Therapeutic evolution and the challenge of rational medicine.

n engl j med 367;12 nejm.org september 20, 2012 1077 Medical School. Warren’s clinical descriptions should still sound familiar to anyone who has treated coronary artery disease. His therapeutic strategies, in contrast, appear downright bizarre. He treated one patient, a “plethoric” clergyman, with stimulants, bloodletting (see Fig. 1), and topical ether, then with more bloodletting, opium, powerful laxatives, and caustic agents that blistered the skin over his sternum. As the patient’s anginal attacks increased in frequency and intensity, Warren tried asafetida (see Fig. 2) — a botanical resin known as “Devil’s dung” for its sulfuric, excremental smell — and additional caustics such as silver nitrate to provoke draining blisters on his thighs and arms. With the clinical picture worsening, Warren sent his patient on a therapeutic voyage to Georgia, “where he passed the winter, and suffered less violent attacks than in a more northern climate” (1812a; see box for cited Journal articles). When the minister returned to Boston and his attacks again intensified, Warren added arsenic and bled him vigorously, to no avail. Before his patient’s death, Warren noted that the minister’s condition improved somewhat with the use of tobacco. Seen at a remove of two centuries, Warren’s treatments seem excessive, even futile. Apart from opiates — which still have a role in treating severe angina — they have nothing in common with today’s cardiovascular therapeutics. Thrombolytic agents, antiplatelet drugs, beta-blockers, stents, and bypass surgery — the mechanisms of which are understood in many cases at a molecular level — have demonstrably improved the patient’s odds of surviving and leading a productive life, even after a major heart attack. Yet an examination of the history of therapeutic practice can do more than simply chart our progress over the past two centuries. It can also demonstrate how change occurs in medicine, revealing what has been gained and what opportunities have been lost along the way. As generations of physicians have sought more rational bases for medical practice, they have swung between the poles of enthusiasm and skepticism. They have sought therapeutic power 20 0TH ANNIVERSARY ARTICLE