and a half
– how does one improve treatments for these virulent neoplasms? For
Parkinson’s disease, we can only treat symptoms but cannot slow the disease
down – what treatments might reverse this pathology or at least stop it in
its tracks? Curiosity drives physician-researchers to make discoveries and
to seek answers to these questions.

But there is another characteristic, too, necessary in order to be a great
physician. The sheer volume of material one must know and understand about
medicine as well as the natural world is enormous and infinite. Because of the infinite knowledge they cannot possibly possess,
doctors must also confront this world with humility, humility about how
much one must truly know and understand in order to be great.

What was true in Galen’s life is doubly true today: There is a vast world of knowledge
in the realm of medicine. Humility, like curiosity, provides doctors with a
sense of the struggle to accumulate a vast amount of knowledge.
It helps them confront the possibility of being wrong. And
as I’ve written on this blog,

doctors are often wrong
. Humility makes us more likely to double-check ourselves, to re-examine
the patient when we’re unsure, to look things up when we feel insecure in
our diagnosis. It makes us more thorough. It urges us to listen to the
opinions of other doctors, of nurses, or even of patients.

What, then, when I watch doctors at work, most impresses me? What, then,
makes a great physician? Curiosity and humility are necessary
characteristics. There is not a single physician I look up to who does not
have both of these qualities. These alone may not be sufficient but I have
also noticed that other remarkable characteristics tend to accompany
curiosity and humility: kindness, self-discipline, intellectual rigor,
equanimity.

William Osler
Wikimedia

In his valedictory address to the University of Pennsylvania School of Medicine in 1889
(also known as the essay Aequanimitas) Dr. William Osler, one of the original four physicians at Johns Hopkins Hospital and a
legendary professor of medicine at the Hopkins medical school and later at
Oxford, discusses the quality that he thinks is most integral to being a
physician – imperturbability or equanimity. He writes:

A distressing feature in the life which you are about to enter, a feature
which will press hardly upon the finer spirits among you and ruffle their
equanimity, is the uncertainty which pertains not alone to our science and
arts but to the very hopes and fears which make us men. In seeking absolute
truth we aim at the unattainable, and must be content with finding broken
portions.

What lies behind Osler’s idea of equanimity is an acknowledgement of
uncertainty in medicine. And such an acceptance arises first from a humble
and inquisitive outlook. Curiosity and humility acknowledge this
uncertainty and the need to prepare for it, with equanimity.

The Face and the Person

I carry the plenum of proof, and everything else, in my face.

Walt Whitman, Leaves of Grass

The importance of the face in human interactions from the day we are born
cannot be overstated.

Infants, even if they are blind, communicate their feelings to
their parents in large part through facial expressions. For children and adults, so much of what we comprehend about people’s feelings
involves interpreting a glance, a smirk, or raised eyebrows. And there has been research suggesting that our own facial expressions can affect how we feel — what is called the “facial feedback hypothesis.”

I didn’t fully understand the importance of facial communication, though,
until I met patients with illnesses — such as

Parkinson’s Disease
 (PD),

depression
, and

schizophrenia
 — that drastically alter a person’s ability to express thoughts and feelings
through small movements of facial muscles. When meeting patients afflicted in this manner, I don’t know how
they receive my questions or explanations. I don’t know if they’re upset. I
can’t tell what they’re going to say next. The emotionless face, so empty
and devoid of character, can be frightening; a person
seemingly unaffected by emotion is capable of almost anything. Of course, these
patients experience emotions of all kinds. Their faces just don’t exhibit
them.

Leon Kass writes in Toward a More Natural Science about the
importance of emotions expressed through the face, for instance in blushing. This can help us to think about patients with
limited facial communication.

Blushing, like many facial expressions, “is not under our control.” Moreover, blushing is the “involuntary outward bodily manifestation of a very
complex psychophysical phenomenon.” Mental states induce blushing: shyness,
modesty, embarrassment, shame. Many of us blush when we’ve done something
wrong, know we’ve done something wrong, and are scolded for doing so. It is,
in certain respects, a public proclamation of shame. Similarly, the
furrowing of the brow, a smile, and a frown are also public manifestations of
mental states. All
this indicates that we are social beings and cognizant of those
around us. To wit, Kass argues that blushing requires a notion of the self,
a concern of how one appears to others, and an “awareness that one is on
display.”

