Über coca: Sigmund Freud, Carl Koller, and cocaine.

IN THE SPRING OF 1884, A 28-YEAR-OLD VIENNESE NEUrologist named Sigmund Freud published “Uber Coca,” a superb medical analysis of cocaine hydrochloride. Although the monograph was an early career milestone for the ambitious physician, it also represented a missed opportunity. Using himself as his experimental subject over several months, Freud consumed a great deal of cocaine as he recorded the drug’s physiological effects and potential therapeutic uses. However, he skimmed over cocaine’s most important clinical use as a local anesthetic. In a hurried last paragraph, a postscript really, Freud noted that “cocaine and its salts have a marked anesthetizing effect when brought into contact with the skin and mucous membrane in concentrated solution.” Without offering any additional data or experiments, Freud merely concluded that these properties “should make it suitable for a good many applications.” The person who did capitalize on describing cocaine’s anesthetic properties was Freud’s colleague Carl Koller, an aspirant (intern) in ophthalmology at the Vienna Allgemeines Krankenhaus (General Hospital). That Koller became so interested in local anesthesia was a direct result of the operation he frequently performed: cataract removal. Although practiced since antiquity, it remained a dreaded procedure in 1884. After all, without pharmaceutical assistance, cataract removal was not only excruciating, it required a patient to watch as the surgeon, literally, poked him or her in the eye. Few have re-created the operation’s awful immediacy as well as the British novelist Thomas Hardy: “It was a like a red-hot needle in yer eye while he was doing it. But he wasn’t long about it. Oh No. If he had been long I couldn’t ha’ beared it. He wasn’t a minute more than three quarters of an hour at the outside.” With the advent of ether and chloroform in the mid19th century came great hopes among ophthalmologists for making cataract removal less traumatic. But these anesthetic agents often induced vomiting in patients—which in turn created alarmingly high pressures in the abdomen, chest, and head that are not conducive to performing delicate eye surgery. During the summer of 1884, Koller slaved over a formal address on cocaine for the international Ophthalmological Congress to be held that September at Heidelberg. Too poor to afford the travel expenses to Germany, he asked Josef Brettauer, a 49-year-old ophthalmologist, to read his paper at the meeting—a common practice in an era when travel was both costly and arduous. The presentation was nothing short of spectacular. As the world’s most distinguished eye surgeons took their seats in the auditorium, Brettauer approached the podium. After explaining what Koller had been working on for the past few months, Koller’s surrogate snapped his fingers and called for a diener to wheel in a gurney bearing a large dog. With a theatrical flair, the physician showed the audience that the animal was alert, comfortably seated on a cushion, and loosely tied down on the gurney. He then took a calibrated dropper full of cocaine solution, delicately held the canine’s left eye open with his thumb and forefinger, and introduced 3 or 4 drops of the elixir. Brettauer let 1, then 2, minutes pass in silence—a period that seems like a lifetime when giving a lecture before a crowded room. Satisfied that the cocaine had taken effect, he thrust a forceps toward the dog’s eye. While the animal’s right eye blinked in response to this threat, the left eye remained still. Brettauer deftly touched the canine’s left eye with the surgical instrument and the results were astonishing: nothing happened! No whimpering, no barking, not even a flinch—that is, until the crowd sighed in relief that no harm had come to the dog and burst into uproarious applause. The development of a topical agent that could safely render a patient insensate to the surgeon’s pointedly sharp manipulations while completely awake was earthshaking. It was front-page news that captured the attention of just about every physician (and dentist) in the world. It also enabled pharmaceutical companies to make a fortune marketing cocaine and, later, safer local anesthetics like procaine hydrochloride (Novocain) and lidocaine hydrochloride (Xylocaine). Freud, understandably, was less than thrilled about Koller’s achievement. Working in the same hospital, where gossip of successes and failures traveled quickly, could not have been an easy cross for the young, sensitive physician to bear.