Lectures

The scientific entrepreneur as hero: from Arrowsmith to the covid-19 vaccines

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Cover Arrowsmith, Pocket Books, 1944 Edition

Sinclair Lewis’s novel Arrowsmith, published in 1925 to critical and public acclaim (the book was awarded the Pulitzer prize, although Lewis refused it), is a bildungsroman with an unusual hero: a young doctor cum scientist, Martin Arrowsmith (Lewis, 1925). The hero’s career includes a range of roles and positions: he is at different times a country doctor, a public health expert, a practitioner in an upscale clinic, a researcher in a cutting-edge institution, a brave fighter against epidemics in the tropics (where his beloved first wife dies tragically), and later a well-respected scientist married to a rich, second wife. At the end of his long trajectory Arrowsmith heroically rejects the false trappings of wealth, fame and success as a leading scientist at the McGurk Institute (a thinly-veiled fictional representation of the Rockefeller Institute, New York) to devote himself to the pursuit of disinterested scientific knowledge in the wilderness of Vermont. 

Arrowmith was written by Sinclair Lewis in close collaboration with a young doctor and researcher, Paul de Kruif. After his medical studies, de Kruif chose a scientific career and specialized in microbiology. When demobilized from service in the Army Sanitary Corps during the First World War, he was hired by the Rockefeller Institute, where he worked with the famous biochemist Jacques Loeb. De Kruif however became rapidly disillusioned with the Institute and with the state of medical research in the US, and in early 1922 he published, under a pseudonym, a series of critical articles in the Century Illustrated Monthly, under the title “Our medicine men by one of them.” As a result, he lost his job. A chance meeting with Sinclair Lewis, then looking for a suitable topic for his next novel, led to close collaboration between the two men. Lewis did the writing and de Kruif’s taks was to supply the scientific background. In all probability, though, he also had an important input on the image of medical research such as it appears in Arrowsmith (Hutchisson, 1992). In 1926 De Kruif published his best-selling book The Microbe Hunters (New York: Harcourt Brace & Company Inc.), that told the history of microbiology as an spellbinding adventure. The book invented an entirely new form of writing about science: it inspired generations of young people to became  medical researchers. It also open the way to De Kruif’s highly successful career as writer and popularizer of science.

One of the key themes of Arrowsmith, one that might have been directly inspired by de Kruif, is the glorification of science as a passionate and disinterested search for knowledge. In a seminal text of 1963, the historian of medicine Charles Rosenberg argues that Martin Arrowsmith is presented as a prototype of the American hero and his itinerary represents a quintessential American quest for meaning (Rosenberg, 1963). This itinerary faithfully mirrors different aspects of medicine: private and hospital practices, public health, domestic and international interventions. It culminates with Arrowsmith’s full adherence to the austere ideal of pure science, propagated by his teacher, the German researcher Max Gottlieb, a modern-day saint of the religion of science. (Gottlieb is partly modeled on de Kruif’s mentor at the Rockefeller Institute, Jacques Loeb). At the end of the novel Arrowsmith and his colleague Terry Wickett abandon the hypocrisy of the temple of cutting-edge scientific research, the McGurk Institute, and establish a small laboratory in Vermont dedicated to fundamental biological research. Only the pursuit of disincarnated scientific knowledge, incommensurable with the corruption-prone aspects of medical practice, can save American medicine. Science is not a profession, not even a vocation, but a religion. This view is displayed in Arrowsmith’s oft quoted prayer of the scientist:

God give me unclouded eyes and freedom from haste. God give me a quiet and relentless anger against all pretense and pretentious work and all work left slack and unfinished. God give me a restlessness whereby I may neither sleep nor accept praise till my observed results equal my calculated results or in pious glee I discover and assault my error. God give me strength not to trust to God! (Lewis, 1925, ch. 26) 