The same is not always true about every facial expression, but
it is certainly applicable in most circumstances. When we laugh at someone
else’s joke, or cry when wronged in some way, we can do so alone. But more
frequently we do so in front of others and in response to others. In the
case of crying, we may try to be alone when we sob because we are concerned
about appearing fragile or weak. With smiling or laughing, we are
recognizing that someone else said something funny. These are social
reactions that require cognizance or acknowledgement of other human beings, and many of our facial expressions take place within the context of
social relationships. “The face,” Kass writes, “is not only the organ of
self-expression and self-presentation, the source of our voice and
transmitter of our moods; it also contains the chief organs for beholding
other selves.”

Because of the significance of the face in our social interactions, it is
“most highly regarded, both in the sense of most looked at and in
the sense of most esteemed.” Attention, wanted and unwanted, centers on the
face. Yes, some superficial aspects of ourselves can reveal much
beneath the surface: our deepest worries, fears, and joys. Such an
understanding ought to give us new appreciation for the kinds of
difficulties patients without facial expressions confront. They are
handicapped in their interactions with others. They inadvertently block a
vital mode of communication. They cannot indicate how they feel without
using words. As physicians we treat the symptomatic aspects of diseases
like Parkinson’s, but we cannot change someone’s face; even while patients
are on their PD medications, their facial deficits persist. It is one of
those debilitating aspects of illness that one can easily forget when thinking about people who suffer from these illnesses but that one cannot ignore when facing them in person.

Should Computers Replace Physicians?

In 2012, at the Health Innovation Summit in San Francisco, Vinod Khosla, Sun Microsystems co-founder and venture capitalist, declared: “Health care is like witchcraft and just based on
tradition.” Biased and fallible physicians, he continued, don’t use enough science or data — and thus machines will someday rightly replace 80 percent of doctors. Earlier that same year, Khosla had penned an article for TechCrunch in which he had made a similar point.
With the capacity to store and analyze every single biological detail, computers would soon outperform human doctors. He writes, “there are three thousand or more metabolic pathways, I was once told, in the human body and they
impact each other in very complex ways. These tasks are perfect for a computer to model as ‘systems biology’ researchers are trying to do.” In Khosla’s
vision of the future, by around 2022 he expects he will “be able to ask Siri’s great great grandchild (Version 9.0?) for an opinion far more accurate than the one I get
today from the average physician.” In May 2014,

Khosla reiterated his assertion that computers will replace most doctors
. “Humans are not good when 500 variables affect a disease. We can handle three to five to seven, maybe,” he said. “We are guided too much by opinions, not by
statistical science.”

The dream of replacing doctors with advanced artificial intelligence is unsurprising, as talk of robots replacing human workers in various fields — from eldercare to taxi driving — has become common. But is Vinod Khosla right about medicine? Will we soon
walk into clinics and be seen by robot diagnosticians who will cull our health information, evaluate our symptoms, and prescribe a treatment? Whether or not the technology will exist is difficult to predict, but we are certainly on our way there. The IBM
supercomputer Watson is already being used in some hospitals to help diagnose cancer and recommend treatment, which it does by sifting through millions of patient records and producing treatment options based on previous outcomes. Analysts at Memorial Sloan Kettering Cancer Center are training Watson “to extract and interpret
physician notes, lab results, and clinical research.” All this is awe-inspiring. Let us generously assume, then, for a moment, that the technology for Khosla’s future will be
available and that all knowledge about and treatment options for medical problems will be readily analyzable by a computer within the next decade or so. If this is the future, why
shouldn’t physicians be replaced?

There are several errors in Khosla’s way of thinking about this issue. First of all, modern health care is not “like witchcraft.” Academic
physicians, for example, use evidence-based medicine whenever it is available.
And when it isn’t, then they try to reason through a problem using what biologists know about disease presentation, physiology, and pharmacology.

Moreover, Khosla mischaracterizes the doctor-patient interaction. For Khosla, a visit to the doctor involves “friendly banter” and questions about symptoms. The
doctor then assesses these symptoms, “hunts around … for clues as to their source, provides the diagnosis, writes a prescription, and sends you off.” In Khosla’s estimation the entire
visit “should take no more than 15 minutes and usually takes probably less than that.” But the kind of visit Khosla writes about is an urgent care visit wherein quick and minor issues are addressed: strep throat or a small laceration requiring a
stitch or two. Yes, these visits can take fifteen minutes, but so much of medicine does not involve these brief interactions. Consider the diabetic
patient who has poorly controlled blood sugars, putting her at risk for stroke, heart attack, peripheral nerve destruction, and kidney failure, but who hasn’t
been taking her medications. Or consider a patient addicted to cigarettes or on the verge of alcoholism. Consider the patient with Parkinson’s disease who wonders how this new diagnosis
will affect his life. And what about the worried parents who want antibiotics for their child even though their child has a viral infection and not a
bacterial infection? I can go on and on with scenarios like these, which occur hourly, if not daily, in nearly every medical specialty. In fact,
fifteen-minute visits are the exception to the kind of medicine most physicians need to practice. One cannot convince an alcoholic to give up alcohol, get
a diabetic patient to take her medications, or teach a Spanish-speaking patient to take his pills correctly in fifteen minutes. In addition, all this is impossible without “friendly banter.”

