The Laws of Medicine (7 page)

In reality, things have panned out quite differently: despite the increasing accuracy of tests, studies, and equipment, the doctors of today have to contend with priors, outliers, and biases with even deeper and more thoughtful engagement than doctors of the past. This is not a paradox. Tests and therapies
may have evolved, but so has medicine itself. In Lewis Carroll's
Through the Looking-Glass
, the Red Queen tells a bewildered Alice that the queen has to keep running to stay in place—because the world keeps running in the opposite direction. Despite the sophistication of medical technologies, uncertainties have remained endemic to medicine because the projects that medicine has taken on are vastly more complex and ambitious. Thomas imagined a future in which machines took care of sick people. Now we have better machines, but we are using them to take care of sicker people.

In Philadelphia, a six-year-old girl with a lethal, therapy-resistant, relapsed leukemia recently had her immune cells harvested, genetically modified with a virus carrying a gene that kills leukemia cells, and then reinjected into her body to act as a form of “live” chemotherapy. The cells sought out and killed her cancer with exquisite efficacy, and she remains in a profound remission. At Emory, a neurosurgeon implanted a tiny electrical stimulator into the cingulate gyrus in the brain of a woman with profound depression. Seconds after the “brain pacemaker” was pulsed on, the woman described the lifting of a permanent dark fog of despair that had been recalcitrant to the highest doses of antidepressant medicines.

The Philadelphia experiment illustrates the nature of the complexities and uncertainties faced by the new medicine. Hours after the young girl with relapsed leukemia was injected with her cancer-seeking T cells, she experienced the most potent form of inflammatory response. Her physiology sensed the macabre aberration of her “self” turning on itself—an immune
system attacking its own body (in fact, her T cells were attacking her cancer cells)—and she spiked a fever. Her blood pressure dropped. Her kidneys began to falter, her vessels began to clot and bleed at the same time, and she lapsed into a coma. A fleet of lab tests was sent out to monitor her status, and dozens returned with abnormal values. Which of these were the outliers, and which were the abnormal factors truly contributing to her terrifying inflammatory response? Her blood counts indicated that she might be in the beginnings of a remission—but was there an inherent bias in using these parameters to judge a remission in the setting of an acute inflammatory response?

Of all the abnormal lab values—every number capitalized, bolded, and flagged in violent red—one skyrocketing factor caught the eye of her physicians. Why? Because some prior knowledge indicated that the factor, called interleukin-6, or IL-6, sat at the hub of the inflammatory response. But also because there happened to be a drug against it: by pure chance, the leader of this trial happened to have a daughter who happened to have juvenile arthritis who happened to have been treated with a medication that blocked interleukin-6. Two days after the young girl's initial T-cell transfusion, doctors and nurses were pulling things off the shelves to see if any agent might work against the immune attack and consequent organ failure. “She was as sick as any human can possibly be,” one physician recalled. Her vital signs fluttered on a precipice. In a last-ditch maneuver, she was injected with the antiarthritis drug. As the doctors watched, bewildered, the fever reversed. The kidneys, lungs, blood, and the heart returned to normal function. By the
next morning, she awoke from her coma. One year later, she remains in remission, with no sign of cancer in her bone marrow.

Is the case over? Far from it. Should this girl be given chemotherapy now to “consolidate” her remission—as conventional wisdom might suggest—or would the added chemotherapy kill the very cells in her immune system that are keeping her disease in check? We don't know because there are no priors. Is her response normal, or is she an outlier? We won't know until we can build a model of the nature of her response and try to make all the available data fit it. How will we objectively judge this therapy in a clinical trial when no other comparable therapies for relapsed, refractory leukemia exist? Can such a trial ever be randomized?

This experiment—and hundreds of similar studies at the frontiers of medicine—suggest that human decision making, and, particularly, decision making in the face of uncertain, inaccurate, and imperfect information, remains absolutely vital to the life of medicine. There is no way around it. “The [political] revolution will not be tweeted,” wrote Malcolm Gladwell. Well, the medical revolution will not be algorithmized.

....

One last thought: there is no reason to believe that there are only three laws of medicine. My own laws are personal. They stood by me throughout my internship, residency, and fellowship. They saved me from the most egregious errors of judgment; they helped me diagnose and treat the most difficult of the cases that I encountered in my practice. Every year, I begin my teaching rounds at the hospital by explaining my version of the laws to the new medical residents. Each time I see a new patient in the wards or in the clinic, I remind myself of them.

Yet if there are other laws, I suspect that they will also concern the nature of information and uncertainty at their very core. “Doctors,” Voltaire wrote, “are men who prescribe medicines of which they know little, to cure diseases of which they know less, in human beings of whom they know nothing.” The pivotal word in this scathing description is
know
. The discipline of medicine concerns the manipulation of knowledge under uncertainty. Abstract away the smell of rubbing alcohol and bleach; forget the adjustable beds and ward signs and the gleaming granite of hospital lobbies; erase, for a moment, the many corporeal indignities of a man in a blue cotton gown in a room or the doctor trying to heal him—and you have a discipline that is still learning to reconcile pure knowledge with real knowledge. The “youngest science” is also the most human science. It might well be the most beautiful and fragile thing that we do.

....

I'd like to thank Michelle Quint for her careful editing of the manuscript and her remarkable equanimity in guiding this book to its final form. June Cohen and Chris Anderson helped shape a very shapeless idea of “laws” into this book. I owe a special debt to Sarah Sze, Nell Breyer, Sujoy Bhattacharyya, Suman Shirokar, Gerald Fischbach, Brittany Rush, and Ashok Rai for their comments and criticisms and to Bill Helman for helping me understand some of the most important ideas about uncertainty and the future of technology.

PHOTO: BRET HARTMAN/TED

Siddhartha Mukherjee
is a cancer physician and researcher. He is the author of
The Laws of Medicine
and
The Emperor of All Maladies: A Biography of Cancer
, winner of the 2011 Pulitzer Prize in general nonfiction. Mukherjee is an assistant professor of medicine at Columbia University and a staff cancer physician at Columbia University Medical Center. A Rhodes scholar, he graduated from Stanford University, University of Oxford, and Harvard Medical School. He has published articles in
Nature
,
Cell
,
The New England Journal of Medicine
, and
The New York Times
. In 2015, Mukherjee collaborated with Ken Burns on a six-hour, three-part PBS documentary on the history and future of cancer. Mukherjee's scientific work concerns cancer and stem cells, and his laboratory is known for the discovery of novel aspects of stem cell biology, including the isolation of stem cells that form bone and cartilage. He lives in New York with his wife and two daughters.

Read the book and watch the talk.

Siddhartha Mukherjee's TED Talk, available online:

www.TED.com

Meet the authors, watch videos and more at:

SimonandSchuster.com

authors.simonandschuster.com/Siddhartha-Mukherjee

Siddhartha Mukherjee's TED Talk, available for free at
TED.com
, is the companion to
The Laws of Medicine
.

PHOTO: Bret Hartman/TED

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