This book exhaustively covers the range of antibacterial breakthroughs that revolutionised medical care, and in doing so, the author clears the myths that have grown around the events, and paints a more realistic and non-fawning portrait of the history. The book highlights the now iconic pioneers of the antibiotic story, but the author also strove to make the point that the discoveries were collective and collaborative efforts carried out over long periods of time. As much as the narrative portrayed the sterling research work and exceptional scientific attainments that led to the discovery of the various antibiotics, it also depicts the entirely human foibles and failings that followed in their wake. The contents of the book, concise and reflective, demonstrate why the discovery of antibiotics is one of the defining breakthroughs of modern medicine.
Author: William Rosen
The discovery of antimicrobial agents was a monumental epoch in the history of medicine because it revolutionised the management of infectious diseases. This book chronicles the ‘centuries in gestation‘ of ‘the origin story of antibiotics’, recounting the breakthroughs which culminated in what it referred to as ‘a new order of battle’ in the ‘eons-long war between humanity and infectious disease’. And as he charts how antibiotics ‘professionalized healthcare in a way like nothing before or since’, the author also reviews a wide variety of microbiological concepts – from the mode of action of the antibiotics and the constituents of bacterial cell walls, to the use of antibiotics in animal feed and the emergence of antibiotic resistance. Just as the book explores the remarkable feats that transformed a predominantly prognostic practice into a rapidly curative one, it also provides incisive analyses and critical commentaries on the major landmarks and pioneers of the field. The book is also a powerful critique of the influence of pharmaceutical companies on the practice of medicine – an enduring and frequently malign feature of modern healthcare (pages 2-3, 72, 94, 234-237, 255-293 and 300-305).
Nothing conveys the impact of antibiotics on healthcare as vividly as the grim portrait the book paints of the devastation infectious diseases unleashed in the pre-antibiotic era. For example, the author cited pneumonia as the ‘second leading cause of death in the United States’ before the advent of antimicrobials, with tuberculosis being ‘the sixth deadliest killer’. A further demonstration of the effect of antibiotics on clinical practice was the author’s inspired counterfactual narrative which suggested that both George Washington, the first American president, and Napoleon Bonaparte, the French emperor, would have lived longer had antibiotics been discovered at the time of their deaths. The book also depicted the limited range of pre-antibiotic era treatments of infectious diseases, illustrating this with the example of mercury, an element that was introduced into medical practice by Paracelsus in the sixteenth century, which it said was used ‘for virtually every medical condition’. A related theme the book covered is the role played by antibiotics in establishing the dominance of the germ theory of disease over the erroneous Hippocratic ‘humoral doctrine‘, a hypothesis that he said had ‘dominated Western medicine for nearly two thousand years’. In this narrative, the book highlighted the early insights into contagion of Girolamo Fracastoro; the research of Louis Pasteur in confirming the organic nature of fermentation; the identification of the agents of anthrax and tuberculosis by Robert Koch; and the work of Joseph Lister on surgical antisepsis (pages 2-9, 13-23 and 33-38).
The fortuitous discovery of penicillin by Alexander Fleming is undoubtedly the most symbolic moment in the history of antibiotics, and the author noted that this landmark was ‘eerily similar’ to Fleming’s previous ‘chance discovery of lysozyme‘. The narrative described how the ‘painfully shy‘ but ‘playful‘ Fleming made his serendipitous observation after he ‘sloppily left Petri dishes containing staph cultures unattended on a bench in his St. Mary‘s lab when he departed for vacation in August 1928’. On his return, the author said Fleming ‘found that one of the Petri dishes had been contaminated…by a fungus‘ around which ‘was a ring in which all the staphylococci had disappeared’. Whilst the author gave credit to Fleming for ‘recognizing the potential of the compound’, and for his subsequent experiments which showed the range of organisms responsive to penicillin, he nevertheless criticised him for his ‘dubious…recollections of the discovery’, and for failing to demonstrate penicillin’s curative power. The public reaction to the discovery of penicillin also featured prominently in the story which described how the breakthrough made Fleming a hero (pages 88-94 and 149-150).