As Dr. Danielle Ofri, an associate professor of medicine at the New York University School of Medicine,

wrote in a New York Times blog post, compliance with blood pressure medications or diabetic medications is extremely difficult, involving multiple factors:

Besides obtaining five prescriptions and getting to the pharmacy to fill them (and that’s assuming no hassles with the insurance company, and that the
patient actually has insurance), the patient would also be expected to cut down on salt and fat at each meal, exercise three or four times per week, make
it to doctors’ appointments, get blood tests before each appointment, check blood sugar, get flu shots — on top of remembering to take the morning pills
and then the evening pills each and every day.

Added up, that’s more than 3,000 behaviors to attend to, each year, to be truly adherent to all of the
doctor’s recommendations.

Because of the difficulties involved in getting a patient to comply with a complex treatment plan, Dr. John Steiner argues in an article in the Annals of Internal Medicine that in
order to be effective we must address individual, social, and environmental factors:

Counseling with a trusted clinician needs to be complemented by outreach interventions and removal of structural and organizational barriers. …[F]ront-line clinicians, interdisciplinary teams, organizational leaders, and policymakers will need to coordinate efforts in
ways that exemplify the underlying principles of health care reform.

Therefore, the interaction between physician and patient cannot be dispensed with in fifteen minutes. No, the relationship involves, at minimum, a
negotiation between what the doctor thinks is right and what the patient is capable of and wants. To use the example of the diabetic patient, perhaps the
first step is to get the patient to give up soda for water, which will help lower blood sugars, or to start walking instead of driving, or taking the
stairs instead of the elevator. We make small suggestions and patients make small compromises in order to change for the better — a negotiation that helps
patients improve in a way that is admittedly slow, but necessarily slow. This requires the kind of give-and-take that we naturally have in relationships with other people, but not with computers.

This kind of interaction also necessitates trust — trust regarding illicit drugs, alcohol, tobacco, and sexual activity, all of which can contribute to or
cause certain medical problems. And a computer may ask the questions but cannot earn a patient’s confidence. After all, these kinds of secrets can only be
exchanged between two human beings. David Eagleman, a neuroscientist at the Baylor College of Medicine, writes in his book Incognito that when we reveal a secret, we almost always feel that “the receiver of the secrets
has to be human.” He wonders why, for example, “telling a wall, a lizard or a goat your secrets is much less satisfying.” As patients, we long for that human reception
and understanding that a physician can provide and use to our advantage in coming up with a diagnosis.

Khosla neglects other elements of medical care, too. Implicit in his comments is the idea that the
patient is a consumer and the doctor a salesman. In this setting, the patient buys health in the same way that he or she buys corn on the cob. One doesn’t need friendly banter or a packet of paperwork to get the best corn, only a short visit to the
grocery store.

And yet, issues of health are far more serious than buying produce. Let’s take the example of a mother who brings her child in for ADHD medication, a
scenario I’ve seen multiple times. “My child has ADHD,” she says. “He needs Ritalin to help his symptoms.” In a consumer-provider scenario, the doctor gives the
mother Ritalin. This is what she wants; she is paying for the visit; the customer is king. But someone must explain to the mother what ADHD
is and whether her child actually has this disorder. There must be a conversation about the diagnosis, the medication, and its side effects, because the consequences of these are lifelong. Machines would have to be more than just clerks. In many instances, they would have to convince the parent that, perhaps, her child does not have
ADHD; that she should hold off on medications and schedule a follow-up to see how the child is doing. Because the exchange of goods in
medicine is so unique, consequential, and rife with emotion, it is not just a consumer-cashier relationship. Thus computers, no matter how
efficient, are ill-fitted to this task.

Khosla also misunderstands certain treatments, which are directly based on human interactions. Take psychiatry for example. We know that

cognitive behavioral therapy and medication combined are the best treatment for a disease like depression
. And cognitive behavioral therapy has at its core the relationship between the
psychiatrist or therapist and the patient, who together work through a depressed patient’s illness during therapy sessions. In cognitive behavioral therapy, private
aspects of life are discussed and comfort is offered — human expressions and emotions are critical for this mode of treatment.


