Pharmageddon. David Healy

      Medical concerns about these proprietary medicines led to calls for their regulation. This resulted in the establishment in the United States in 1906 of the Chemical Bureau, the first regulator of medicines, the forerunner of the Food and Drug Administration (FDA), established in 1938, and all such regulators since.¹⁹ The Chemical Bureau was set up to force companies marketing medicines to specify on the label what the product contained. This minimal intrusion into the market ironically initiated a process whereby increasing regulation forced smaller companies unable to meet the demands of regulation out of the market and the consequent growth of the surviving corporations, with ever greater marketing capabilities, that have a century later brought us to the brink of Pharmageddon.

      Having fought for over 150 years against quackery first and alternate or complementary medicines latterly, it has become part of the medical profession's self-image that it has nothing to do with the kind of marketing that makes extravagant claims for spurious remedies. Buyers might have to beware in other domains of life but not when it comes to medical care.

      This confident self-belief can still be found in most everyone involved in healthcare, from doctors and administrators to nurses, and it is taken at face value by a wider public. The idea that most doctors have been body-snatched and replaced by someone working for a faceless marketing department seems at first inconceivable to most people, the germ perhaps of an amusing idea for a television series, but nothing more.

      Doctors, and many of the rest of us, think we see the marketing in medicine—some free pens and lunches, plenty of free samples, perhaps golfing trips for some select doctors to the Caribbean—and feel able to discount this. Modern safeguards are supposed to be in place to manage anything a marketing department dreams up. Our drugs have to pass the scrutiny of regulators and they can only do this if there are controlled trials to show that they work. After that they are available by prescription only from doctors who are increasingly constrained in what they can do by guidelines drawn up by experts on the basis of these treatment trials. These guidelines are built into standards of care across all areas of medicine, and doctors straying from these standards in response to some marketing gimmick risk being sued or losing their medical license.

      With these safeguards in place, the idea that medicine could be sucked into a machine that has as little interest in the health of the people who consume its products as a shoe company has in their fitness but that has a lot of interest in using disease and ill health to distinguish drugs that are often as indistinguishable in their effects as one brand of bottled water is from another will be met with incredulity or incomprehension in many quarters. It doesn't make sense that seriously ill people would pay more heed to the color of the pill or its brand name than to the question of whether the treatment they are on is likely to do more good than harm. Marketing, after all, has little impact in states of famine. Starving people don't hold out for paninis or rye bread.

      But this is to miss the point. In the current setup, it is the doctor not the patient who consumes, and the doctor is rarely in extremis. What doctors dispense will have a branded glow to it. They will be giving it for a condition as likely as not that they were never taught about in medical school, a condition, in fact, now being marketed by some company. Neither the doctor nor the patients who receive a treatment, nor those who draw up the treatment guidelines, are likely to find out that this treatment may actually be less effective than older treatments recently retired medical colleagues might have prescribed. The doctor is also unlikely to be aware that the markup on drugs like Lipitor, Prozac, and Nexium may be up to 2500 percent. In 1912, medical associations inspired major changes by questioning a markup of 500 percent on proprietary medicines of the day. In 2012 there is close to silence on markups of 2500 percent. This silence is linked closely to the failure by medical practitioners to understand how industry now brands its products.

       THE ONCE AND FUTURE BRANDS

      Philippe Pinel working in Paris in 1809 had few effective treatments aside from some herbs and metals, along with remedies drawn from opium for pain relief or sedation, willow bark also for pain, fever bark for malaria, and foxglove for heart failure. A few years later, in the 1820s, advances in chemistry made it possible to extract opiates from opium, quinine from fever bark, and digitalis from foxglove, so that standard doses of treatments could be given. Then in 1860, just as Oliver Wendell Holmes was consigning almost all available drugs to the bottom of the sea, a new set of medicines emerged, giving doctors like Worcester and Cabot by the 1890s new therapies to employ and the hope of more to come.

      In the second half of the nineteenth century, a series of mostly German chemical companies, such as Bayer, BASF, and Hoechst grew rapidly because of the newfound ability to synthesize dyes from coal tars. These dyes transformed our wardrobes from a series of drab brown and green outfits to yield the blues and pinks and yellows we now have. They also allowed human tissues and cells to be distinguished, giving rise to histology, and bacteria to be stained, creating bacteriology. The ability to distinguish among bacteria made it possible for doctors to differentiate between diphtheria, the most common cause of childhood mortality, and other throat infections, for instance. Doctors like Worcester had been called repeatedly to homes to try to save the lives of children being literally garroted by membranes from the diphtherium bacteria forming deeper and deeper down in their windpipe. They would cut open the child's throat and pass in a tube and hope no membranes formed even lower down, though all too often this failed. Distinguishing diphtheria from other bacteria led to the synthesis of diphtheria antitoxin in 1894. As the membranes from the illness faded in response to an injection of the antitoxin, so also the nightmare of diphtheria began to fade away in areas where the antitoxin was available.²⁰ Successes like this heralded a future of pharmaceutical magic bullets.

      Discovering a new dye or drug in Germany of the late nineteenth century did not give a company sole rights to that product. If another company could demonstrate that it was able to produce the compound by a different process than that specified by the original company, the second company was entitled to manufacture its version of summer blue, say, or acetylsalicylic acid. When acetanilide, one of the drugs derived from dyes, was shown to be antipyretic (fever reducing), for example, well over ten companies found different ways to produce it. No company could easily make a blockbuster drug in these circumstances. Faced with this scenario, in 1886, another German company, Kalle, borrowing a practice from the proprietary industry, trademarked the name of their version of acetanilide—Antefebrin. Sales boomed. Other companies took note, and Bayer followed by registering Aspirin and Heroin in 1898, names with far more resonance to this day than acetylsalicylic acid or diacetylmorphine. The basis for both of these painkillers had first been created close to fifty years earlier, so Aspirin and Heroin were new social rather than pharmaceutical creations.²¹

      The first brands had got a foothold within medicine, and the medical profession began to make an uneasy accommodation to this changed reality. Medical students were taught to refer to the generic names of drugs—diacetylmorphine rather than Heroin. For almost a century this denial of brands worked passably well, but to continue to pretend that doctors today typically still prescribe generic drugs rather than brands passes beyond denial into fantasy.

      This denial was helped by the fact that the focus in promoting the new magic bullets from diphtheria antitoxin to Heroin was directed toward doctors rather than the public at large, and toward conquering the scourge of disease rather than capitalizing on the discontents of everyday life. Sales of these new compounds were promoted by visits from company representatives to doctors and ads in medical journals, rather than the hoopla customary to the proprietary medicines' industry. There was minimal effort to subvert medical judgment, in part perhaps because until the 1940s there was relatively little to sell.

      Then, in 1937, prontosil red, a dye produced by the pharmaceutical conglomerate IG Farben, gave rise to the sulfa antibiotics, which had as great an impact on lethal conditions like bacterial endocarditis, an infection of the lining of the heart, as diphtheria antitoxin had on diphtheria forty years earlier. Other antibiotics followed in the 1940s and from the sulfa nucleus came a host of other drugs, including diuretics to remove excess body fluid in heart failure, antihypertensives to lower blood pressure, and oral hypoglycemics to lower blood sugars. In the 1950s, dyes such as methylene blue and summer blue led to the antipsychotics and antidepressants.