Pharmageddon. David Healy

new drugs all came branded by their manufacturers. These were brand names that spoke of medical diseases and or chemical contents rather than the old style panaceas whose promises were in inverse proportion to their efficacy. Thus just as Kalle had given doctors Antefebrin (antifever), Merck in the 1960s gave them Diuril (for diuresis), and Tryptizol (amitriptyline) as an antidepressant. Initially, as with brands such as Hoover and Mercedes, these new brands traded on quality. The brand stood for the fact that the drug was produced by a reputable company that was linked to previous breakthroughs and doctors could accordingly be confident about the pedigree of the product. This was an era of “magic bullets”—penicillin, the thiazide antihypertensives, and antipsychotics such as chlorpromazine—which would have marketed themselves, branded or not.

      Indeed, by the 1960s it seemed to many doctors as if medicine had faced down the destructive forces of marketing as the proprietary medicines industry withered away with the advent of these new magic bullets. Few drug company invaders in the 1950s and 1960s in dead of night appeared to crawl out of the Trojan horse that brands had introduced to the medical citadel. But the fatal breach had been effected. Changes to the patent laws in the 1960s, allied to the fact that these new drugs were available by prescription only, laid the basis for the emergence of blockbuster branding in the 1980s.

       PATENT MEDICINES

      Patents offer an exclusive right to produce a good or service. They are granted by a state, are even older than brands, and once provoked almost as much hostility within medicine as brands. Patenting drugs, and thereby restricting access to them either physically or by virtue of the increased price that comes with a monopoly, was for centuries regarded as incompatible with a vocation to alleviate disease. In the case of modern drugs, this period of monopoly lasts for twenty years.

      The first patent law was enacted in Venice 1474, and the idea then spread rapidly throughout Europe.²² In Britain, after widespread complaints about abusive patent monopolies being granted by the Crown for long-existing technologies, the law was tightened in 1624 to limit grants of monopolies to “the sole working or making of any manner of new manufactures within this realm, to the true and first inventor and inventors of such manufactures.”²³

      Being the exclusive patent holder of a good or service meant that you could produce it at a higher price than was possible in a competitive market. This, it was hoped, might lure innovative producers to Britain, and their activities would in turn stimulate commerce and improve national revenues.²⁴ However, in return for this benefit the producer had to show plans to create something novel that plausibly brought some benefit to the wider community.

      In Britain, patents went hand in hand with the enclosure of common lands in the sixteenth century, and critics of patenting since have referred to the anticommons effect of the practice. Because science hinges on common access to all data, many scientists and free market advocates have been hostile to patenting. But the deepest hostility to patents throughout the nineteenth and twentieth centuries came from within medicine. Neither the doctors who treated patients nor the pharmacists who dispensed remedies a doctor ordered regarded the remedies they gave as industrial or commercial products or their own activities as either industrial or commercial.

      In France, the Revolution led to promulgation of a new law in 1791 that permitted drugs to be patented.²⁵ Chemists and trade associations on the one hand argued at the time for the rights of inventors to be recognized. But French physicians and pharmacists argued against patents; their vocation, they said, was to treat the sick, not to make a profit. Furthermore, patents, they predicted, would lead to an increase in the price of medicines, which would be detrimental to public health.²⁶ In 1844, the French National Assembly reversed the 1791 law and removed medicines from the domain of patentable products.

      German law did not permit drugs to be patented, but it did allow companies to defend their product by taking out a patent on the process used to make the compound. Another company could get around the monopoly that these patents created, if they could find another way to make a compound. In some cases, as with acetanilide, this was easy, and it was this that led Kalle and Bayer to trademark their new compounds, which gave them exclusive use of the brand name they chose for their product.

      American law, in contrast, allowed patents to be taken out on drugs, even though some of the fathers of the Republic were hostile to patents. Benjamin Franklin refused to take out a patent on a stove he invented while Jefferson, referring scornfully to England's willingness to let anything be patented, refused to patent a hemp-brake he invented, stating that “nations which refused monopolies of invention are as fruitful as England in new and useful devices.” In this spirit, the nation's patent office was initially stringent in its review of applications for drug patents. In 1922, for example, Lilly attempted but failed to get around the patent on the production of insulin held in the public interest by the University of Toronto.²⁷ When in the following year, Harry Steenbock discovered that ultraviolet light activated vitamin D and sought to patent this use, he found himself accused of attempting to patent the sun and the application was thrown out. Referring back to this case in the 1950s, Jonas Salk exemplified the attitude of many American doctors at the time when he refused to patent the polio vaccine.²⁸

      The issue of patents came to a head in Britain during World War II, when Ernst Chain and Howard Florey at Oxford University demonstrated penicillin's efficacy for bacterial infections and came up with a method to produce it. Chain suggested patenting the method but Florey and the rest of the group, along with the Medical Research Council that funded the research, were opposed to patenting something so important for clinical care. This was later seen by many as a lost national opportunity, and a new law was passed in 1949 that permitted patenting of medical products.

      After the war, the position of an American or British company with a patented product was more secure than a German company with a process patent, but still these patents only applied to a national territory and so the monopoly they offered was limited. For example in the case of amitriptyline, the best-selling antidepressant during the 1960s, Merck held a patent on it in the United States, Roche (in fact the first to make the drug) held one in Switzerland, and Lundbeck in Denmark, as did a laboratory in Czechoslovakia.²⁹ Given the possibility that others might be able to make the very same product, no company could plan to market the drug profitably throughout the developed world. As a result, while some compounds that came to market during the 1950s and 1960s did extremely well, it didn't make sense for companies to invest huge effort in any one compound; except within the United States and Britain, there was no protection against another company making the same drug and cutting into profits.

      The important patent changes in international drug markets came in 1960 when France, the country that had been most opposed to patenting medicines, switched to product patents, followed in 1967 by Germany, the country that had developed more pharmaceuticals than all other countries combined. Once companies knew that applying for product patents in all major countries simultaneously blocked the development of any competing products, the way was cleared for the development of blockbusters. The possibility of truly global blockbusters came in the 1980s with the creation of the World Trade Organization's Trade Related Aspects of Intellectual Property Rights (TRIPS), which extended patent protection worldwide.³⁰ If the patent is valid, this gives a company the possibility of a monopoly on a new product worldwide for twenty years from the date of filing. From that point onward, there could only be one Lipitor, one Nexium, one Prozac, and the way was open for a company to maximize the possibilities inherent in branding—and to go as global as Coca Cola.³¹

      Compared with the vigorous debates in France that led in 1844 to a rollback in patenting medicines and the discussion of the moves that blocked the patenting of penicillin in Britain and polio vaccine in the United States, there was virtual silence in the face of these more recent changes. No one argued that patenting and commerce were incompatible with progress in science and the principles of medicine, as they had earlier.

      Several historical factors probably contributed to the silence. World War II had seen heavy state investment in medical research. This investment created partnerships between scientists, universities, and pharmaceutical companies that capitalized knowledge and contributed to the development of what is now termed