To be sure, Khosla is right about quite a lot. Yes, technology ought to make certain aspects of the patient visit more efficient. Our vital signs may one day easily be taken with the help of our mobile phones, as he suggests, which
would save time checking in to a clinic and could help give physicians constant and accurate measurements of blood pressure in hypertensive patients or EKG
recordings in patients with heart disease. Technology of this sort could also indicate when an emergency is happening or how a patient ought to alter medication
doses.
Furthermore, Khosla correctly identifies some of the limitations of human physicians: “We cannot expect our doctor to be able to remember everything from medical
school twenty years ago or memorize the whole Physicians Desk Reference (PDR) and to know everything from the latest research, and so on and so forth.”
True, the amount of information accumulated by modern medical research is beyond the capability of any human being to know, and doctors do make mistakes because they forget or are not up on the latest research. In a 2002 study in the Journal of Neurology, Neurosurgery and Psychiatry, investigators found that 15 percent of patients with a diagnosis of Parkinson’s disease do not
necessarily fulfill criteria for the disease and 20 percent of patients with Parkinson’s disease who have already seen medical providers have not been diagnosed.
These are large percentages that have profound implications for people’s lives. And this is exactly why physicians must use technologies like Watson to do a
better job, not necessarily abdicate the job altogether. Most of us already carry smartphones or tablets on rounds, to look up disease processes or confirm
our choice of antibiotic.
Lastly, Khosla wisely points out that physician bias can negatively affect a patient’s treatment. As he writes, “a physician’s bias makes all these
personal decisions for patients in a majority of the cases without the patient (or sometimes even the physician) realizing what ‘preferences’ are being
incorporated into their recommendations. The situation gets worse the less educated or economically less well-off the patient is, such as in developing
countries, in my estimation.” Undoubtedly, this dilemma is real. I have spent many of my posts on this blog writing about the issue of remaining unbiased or level-headed in the face of difficult patient interactions.
study published in Obesity in 2013 found that physicians “demonstrated less emotional rapport with overweight and obese patients … than for normal weight patients,” which may
“weaken the patient-physician relationship, diminish patients’ adherence to recommendations, and decrease the effectiveness of behavior change counseling.”
And

as Tara Parker-Pope remarks in the New York Times
, “studies show that patients are far more likely to follow a doctor’s advice and to have a better health outcome when they believe their doctor empathizes
with their plight.” If bias exists in lieu of empathy, it makes sense that patients have worse outcomes. What makes doctors most valuable,
their humanity, can have negative consequences.
But people can learn from studies, alter their behavior, and remain human. Computers or robots can learn from studies and alter their behavior, but they will
always be robots. They will never earn the trust of the chronically ill drug addict. They will never be able to negotiate with the most difficult patients
who demand specific treatments but may not be entirely sure why. An ideal system would not be one built solely on fallible human doctors but one
in which new tools significantly augment human physicians’ skill and knowledge. A measured combination of these will put all the information at a doctor’s
fingertips while keeping the art of medicine alive.

Becoming Cynical, Part 4

I have written quite a bit about why physicians become cynical (see herehere, and here). What follows are some more thoughts on this topic
that relate to my previous post on Parkinson’s Disease (PD).

Recently, a sixty-three-year-old patient came to the neurology clinic for a left-handed tremor that had become worse. He and his wife gave a classic history of the
onset of PD. His tremor occurred only at rest. He felt his left arm was weaker than his right arm — this was evident in some sessions with his personal trainer. He noticed his handwriting had become slightly smaller. And his wife said she couldn’t hear him well anymore.
She initially thought it was due to her own hearing loss, but her friends also found that his voice had become harder to hear. The attending physician and I asked other questions
regarding sleep (sometimes PD patients act out their dreams), drooling, and cognitive status. After a physical exam, a cognitive test, and some more
questioning, the attending physician concluded that the patient had PD.

At this point in my short career I had seen multiple patients with PD, some in its early stages, some advanced, and some in-between.
I was at least superficially familiar with the course of the disease. So when we broke the news to the patient and his wife, it felt slightly banal:
another PD patient, another diagnosis, and another prescription for PD drugs.

Shutterstock

But this patient’s reaction took me by surprise. Most people are upset, ask for some information about the disease, take
their prescriptions and leave. But in this case, the patient’s questions were far more detailed than I was used to (the attending, given the extent of
his experience and knowledge knew exactly what to say). The conversation eventually led to a discussion about the advanced stage of the disease. We explained
that medications and deep brain stimulation would become less and less effective. Ultimately, he would get dyskinesias and end up in a wheelchair.

We all know we’re going to die — that is one of the few things in medicine that one can say is 100 percent certain. But there is something eerie about hearing
exactly how you’re guaranteed to deteriorate. The attending was telling the patient in a very diplomatic way that his life would look just so in about twenty
years. It was said gently, but the patient understood the meaning well. His wife began to cry and he teared up, too. His movements, his hobbies, and control
would slowly peter out and vanish.

