Skepticism, Seaweed, and Science

Amol Verma is a resident in Internal Medicine at the University of Toronto. His Master’s research as a Rhodes Scholar at Oxford University examined the impact of conflict on delivering health services. He developed a broad range of interests in health policy through projects such as interning with the Ministry of Health in Ontario and helping found LEAD, a program to encourage leadership development in medical education.

 

I spent my days in medical school memorizing facts.

The ‘two-hit hypothesis’ states that cancer is the result of cumulative genetic damage; lumpectomy plus radiation is equal to radical mastectomy for treating breast cancer; anti-dopamine medications suppress psychosis; the risks of hormone replacement therapy in post-menopausal women outweigh the benefits; vaccination induces adaptive immunity to protect against infectious diseases.

One fact at a time, I laid the foundation of my medical understanding. I didn’t have the time or inclination to marvel at the generations of scientific endeavor underpinning each tidbit. Or to wonder just how sturdy is the house of medicine we inhabit.

I was too busy learning answers to multiple-choice questions.

Siddhartha Mukherjee’s Pulitzer-winning history of cancer, The Emperor of all Maladies, is a poignant reminder that there is a compelling story behind every medical discovery and disaster. Often, it is only in retrospect that we can even tell the difference between the two.

In the 1890s, at Johns Hopkins Hospital, William Halsted was a renowned surgeon seeking to conquer breast cancer. Not satisfied by removing tumors themselves, he imagined a network of malignant roots affecting the surrounding healthy tissue. With fierce precision he cut deeper and deeper into his patients’ chests, stripping away not only the affected breast but also all of the muscle underneath, excavating into the armpit and through the collar bone; ‘cleaning out’ their necks.  Referring to the original Latin word for ‘root’, he dubbed this procedure a ‘radical mastectomy’.

Lacking the muscles of their chest wall, patients were left sunken, swollen, and debilitated. These were heady days as the surgical profession blossomed with new techniques and Halsted received great praise. Over the next 100 years, surgeons would continue to espouse the heroic benefits of their mammoth radical procedures, but the weight of evidence began to shift. It became clear that much smaller surgery, when coupled with radiation, produced similar results in longevity with only a fraction of the disfigurement and disability. Radical mastectomies are almost never performed today.

Radical surgery wasn’t only for cancer. In 1935 in Lisbon, a highly acclaimed neurologist, Antonio Egas Moniz, became fascinated by psychiatric disorders. He hypothesized that all variety of ailments, including depression, schizophrenia, and anxiety, were caused by the formation of fixed connections in the brain. Much like Halsted trimming malignant roots, Moniz designed a procedure to sever these connections. He began by boring holes into the patient’s head, and then swept a wire loop through their brain tissue, supposedly untethering a mat of pathological connections. He called this a ‘leucotomy’, but we know it by another name: the frontal lobotomy.

After treating just 20 patients, Moniz trumpeted his success, reporting that 35% improved greatly, 35% improved somewhat, and in 30% there was no change. We now know his procedure scarred the brains of his patients, leaving them sedate, apathetic, irrational, and sometimes disinhibited. Five to ten percent were left with recurrent seizures. The words ‘frontal lobotomy’ now conjure tragic images of Rose Kennedy or One Flew Over the Cuckoo’s Nest. But in 1949, Moniz was awarded the Nobel Prize for pioneering the field of psychosurgery, and tens of thousands of patients were lobotomized.

Medical history is rich with such stories: sincere practitioners, acting on faulty theories, causing irreparable harm in the name of healing. The purpose of recounting them here is not to find fault with physicians of old. It is to remember that such pitfalls are not just the providence of our medical past.

Using sex hormones to treat the undesirable symptoms of menopause gained popularity in the late 1960s, spurred on by the book Feminine Forever (written by the not-so-feminine Robert Wilson).  By the mid 1990s, hormone replacement therapy was recommended by the American College of Physicians, the American Heart Association, and the American College of Obstetrics and Gynecologists.  In 2001, 15 million American women filled prescriptions for hormones, making it the second most widely prescribed medication in North America. The very next year, the Women’s Health Initiative study showed that HRT actually caused an increased risk of heart disease, stroke, blood clots, and breast cancer. Weighing the risks and benefits of HRT is controversial today and it is prescribed much more rarely.

Policymakers and medical practitioners alike cannot help but act on imperfect information. Mistakes are inevitable. To learn from history is to recognize that we can reduce the gravity of our errors, and increase the likelihood of success, by avoiding the arrogance that comes with progress.

Mukherjee’s book poignantly articulates the paradox of medicine: it is both quicksilver and leaden. Rapid scientific discovery is coupled with clinical inertia.

Only thirty years ago, we did not understand the basic nature of cancer. Yet, ten years ago, I sat in undergraduate classrooms learning about oncogenes, inheritability, and carcinogens. Advancements in understanding have brought revolutions in therapy. Patients diagnosed with chronic myelogenous leukemia (CML) used to have three to six years to live. In 1998, the drug Imatinib was released. It specifically targets the protein that causes CML and increases the average lifespan for patients to 30 years. They are now more likely to die with the disease than because of it.

Yet, it still takes an average of 10 years for new scientific evidence to make its way into leading medical textbooks.  It took decades for radical mastectomies to be replaced by less invasive procedures.

It is a good thing that medical science is usually a steady ship. Overturning accepted practice should require weighty evidence, because for every paradigm-altering discovery there are a thousand failed ideas.  Yet that skepticism must not be based on an overly confident belief in the truth of our current understanding. History has shown us that great scientists marry their skepticism with intellectual humility, it’s what leaves them open to new (or old) ideas.

In the 1790s, Edward Jenner was presented with an absurd observation: that milkmaids didn’t get smallpox. In fact, this had been documented by at least six people in Germany and England over the prior 20 years but was dismissed as folklore by the wider medical community. A full century before we understood that microscopic organisms were the cause of infectious diseases, there seemed to be no reasonable explanation for this. Jenner theorized that the pus in cowpox blisters could protect against smallpox, a much more deadly disease. So he transferred the pus from popped blisters to a piece of wood and rubbed it on his patients’ arms. The pus caused a fever but no serious illness, and inoculated patients became resistant to infection by smallpox.  Thus, the era of vaccination began.

We are increasingly reliant on science – to tackle climate change, financial crises, and cancer. Reading The Emperor of All Maladies has reminded me to temper my scientific skepticism with humility; to keep open windows in my fortress of facts.

Of the many dogmas I recite daily, some will certainly be proved false in the years to come. Genetics, immunology, neuroscience – we stand only at the edge of their vast frontiers. So when I next hear about the healing powers of a diet based on green vegetables, seaweed, sulfur, and organ meats, I will try and be less quick to roll my eyes.

After all, what do I really know about seaweed?

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