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A Dearth of Curiosity

David L. Graham, MD

29 Oct 2012 11:03 PM

“Everything worth discovering has been discovered.”—Phileas Fogg, Around the World in 80 Days

“...when you have eliminated the impossible, whatever remains, however improbable, must be the truth?”—Sherlock Holmes

Each of us has been faced with times when a patient related symptoms or problems to us that just did not seem to fit. We may check references about drugs or syndromes to remind ourselves of those things we want to remember better. If we don’t find the connection there we may start perusing the literature. What do we do if we don’t find the connection published anywhere? The most common reaction is likely to discount it from that point on. If that patient brings it up again, we likely gloss over it. The things cannot be connected or it would have been published, right?

Let me tell you a story. I know of a person who as a vascular anomaly that has led to him getting a number of contrast enhanced MRIs. After the scans they would inevitably feel lousy a week or two later. After one of these scans, when they felt particularly symptomatic, this person was found to have a significant hyponatremia. Their renal function was measurably normal going into the scan. Physicians involved looked into it and reassured this person that gadolinium had not been clinically associated with hyponatremia. That assessment was accepted. Why shouldn’t it be? No other etiology for the hyponatremia was found, however.

Time came when another contrast enhanced MRI was requested. The person informed the requesting physician about the past episode and was told no connection existed. Two weeks after the scan, the same symptoms recurred and the person was found to have a significant hyponatremia again. The connection between the two was once again discounted.

The physicians didn’t entirely know whom they were dealing with, however. The person was a PhD protein biochemist who found basic science literature describing the use of Gadolinium as an agent to poison sodium channel blockers. Even faced with this science, treating physicians refuse to connect the two items to this day.

This person also showed signs of Gadolinium toxicity. This was in the face of normal renal function. Treating physicians told the person that they would have excreted the agent by that point. The scientist, however, didn’t accept that on faith. A 24-hour urine-heavy metal analysis was requested through a separate Clinical Laboratory Improvement Amendments (CLIA)-certified lab by the scientist and showed levels of Gadolinium 10 to 20 times normal.

At what point in this course would many physicians have simply assessed this person as a “quack” or even, in less gentle terms, a pain in the xxx? At what point do we lose a sense of curiosity for the unknown that would let us be willing or even want to look into this further?

There is no doubt that many of the things we hear that don’t seem to be connected really are not connected. More often than not we can make the connection to something else going on with the patient. If we cannot, we owe it to our patients not to discount their description. I know I have responded differently when faced with that dilemma after hearing this story. I now have no qualms telling a patient that I may not know of a connection and cannot find one published anywhere but I accept what they have told me. Isn’t that what they deserve?

Who knows...maybe I can be the person who describes a previously unrecognized toxicity or syndrome. After all, I refuse to accept Phileas Fogg as being correct.
Posted in: Interests


Number of Comments: 2
Stephen Strum

Thursday, January 03, 2013 11:32 AM

This may be a reflection of my age and a change in heart and mind of those younger physicians, perhaps such as yourself, but in my world of medicine the patient is always "right".   After reading your account above and recalling similar first-hand experiences many times, it is a sad commentary to the medical professional who discounts what a patient says, just because what exists in that physician's cerebral cortex cannot come up with an explanation.  As an international consultant in the sphere of prostate cancer, I would say that many physicians have no clue about how to do a literature search or to use the wonderful computer-based tools currently available.  I would also openly state that in today's world of medicine there is relatively far more focus on physician income, than patient outcome. The oldest profession has become the oldest profession for many Docs out there.  In respect to the title of your commentary, what makes a great MD (medical detective) mandates an over-expression of the curiosity gene, coupled with a sincerity in the belief and expressed in behavior as per a quote too often forgotten, or never learned:  "One of the essential qualities of the clinician is interest in humanity, for the secret of the care of the patient is in caring for the patient." -Sir Francis Weld Peabody to Harvard med students in 1917   Stephen B. Strum, MD, FACP Ashland, OR
Anthony Provenzano

Saturday, June 15, 2013 8:44 AM

David, here is an article i wrote for Joe Simone in Oncology Times. See the highlighted area. Maybe you should formulate a list of the "Graham Problems" as a challenge to the entire scientific community. Futhermore, Mayor Bloomberg's PhD incubator, Cornell Tech, on Roosevelt Island is just the kind of institution that will stimulate the kind of curiosity you talk about in your article: Oncology-Times January 25, 2009 - Volume 31 - Issue 2

The Clinical Trials in Trouble column underscores how the inertia that is inherent in the system blunts the wide-eyed curiosity that drove us into medicine in the first place. Dr. Simone correctly points out that conflating Phase I and Phase II trials into a Learn phase is one way to expedite the process. The scientific question process adopted by cardiologists is another partial solution.Identifying the most important research questions first then leads to the next set of questions: How do we most effectively decide if an intervention is worthwhile in the clinic? Recently I had the opportunity to act as matchmaker in bringing together a physicist, Dr. Lou Massa of Hunter College, who applies quantum chemistry to help solve questions regarding the quantum energies of large molecules such as insulin, with an expert in targeted therapy, Dr. Will Pao of Memorial Sloan-Kettering Cancer Center. They are exploring a collaboration to determine if Dr. Massa's work can help to screen thousands of potential targeted therapies before they are developed to see if they match quantum energies with the putative target.I believe such cross collaboration of many disciplines is the future of medical research. It attracts other thought leaders from different arenas and stimulates a dialogue that energizes the clinical trial process with new ideas. This is already being done with nanotechnology in cancer therapeutics. I also have discussed with some of my older classmates from the Cornell School of Electrical Engineering about collaborating with the newly created biomedical engineering program there. This would allow us to implement some mathematical modeling techniques that could give us a new perspective in approaching issues such as: (1) cancer screening based upon the sum of the known individual biologic models that already exist; and (2) developing models for metastases, angiogenesis, and other processes. This only scratches the surface.And let us not forget the impact of cancer research on public health issues. I believe that whatever scarce resources exist for clinical trials, that we need to be responsible in trying to assess the potential aggregate benefit to society (i.e., do we need to spend another billion dollars to develop another targeted therapy with marginal benefit as defined by measurement of surrogate end points?).

Hilbert's problems were a list of 23 problems in mathematics put forth by German mathematician David Hilbert at the Paris conference of the International Congress of Mathematicians in 1901. I believe we should create a set of the most pressing unanswered questions in oncology as did Hilbert that are prioritized by not only our colleagues but also by our non-medical collaborators.We have the intellectual capital to do great things but the regulatory inertia of the current clinical trials process in oncology is about to suffocate the potential for new and profound breakthroughs that will benefit our patients. In James Gleick's biography of Richard Feynman, Genius, he talks about how the Nobel laureate from my alma mater, Cornell, figured out how the space shuttle blew up because he did his thinking in the orthogonal plane. We need to do the same.

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