After I told this story to someone with experience in the medical field, the person responded with, “I don’t know what they’re so upset about — it’s just
Parkinson’s Disease.” This probably seems callous and insensitive. Just PD? Think of the horrible symptoms, the side effects of the medications, the
creeping debilitation. Imagine, eventually, being locked-in, frozen and unable to move, relying on a pill that becomes less and less effective for allowing such simple functions as turning
around or walking. It is indeed a terrible disease.

But for a physician who has seen far worse — such as ALSCreutzfelt-Jakob diseasetrauma, Sudden Infant Death Syndrome (SIDS), all of which involve rapid debilitation and death — PD can seem preferable, with its long course and all the available treatments, however limited they may be.

This tendency to compare the severity of varying illnesses is perhaps one of the greatest traps in practicing medicine. Physicians see so much that
diseases that are serious to most patients seem mild relative to the more horrifying ones. I have found myself falling into this pit more than once. I remember
doing CPR on a patient who had burst a pulmonary artery (a major artery in her lungs) as a complication of her lung cancer. As I did chest compressions, blood poured out of her mouth and onto my pants, soaking my shoes and scrubs. While this was going on, I got
a call from a nurse about a patient with a history of drug abuse who wanted more pain medication. He may very well have been in serious pain. But compare
his needs to this woman’s death. Clearly, one was much more affecting, disconcerting, and significant than the other, and it was a while before I
could address the drug patient’s pain appropriately. It can be all too easy to dismiss as a “mild” disease or complaint the sorts of conditions against which our exposure has hardened us.

Thus, with experience, our expectations change; it takes more to move us. We shrug off the majority of hospital cases as “not that bad” or “benign.” I think
all this is inevitable in a career in medicine. One must pinch oneself every day, at the very least, to recognize it.

The Parkinson’s Patient

In 1817, Dr. James Parkinson, an English surgeon, scientist, and political activist, wrote in An Essay on the Shaking Palsy about a new medical pathology. In this work, he
describes the characteristics of what would later be called Parkinson’s Disease (PD). The essay is worth
examining because it offers a perspective on a disease that we see quite often — PD is one of the most common debilitating neurologic disorders
today, affecting about 1 percent of people over sixty.

Parkinson set out to characterize the illness by doing what a scientist ought to do, observing and taking notes:

The disease is of long duration: to connect, therefore, the symptoms which occur in its later stages with those which mark its commencement, requires a
continuance of observation of the same case, or at least a correct history of its symptoms, even for several years.

The onset of PD is extremely subtle; its initial symptoms are “slight and nearly imperceptible.” Nevertheless, patients generally experience a sense of
weakness and a minor unilateral hand tremor at rest (the typical tremor is exhibited in this video). Soon, “the morbid influence is felt in some other part,” perhaps the leg on the side
of the affected hand. Other symptoms arise over months to years, too, making precise manipulation, for instance when writing, more challenging:

As the disease proceeds, similar employments are accomplished with considerable difficulty, the hand failing to answer with exactness to the dictates of
the will. Walking becomes a task which cannot be performed without considerable attention. The legs are not raised to that height, or with that promptitude
which the will directs, so that the utmost care is necessary to prevent frequent falls.

In addition to falling frequently, patients’ handwriting shrinks in size (this is known as micrographia); they experience difficulty sleeping and increased severity of
tremors (eventually affecting both hands and both legs); the disease even alters speech, causing patients to speak softly (hypophonia); and uncontrolled drooling occurs along with increased muscle rigidity. Patients often feel
frozen in space, trapped by the inability of their muscles to obey their commands.

Parkinson describes the last stages of the disease as follows:

The chin is now almost immoveably bent down upon the sternum. The slops with which he is attempted to be fed, with the saliva, are continually trickling
from the mouth. The power of articulation is lost. The urine and fæces are passed involuntarily; and at the last, constant sleepiness, with slight
delirium, and other marks of extreme exhaustion, announce the wished-for release.

And yet, despite Parkinson’s detailed knowledge of the disease course, there was no real indication as to the etiology or pathology of it. One can sense Parkinson’s frustration with the ignorance of the scientific community:

We are in fact as little informed respecting the nature of the affection, inducing the carious state of the vertebræ, as we are respecting the peculiar
change of structure which takes place in this disease. Equally uninformed are we also as to the peculiar kind of morbid action, which takes place in the
ligaments of the joints; as well as that which takes place in different instances of deep seated pains and affections of the parts contained in the head,
thorax, and abdomen….