In his 2001 analysis of the book, the physician and historian of medicine Howard Markel proposes a somewhat different view of the book. Lewis, Markel argues, depicts in Arrowsmith an ideal of medical science, one not grounded in rejection of the clinics but rather in a creative combination of fundamental and clinical/public health knowledge. Markel does not see Martin Arrowsmith only as a personification of the ‘pure’ scientist, but as a living incarnation of the conflict that continues to trouble doctors and their patients today as well. It is not clear who is presented in the book as more important in the conquest of disease: the compassionate, sympathetic healer, caring for sick individuals and affected communities, or the cold, obsessive investigator, trying to ascertain the cause of disease and eliminate it, which, if successful, would make clinicians and public health experts obsolete (Markel, 2000; Markel, 2001). The German bioethicist Heiner Fangreau also believes that Lewis does not categorically reject the point of view of medical practitioners, be they compassionate physicians or devoted public health experts. He does present the approaches of fundamental scientists and medical practitioners as incommensurable, but does not claim that the first are more important than the second (Frangeau, 2006). The historian of medicine Etienne Lepicard proposes that the novel not only displays the tension between scientific and medical ethics but also points to a possible way of overcoming this tension through the production of basic scientific knowledge that can benefit suffering humanity (Lepicard, 2007). 

Arrowsmith’s trajectory indeed ends with a firm commitment to the ideal of pure science, yet he also displays a keen interest in other aspects of medicine. As a student, Arrowsmith appreciated the skill and the humanity of his teacher at the University of Winnemac, the clinician Dean Silva. He performed a decent job as a country doctor in Wheatsylvania, North Dakota, and then his admiration for the public health activist, Gustav Sondelius, led him to employment in the public health department of Nautilus, Iowa. During his short tenure as a public health official, Arrowsmith strived to introduce efficient public health measures. Alas, his zeal in imposing these rules attracted the ire of Nautilus’s notables, and he lost his job. Finally the high point of the novel – the episode of plague on a tropical island – vividly displays the contrast between medical practice and fundamental research (Löwy, 2010). The lessons of this episode are far from being obvious. 

The incident of plague on a tropical island was from the very beginning designed to be the dramatic focus of the book. It was also central to the writing of the novel. In January 1923 Lewis and de Kruif took the steamer S.S Guiana for an extended tour of the West Indies. The main goal of this voyage was to gather material for the plague episode. The trip was the high point of their collaboration. At its end, Lewis had a detailed plan of over 60,000 words for the future novel and a thick notebook full of specific details, especially about the plague episode (Hutchisson, 1992). This episode is centered on the conflict between the physician’s duties as a healer, that is his obligation to his patients here and now, and his duties as a researcher, that is his obligation to future patients. Working at the McGurk Institute, Arrowsmith discovers that a biological agent, the bacteriophage, is able to destroy pathogenic bacteria. The directors of the McGurk Institute give him an opportunity to test the practical value of the bacteriophage therapy in a plague-stricken island. Arrowsmith’s mentor, Max Gottlieb, strongly believes in the importance of rigorous testing of new therapies. His firm adherence to this principle leads to the loss of his lucrative job with the pharmaceutical company, Dowson Hunziker. Gottlieb persuades Arrowsmith to conduct a controlled experiment on the island: half of the population will receive Arrowsmith’s preventive treatment, while other half will be denied it. A rigid application of experimental principles in the midst of a humanitarian disaster sets the stage for an ultimate confrontation between a well-intentioned but often muddled medical practice and the cold principles of scientific medicine.

Once on the island Arrowsmith’s strong commitment to conducting a controlled experiment with a preventive drug is contrasted with the attitude of his former hero, the public health expert Gustav Sondelius, who is opposed to scientific experimentation during a sanitary emergency and refuses to take the bacteriophage if it is not given to everybody else on the island. Sondelius’s consequent death from plague may be seen as no less heroic than Arrowsmith’s insistence on conducting a methodologically rigorous experiment in extreme conditions and thereby facing criticism and pressure. Following the shock of Sondelius’s death, and then that of his wife, Leora, Arrowmith is led to abandon his experiment. He finally gives the bacteriophage to anyone who asks for it. The epidemic finally ends, but it is not clear why. The disappearance of the plague might have been the result of Arrowsmith’s distribution of the bacteriophage, but also of Sondelius’s efforts to improve sanitation and eradicate rats. Old fashioned public health measures, Arrowsmith recognizes later, might have been as important, or perhaps even more important, as his innovative treatment.

