Book extract: 'A World of Resistance' examines medicine's most powerful breakthrough

Excerpted with permission from Assa Doron and Alex Broom, authors of 'A World of Resistance: India and the Global Antibiotic Crisis', published by Harvard University Press

The quest for antibiotic autonomy: Antibiotic gold rush

The 1940s to 1960s were a frenzied period of discovery and commercialization in the pharmaceutical world. Unlike penicillin, which Fleming and his colleagues refrained from patenting, new antibiotics were developed with profit in mind.

Pharmaceutical companies and research institutions engaged in intense competition to be the first to discover, develop, and market new antibiotics. Each entity aimed to gain a competitive edge in the lucrative pharmaceutical market by patenting and producing the latest, most effective antibacterial drugs before their competitors.

The “antibiotic gold rush” saw the emergence of crucial drugs like streptomycin and aureomycin. The processes of research, development, manufacturing, commercialization, and distribution behind the new antibiotics reshaped not just medicine but also agriculture and global trade. The story of aureomycin makes clear the transformations underway in this era.

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Aureomycin was the first broad-spectrum antibiotic, meaning it was effective against both gram-positive and gram-negative bacteria. Yellapragada SubbaRow, an Indian-born scientist whose contributions were often overshadowed, was involved in its development. Born to an impoverished Brahmin family and initially trained in Ayurveda, SubbaRow managed to complete a PhD in biochemistry at Harvard in 1930. He later joined Lederle Laboratories in the United States, where he was instrumental in developing aureomycin. The drug was considered a step up from penicillin, a narrow-spectrum antibiotic with an efficacy profile limited to gram-positive bacteria.

Though SubbaRow’s contributions were largely elided in American pharmaceutical research, an obituary in the New York Times acknowledged his ground-breaking work: “His most recent major accomplishment was the completion, with his associates, of work that led to the creation of aureomycin, a new product for the treatment of infections that do not respond to penicillin or streptomycin.” The 1948 obituary hints that resistance to the once “wonder drug” penicillin was already emerging. SubbaRow’s research on aureomycin tackled the growing resistance to penicillin, highlighting the urgent need for newer and more effective antibiotics.

Aureomycin had an additional virtue: its versatility. It had far-reaching applications not only in human health but also in veterinary medicine and agriculture, particularly in what became known as nontherapeutic uses. As Maryn McKenna observes in her research on the poultry industry, aureomycin was “about to alter the entire structure of agriculture - and affect land use, labor relations, international trade, animal welfare, and the diet of most of the world.”

The transformative effects of aureomycin in agriculture call to mind another technology. Initially lauded for their revolutionary potential, pesticides were soon overused and misused. Pollution, environmental damage, decreasing biodiversity, and the rising resistance of insects to indiscriminate chemical treatment was causing alarm by the 1960s. The environmentalist Rachel Carson’s 1962 book, Silent Spring, is a well-known clarion call. In contrast, in India, M. S. Swaminathan, the architect of the Green Revolution, advocated for the use of agrochemicals to increase crop yields. His long-standing support, which was tempered over time by growing concerns about environmental sustainability, underscores the complexity of debates surrounding new agricultural technologies, where enthusiasm is frequently balanced by caution.

Increasingly, more voices were highlighting the unforeseen consequences of embracing scientific advances without ample caution. Once-effective solutions to agricultural challenges became impotent and left greater challenges in their wake. The idea of sustainability arose to highlight the short-termism of industrial agriculture.

In India, SubbaRow was celebrated as a national hero whose achievements abroad could now fuel the nation’s progress at home. The emerging nation was committed to self-sufficiency in everything from agriculture to pharmaceuticals. SubbaRow’s legacy showed that India could not only compete on the global scientific stage but potentially dominate it. In 1953, an aureomycin plant dedicated to SubbaRow’s memory was opened in Pimpri, the site of other antibiotic-manufacturing facilities. The Times of India reported, “One of India’s greatest scientists was posthumously honored on Saturday with the dedication to his memory of a pharmaceutical plant, which was described as a momentous addition to India’s weapons for fighting disease.”