As for “the means of cure,” Parkinson writes, “nothing direct and satisfactory has been obtained.” Indeed, he proposed a treatment that seems absolutely
bizarre to us today: drain blood from the upper part of the neck. One theory held that the disease came from irritation of the theca, a covering of the spinal cord, leading to inflammation and pressure. According to Parkinson,
draining the blood could release that pressure and mitigate symptoms.

Though this treatment amounted to very little, Parkinson does conclude his work with some hope:

There appears to be sufficient reason for hoping that some remedial process may ere long be discovered, by which, at least, the progress of the disease may
be stopped. It seldom happens that the agitation extends beyond the arms within the first two years; which period, therefore, if we were disposed to divide
the disease into stages, might be said to comprise the first stage. In this period, it is very probable, that remedial means might be employed with
success: and even, if unfortunately deferred to a later period, they might then arrest the farther progress of the disease, although the removing of the
effects already produced, might be hardly to be expected.

*     *     *

Looking back at Parkinson’s essay with today’s knowledge about the disease, we can say that his descriptions are unusually accurate for a medical text that is two centuries old. In fact, many of the
patients I’ve seen in clinic today with Parkinson’s disease have stories identical to those described by Parkinson. However, there are a few corrections
that we need to make. First, Parkinson neglects to mention the dramatic changes in facial expressions among these patients — a practiced observer can pick out a PD patient
merely by making eye contact.

I saw a seventy-year-old female in clinic with a new diagnosis of the disease. She had the classic hand tremor and muscle rigidity, but I
remember her face the most. It was haunting. She rarely blinked and stared with the utmost intensity, not quite sure when to look away. That small social
grace of breaking eye contact had been lost. The eyes peered, not vapidly, but creepily. They challenged you to speak or break the stare. The whole face
seemed devoid of a crucial aspect of its human expressiveness. I noticed no smile or frown even when I joked around with her. Her expressions contained a strange mixture of repressed
anger and stoicism. Facial signals, emotions, and features are dampened and even nonexistent in PD to a frightening extent. And imagine the emotional pain
that comes with the knowledge that your face publicly separates you from everyone else.

Parkinson also did not know anything about the pathology of the disease. We now understand that the disease can be linked to the death of neurons. Specifically, neurons that release dopamine in the brain in the substantia nigra die off, leading to an overall reduction in dopamine in the brain. The disease
causes symptoms after 80 percent of these dopamine-producing neurons are lost. Why this happens is still unclear — approximately 85 to 90 percent of the cases are idiopathic
(meaning the cause is unknown) and 10 to 15 percent of affected patients have a first-degree relative with the disease (and we’ve identified at least some of the genes that are associated with PD). But there
are interesting non-genetic factors that contribute to the risk for developing the disease. Pesticide exposure and the drinking of well water have been linked to PD (see for instance chapter 77 of the textbook Neurology of Movement Disorders by Haq, Foote, and Okun). And the use of tobacco, bizarrely, has been
inversely associated with risk for the disease.

Thankfully, though, the treatments for PD have improved tremendously over the last few decades. Dopamine agonists and medications like carbidopa-levodopa stimulate
dopaminergic receptors in the brain, freeing patients from their feelings of bradykinesia (slow movement) and rigidity. One patient I spoke with called his
medications “a miracle.”

Deep Brain Stimulation
(DBS) also dramatically improves patient’s symptoms. Neurosurgeons implant a thin electrical wire either in the globus pallidus internus or the subthalamic nucleus — two different parts of the brain — which then connects to a pulse
generator. This generator sends electric pulses into the brain, and symptoms can change almost immediately. I clearly recall my first encounter with a patient who received DBS. In the
exam room, the attending physician increased the voltage going through the generator and the patient’s tremor gradually
decreased until it disappeared. It was absolutely incredible to witness.

There are, of course, side effects to these medications and procedures. Impulsivity is one that I have had a particular interest in: patients on dopamine
agonists and with DBS can take up gambling, excessive shopping or risky sexual activity. Additionally, the medications can cause nausea, vomiting,
dizziness, hallucinations, and constipation. The most serious side effects of a drug like carbidopa-levodopa are dyskinesias, which occur after long-term use. Dyskinesias are involuntary movements: patients writhe sometimes fluidly and sometimes suddenly. An arm shoots up in the air and is forcefully pushed down into
one’s lap; the tongue hangs out of the patient’s mouth and licks the upper and lower lips; the lips smack together uncontrollably; legs kick. The patient
seems to be possessed. Since these are uncontrollable, patients are not only forced to do things they don’t desire but are also faced with
the stigma of their unusual behavior when they leave the home.