Arrowsmith’s final decision to leave the McGurk Institute is fueled by the dissonance between his own and his hierarchical superiors’ interpretation of the plague incident. Arrowsmith himself sees his decision to distribute the bacteriophage to everybody as a betrayal of his and Max Gottlieb’s ideals. The directors of the McGurk Institute have a diametrically opposed point of view. They present Arrowsmith as a heroic scientist who has ended a dangerous epidemic. The Institute leaders do not wish to make material profits from Arrowsmith’s therapy but are very interested in obtaining symbolic benefits – an increase of the prestige of their institution and of American science, and support for America’s political aims. The press and the politicians glorify the McGurk Institute’s intervention on the island, and Arrowsmith’s role in that intervention, as an example of the US’s benevolent policy towards its ‘little brothers’ in Central and Latin America (Jung, 2016a; Jung, 2016b). The final result is however not very different from the practices of dishonest pharmaceutical firms such as Dowson Hunziker: the abandon of sound scientific principles and long-term goals in an attempt to grab immediate advantages. 

Howard Markel ends his article by regretting that Martin Arrowsmith’s prayer of the scientist, to either confirm his results or discover his error, belongs to a bygone past. Up until recently, medical scientists worked toward the greater good of humankind, and saw the opportunity to contribute to the battle against illness as a sufficient reward. But when medical scientists closely collaborate with industry, and there are patent applications to fill out and stock options to consider, one cannot any longer fathom a research scientist praying for anything so noble as the capacity to perceive his error (Markel, 2001). But has the rush for patents – or other forms of commercialization of knowledge produced in the biology laboratory – indeed put an end to the heroic image of the scientist? First, let’s consider Arrowsmith himself. He and Terry Wickett live in a primitive cabin in the Vermont woods, wash themselves with ice-cold water, build a laboratory in a shanty – but produce an environment in which Arrowsmith’s imagination and investigative talents can flourish. Arrowsmith and Wickett plan to extend their laboratory scheme to include eight “maverick and undomesticated” researchers like themselves. In the meantime, they find a way to achieve economic independence through the production of therapeutic sera. Since they sell their sera “rather grudgingly” to physicians of whose honesty they are certain, and refuse the popular drug-vendors, they eliminate intermediaries and, as Lewis’s adds, receive surprisingly large sums – potential seeds of their future success.

Movie poster for “Arrowsmith,” directed by John Ford, 1931.

Arrowsmith ends with an image of a future, successful collaborative enterprise, a community of similarly minded idealistic scientists. The images on covers of successive  cheap paperback editions of Arrowsmith, show a man in white coat peering into a microscope- either alone or with a good looking nurse standing behind him. In both cases, the accent is on science as a solitary activity. John Ford’s film Arrowsmith of 1931, praised for  its faithfulness to the book’s spirit, also depicted Arrowsmith, above all, as solitary, and tortured hero. He is shown, it is true, collaborating with other researchers and doctors, including, surprisingly for a 1931 movie, a highly competent Black physician, but the overall image is the one of the struggles of a lonely, flawed superhuman figure (Lederer 1993; Leteux, 2006).

Research as a passion: a still from “Arrowsmith,” directed by John Ford, 1931.

The anthropologist Paul Rabinow’s book Making PCR may be seen as a continuation of Lewis’ view of science by different means. The book has two heroes. One, Kary Mullis, (Nobel prize laureate for his discovery of the PCR reaction) is an ‘anti-Arrowsmith’: a hedonistic Californian who enjoys surfing, partying and taking LSD, and is very preoccupied with money and fame. But the book’s second hero, Tom White, a senior scientist at Cetus corporation, the biotechnology company that exploited Mullin’s discovery, is an ‘Arrowsmith-like hero,’ whose goal is, “to contribute to a  pragmatic mastery of life’s matter while making a living doing it” (Rabinow, 1996, p. 164). Tom White, one may add, left Cetus when the company was taken over by the Swiss pharmaceutical giant Hoffman-La Roche, and White told Rabinow, Cetus’s  initial creative impulse was weakened by internal struggles and friction. Such a creative impulse was nevertheless very important in  Cetus’s early years. Working in a biotechnology company, White argued, gives scientists much more freedom than they can find in a traditional academic setting. Following White’s logic, Arrowsmith’s and Wickett’s project of a scientific colony in Vermont that would promote “maverick research,” financed through a successful marketing of pharmaceuticals, has the potential to became a site of important scientific and commercial innovation. In the last chapter of Lewis’s book, Arrowsmith’s rural retreat is presented as a “kind of madness.” It might also look like the beginning of a successful start-up.