A less celebrated but equally worthy pioneer of the penicillin story was Howard Florey, the Australian scientist who the author referred to as ‘the first Rhodes scholar to change the world’ because of his remarkable feat of converting the discovery into practical utility. The book traced Florey’s journey to Oxford where, as director of the pathology unit, he worked alongside such colleagues as the ‘ambitious, confident, and resourceful’ chemist Ernst Chain, and the ‘modest’ Norman Heatley, a man with a ‘great talent for building lab equipment out of spare parts and discards’. The narrative followed the team as they stabilised penicillin, increased its laboratory yield, demonstrated its curative effectiveness, and, with the help of X-ray crystallographer Dorothy Crawfoot Hodgkin, identified its beta-lactam chemical structure – the feature that accounts for both its activity and instability. The author also narrated the intrigue-laden story of how Florey initiated and coordinated the large-scale production of penicillin, all the while aware of the impact it will have on the outcome of World War II. The book’s exploration of the pharmaceutical aspects of penicillin was also revealing, noting as it did that ‘the penicillin project…created an entire industry, and built what would become some of the most profitable companies in history’ (pages 97-112, 118, 125, 129-130, 142-148 and 151-181).
The discovery of streptomycin was another landmark in the history of antibiotics, the book describing it as ‘a miracle‘ against tuberculosis, what it described as a ‘really scary’, ‘highly dangerous’, and ‘very easily spread’ disease with a ‘talent for hijacking the body’s own defences’. The book narrated the streptomycin story on the background of the fractious rivalry that blew up between its co-discoverers, the older and more experienced soil microbiologist Selman Waksman, and his graduate scientist Albert Schatz. The book described how Schatz carried out the gruelling work that isolated streptomycin; how William Feldman and Corwin Hinshaw demonstrated its effectiveness on tuberculosis; and how the pharmaceutical company Merck initiated its mass production. The book also chronicled the bitter controversies and legal battles that emerged over credit and payment rights, and over the award of the Nobel prize to Waksman but not Schatz. Another impressive aspect of the streptomycin story is the British Medical Research Council trial which conclusively confirmed the effectiveness of the drug in tuberculosis. The author specifically described how Austin Bradford Hill, ‘the most influential medical statistician of the twentieth century’, himself a victim of tuberculosis, applied his innovative randomised triple-blind controlled method to this study, referring to it as ‘the first in the history of medicine’. It is also significant that Hill’s follow up trial demonstrated that combining streptomycin with PAS reduced the risk of the development of mycobacterial drug resistance (pages 182-207).
Amongst the other antimicrobials the book reviewed, the discovery of sulfanilamide also stood out for being ‘the world’s first successful antibacterial drug’, and for being made from inorganic material. In documenting this account of sulfanilamide, later named prontosil, the book featured the research of physician and future Nobel prize winner Gerhard Domagk who discovered sulfanilamide whilst working with the pharmaceutical company Bayer. Domagk, the author recalled, demonstrated that sulfanilamide ‘inhibits an enzyme essential for the production of the B vitamin required for folate production in bacteria’. The book also described the work of Paul Ehrlich, ‘one of the most respected physicians and scientist’, who investigated the effect of dye-based agents on trypanosomiasis. Other antibiotic breakthroughs the book recounted included the discovery of erythromycin, ‘a powerful weapon in the battle against infectious diseases’, by Abelardo Aguilar, and the discovery of aureomycin, the first tetracycline, by Benjamin Dugger. The discovery of chloramphenicol was another landmark the book depicted especially in view of its effectiveness against typhus – what the author depicted as ‘a scourge of humanity’ (pages 39, 52, 60-77, 214-254).
Antibiotics remain at the core of contemporary clinical, laboratory and pharmaceutical practice, and this book provides an awe-inspiring account of the impact they have had on clinical practice. With a balanced perspective, the author narrates a whirlwind historical journey which highlights the value of research in solving even the most daunting medical conundrums. The book also conveys the lesson that collaboration, knowledge and serendipity are key drivers of many seminal medical discoveries. This is an inspiring and enlightening book and I recommend it to all doctors.
Publisher, Place, Year: Penguin Books, New York, 2017
Number of chapters: 9
Number of pages: 358
Star rating: 4