Dr. Oliver Sacks, the late neurologist, writer, and professor at NYU, describes one unusual method of dealing with parkinsonian symptoms in his book, Musicophilia. He observes the fascinating, rare, and still mysterious response a particular patient had to
playing music:

If one walked her down the hallway, she would walk in a passive, wooden way, with her finger still stuck to her spectacles…. As soon as she sat down on the
piano bench, her stuck hand came down to the keyboard, and she would play with ease and fluency, her face (usually frozen in an inexpressive parkinsonian “mask”) full of expression and feeling. Music liberated her from her parkinsonism for a time — and not only playing music, but imagining it.
Rosalie knew all of Chopin by heart, and we had only to say “Opus 49” to see her whole body, posture, and expression change, her parkinsonism vanishing as
the F-minor Fantasie played itself in her mind.

Even with all these treatment options, nothing halts the progression of the disease. Many patients I have met in the neurology clinic have had PD for
almost twenty years, and their symptoms severely affect their lives. They have dyskinesias; their medications last for a much shorter period of time than
they did years ago; they use a wheelchair; some of their voices barely rise above a whisper; and some have drool constantly leaking from the corners of
their lips. Modern therapeutics hold the symptoms at bay for only so long.

But perhaps we, like Dr. James Parkinson, can hold out some semblance of hope. In an

article in the New York Times in February 2015, Jon Palfreman, a professor of broadcast journalism at the University of Oregon and author of the book Brain Storms, described his own experience with PD. He explains that one biotech company is now
experimenting with genetically engineered compounds from viruses to neutralize specific proteins that build up in the brain and may be implicated in PD. This is a
very interesting development and one that we ought to keep our eyes on. Clearly, we have come a long way from draining blood in
order to treat PD. But we are also far from being able even to slow it down, much less stop it.

On Evidence-Based Medicine

Physicians throw around the term “evidence-based medicine” a lot. Whether it’s an antibiotic, IV fluid, or blood-pressure pill, the decision about how to
use a drug often comes down to the question: is the treatment evidence-based? But what does that mean? Evidence-based medicine is “the conscientious, explicit, and judicious use of current best evidence in making decisions” about patient care. This definition suggests that clinicians or researchers fastidiously tested and confirmed the effectiveness of an intervention with a robust, replicable, and
accurate scientific study.

Designing a valid study, however, is difficult because there are many potential biases that can render its conclusions inaccurate. Here are some examples:

  • Selection bias occurs when subjects are assigned in a nonrandom manner to different study groups.
    If a physician runs a trial to test the efficacy of a drug he may put those who have a better prognosis in the treatment group, as opposed to the
    non-treatment group. Consequently, scientists can claim this new treatment is successful even though it was tested on those who were most likely to improve
    anyway.
     
  • Sampling bias, where subjects chosen for the study do not represent the general
    population, can mean that a study’s findings do not apply to the general population.
     
  • The Hawthorne effect arises when subjects change their behavior because they know they’re being
    watched by a researcher or physician.
     
  • Confounding bias describes a situation in which one factor can
    distort the effect of another. If a researcher studies the effects of alcohol on health but ignores the fact that many people who drink alcohol also smoke, alcohol
    will appear to have a worse effect on one’s health due to the consequences of smoking.
     

Another kind of bias has been in the news a lot recently with regard to prostate-cancer screening.
Here’s how Dr. Michael S. Cookson, a urologist at Vanderbilt University, describes this kind of bias:

Lead-time bias suggests that the natural history of the disease is not truly affected by screening. For example, a patient may be diagnosed with prostate
cancer at 50 years of age through … screening. He then undergoes treatment but ultimately progresses and dies at 60 years of age. Accordingly, the same
patient without screening develops symptomatic bony metastases [late stage cancer] at age 58, undergoes treatment with androgen deprivation therapy, and
dies at age 60. Thus, in this theoretical scenario, even though he was diagnosed 8 years prior through screening, his death was not affected by screening
or early detection.

In other words, early detection of cancer makes it seem as if your lifespan is increased simply because you know that you have cancer for a longer period
of time. But you don’t necessarily live longer because of that.

Image via Shutterstock

There are many other kinds of bias but the descriptions above give a sense of how difficult it is to design experiments without it. The most powerful
studies account for bias with a double-blindedrandomized, and controlled trial. Participants and researchers are both blind in that they do not
know who is getting the placebo treatment and who is getting the trial treatment. Participants must also be randomized to the treatment group or the
placebo group — that way, there is no selection bias and there is less confounding bias. Controlled just means that there must be a control group, which is
a group that does not receive the disease therapy or that receives the current best therapy for the disease. Researchers can then compare the effectiveness of
the newest therapy to the current best available therapy. Another way to avoid confusing results is to use crossover studies, where a patient serves as his or her own control. The patient receives the
real therapy for a given period of time and then receives the placebo for a given period of time thereby eliminating confounding bias.