The inauguration of the aureomycin plant in SubbaRow’s name was not just an industrial milestone; it was a testament to postcolonial India’s resolve to chart its own course in modern medicine. It was also a US-India collaboration. In fact, it was a Lederle Laboratories facility, celebrated by the US ambassador to India. The ambassador observed that the plant demonstrated “a significant step forward restoring to India its former pre-eminence as a source of healing drugs.” A complex dance of cooperation and competition was unfolding between India and the United States in the pharmaceutical arena. As discussed in Chapter 2, this relationship would come under intense scrutiny decades later, in debates about the quality of Indian-manufactured antibiotics exported to the United States.

For the moment, the antibiotic plants in Pimpri represented nation building through pill production. They embodied Nehru’s dream of India as a scientific powerhouse. Imagery of international dignitaries touring the aureomycin facility, including a visit by Nehru and his daughter Indira in 1956, became iconic. One enduring image shows Nehru, in his characteristic cap, wearing a lab coat and peering intently through a microscope at samples. Indira and a man who is possibly a plant scientist look on with interest. It captures an ideology of state building through modernization and scientific acumen. India’s new rulers examined the microscopic foundations of their nation’s future.

Jawaharlal Nehru and the penicillin factory, Pune, 1956. Photo credit: Wikimedia Commons

However, the image and the plant also highlight the complex relationship between the former colony and its imperial masters. Postcolonial India asserted its independence not by rejecting Western medicine but by claiming mastery over it. The antibiotics plants in Pimpri showed that India could turn the tools and technologies of the colonizer to its own advantage, as a producer and not merely a consumer of foreign pharmaceuticals.

The Downsides of Antibiotics

By the late 1950s, India’s antibiotic production was considered a great success. The parliamentary Estimates Committee report in 1961 assessed the Hindustan Antibiotics factory in Pimpri: “The Factory, though originally planned to produce 3.8 to 9 million mega units per year, is now expected to yield about 15 million mega units of penicillin per year, as a result of using better yielding strains and manufacturing methods evolved in the factory.” India’s Lower House of Parliament (Lok Sabha) praised the plant for its production capacities and ability to maintain low retail prices in comparison to world markets.

However, concerns about antibiotics, ranging from misuse and adverse reactions to dubious formulations, emerged. The Asian flu outbreak of 1957 provided clear evidence of wide indiscriminate use. Without available vaccines, antibiotics were seen as the primary defense against the flu, a silver bullet used extensively although experts warned of their ineffectiveness against viruses. Even Ayurvedic practitioners were permitted to use the popular strepto-penicillin combination. The Times of India reported, “Some doctors . . . stated that many patients who visited them insisted they should be treated with the antibiotics and kicked up a row if the doctor refused to oblige.”

The reality of runaway antibiotic use to treat viral flu highlights the key challenge that faced India’s pharmaceutical landscape in the mid-twentieth century. The task of managing public health concerns and infectious disease risks required more than the limited medical resources available. Popular knowledge about appropriate antibiotic use was sorely lacking. Public health concerns were frequently raised in the English-language media during the early years of antibiotic therapy in India. Such concerns often sparked spirited debates about the need for the regulation of indigenous medical systems.

Under British rule, Western medicine was promoted. The Raj positioned itself as the primary producer and distributor of pharmaceuticals. However, indigenous therapies remained popular. During the colonial period, the British sought to systematize and codify indigenous medical systems as part of their broader efforts to control and manage knowledge systems in India. This process involved the establishment of institutions, such as colleges, where traditional medical practices were taught in a formalized, standardized manner, often under the supervision of colonial authorities. Since the nineteenth century, these medical systems - indigenous and allopathic - “were intensely interlocked in the competition for legitimacy and, even more crucially, for government pecuniary support and patronage.”