A statue of Avicenna in Tajikistan
Nikita Maykov / Shutterstock.com

Interestingly, this approach to scientific studies, albeit a much less sophisticated version, dates back to the eleventh-century Islamic philosopher and
physician, Avicenna. In his Canon of Medicine, a
multivolume medical encyclopedia, Avicenna expanded upon the work of Galen, the ancient Greek physician. In her 2008 article “Islamic Pharmacology in the Middle Ages: Theories and Substances,” Danielle Jacquart explains that Avicenna endorsed
the concept of using drugs based on past results of experiments:

As for the powers only known through experiment, these were not deduced from the qualities or the appearance of pharmaceutical ingredients, but they rather acted through their whole form or substance. Their action could only be revealed
by an experimental test. Yet this did not mean that ordinary physicians themselves had to undertake such experiments. Rather, they relied upon experiments
carried out by their predecessors.

Similarly, when today’s physicians choose, say, an antibiotic for a bacterial infection, they rely upon experiments carried out
by their predecessors.

When I started medical school, I assumed that everything in medicine was evidence-based; that scientists rigorously studied and validated every treatment.
After all, we should not treat a patient with a drug unless we know it works. But it turns out that there is not always evidence to support every decision physicians make.
Perhaps a study has simply not been done or the evidence collected was equivocal or inconclusive. Or perhaps some real-life situation has arisen that is complicated in ways that could not possibly have been tested in an experiment. In these cases, physicians must base their decisions on
experience.

Let’s take the example of IV fluids, which are a basic staple of medical care, as I’ve mentioned in multiple posts. One would think that the data would be fairly
clear on which types of IV fluids are best. Unfortunately, it’s not at all evident. Some background: there are two major types of IV fluids, colloids and crystalloids. Crystalloids contain water and electrolytes that are similar to those circulating in the blood. Some examples of these are Lactated Ringer’s and Normal Saline. Colloid fluids contain water and electrolytes, too, but they also contain osmotic
substances like albumin, which draw fluid into the vascular space. Fluid in the body can be inside the blood vessels or outside the blood vessels, and
colloids keep fluids in the vessels.

Ostensibly, colloid fluids ought to work better in certain situations. For instance, when a patient has very low blood pressure, the way to increase blood
pressure is to increase fluid within the vasculature. However two studies, one in the New England Journal of Medicine in 2004, and one in the Annals of Internal Medicine in 2001, concluded that there were no
significant differences in mortality in various medical situations when using one type of fluid versus the other. So, barring significant differences in
cost, which fluids does one use in the hospital when patients need hydration or increased blood pressure?

Image via Shutterstock

Given that the evidence is unclear, we use what our mentors use. During surgery rounds, for example, I asked “why are we using Lactated Ringer’s (LR)?” A resident replied that the evidence was inconclusive and the attending used LR so he used LR. Until we have better evidence, this seems completely
legitimate even if it makes us uneasy because there’s no clear consensus. Furthermore, this demonstrates that though certain ideas may make sense in theory, they
fail when standing against the test of scientific rigor. Thus, evidence-based medicine also requires open-mindedness.

Let’s also look at an example of how evidence-based medicine changes medical practice rapidly on a day-to-day basis. This past summer, the treatment for Parkinson’s disease (PD), a disease of certain neurons in the brain, underwent a change. Previously, movement disorder neurologists
recommended dopamine agonists as a first-line treatment for the disease. The alternative is carbidopa-levodopa, a medication that is more effective at controlling PD symptoms. However,
carbidopa-levodopa causes more side effects, such as dyskinesias, or compulsive and uncontrollable
movements (some of these can be irreversible), the longer one takes the medication. And, given that patients with PD can live a long time, neurologists
wanted to put off using it so that patients would not experience these effects so soon after starting medication.

But this past June, a study in The Lancet compared starting a dopamine agonist with starting carbidopa-levodopa in patients with newly diagnosed, early PD. And the researchers found that there is not a significant difference in patient-rated mobility scores (a fancy way of saying movement difficulties as well as quality of life) when
starting with levodopa rather than dopamine agonists. I observed the direct practice changes as a result of this study. In the neurology clinic, the
attending, after reading this article, changed the way he spoke to patients with newly diagnosed PD. Instead of saying that it is better to avoid
carbidopa-levodopa first, he told patients that it was their choice what drug they wanted to start taking. This is a wonderful example of why
evidence-based medicine and research is so important and how it can affect the practice of medicine — very concretely, very directly, and very soon after the research is published.