In 2020 the world has faced a ‘plague’, not on an isolated tropical island but on a planetary scale. Many individuals, institutions, enterprises and countries are engaged in a race to find vaccines and cures for a pandemic. Nearly a hundred years after Lewis and de Kruif traveled to the West Indies on board the steamer S.S Guiana to write a dramatic story of plague fighting, it is again possible to tell stories about researchers’ heroic devotion to the ideal of science. In 2020 there are new elements to this story, above all the amount of money and labor involved in the search for magic bullets (vaccines and therapies), and the size of the profits made by those who find them. Still, in spite of this impressive increase in the scope and scale of goal-oriented research the myth of the heroic and dedicated researcher is still very much alive. Today, however, such a researcher can be a woman and/or an immigrant, s/he does not need to give up family life entirely to enter the priesthood  of science, and s/he can enjoy (in moderation) the material fruits her or his achievements.

One candidate for the role of ‘modern Arrowsmith’ in the Covid-19 era is the British professor of vaccinology at the university of Oxford, Sarah Gilbert, who heads a laboratory which, in partnership with the pharmaceutical firm AstraZeneca, is elaborating one of the main vaccines against SARS-CoV2. This vaccine is based on the relatively new principle of incorporating SARS-CoV2 antigens into an adenovirus. Gilbert is portrayed in the media as entirely dedicated to her vaccine research. From the early days of the Covid-19 pandemic she has slept little, has not taken time off, and has lived only for the goal of producing the Oxford vaccine.  An academic researcher rather than a scientific entrepreneur, she is presented as interested only in the solution of scientific problems, not fame or money. Moreover, she has made an impressive scientific career while being a mother of triplets (now young adults), for many years struggling to balance parenthood with a demanding job (her male partner temporarily gave up his employment to help take care of the children) (Neville, 2020). This image of Gilbert as mother cum scientist may be contrasted with that of Martin Arrowsmith leaving his baby son behind to devote himself to science, and telling him  that he will come to see him again in ten years. 

 Another image of the scientist as a modern – and modest – hero is that of a couple: two researchers of Turkish origin who live in Germany, Ugur Sahin and Özlem Türeci. Turkish migrants to Germany are more often associated with low-level, low-income jobs than with impressive  scientific success: hence the presentation of Sahin and Tureci as “outsiders” but also as an immigration success story. They founded a startup, BioNTech, based in Mainz, Germany, which initially specialized in the immunotherapy of cancer, focusing on the uses of an innovative mRNA-based technology. With the Covid-19 pandemic, Sahin and Türeci saw an opportunity to apply the mRNA technology to rapid production of an anti-Covid vaccine.  They teamed up with the pharmaceutical company Pfizer, and in record time manufactured such a vaccine, the first to be approved in the USA, UK and the European Union. While Sahin is also presented as a successful businessman, Sahin and Türeci are depicted as an ascetic couple devoted above all to science. They live in a modest apartment, do not have a car, and – as for now- have avoided an affluent lifestyle in spite of their recent multi-millionaire status. (Gelles, 2020; Desobnnets et al. 2020). The ‘outsider’ image of the couple Sahin and Türeci has not been tarnished by their association with the pharmaceutical giant Pfizer; this may be contrasted with the depiction of the founders of the second company producing mRNA based Covid-19 vaccine, Moderna, as more ‘traditional’ scientists-cum-entrepreneurs.

But probably the scientist who can be depicted as closest to being a ‘present-day Arrowsmith’ at the origin of an innovative treatment credited with the ability to stop the plague, is Katalin Karikó, pioneer of therapeutic uses of mRNA. Kariko, a molecular biologist who immigrated from Hungary to the US, became ‘obsessed’ by the idea of using mRNA to produce therapies and drugs (Grade and Saltzman, 2020; McKay, 2020; Kennedy, 2020). This sounded like an impossible task, because an external mRNA is rapidly destroyed by the immune mechanisms of the body. Unable to obtain grant money for her research, Kariko lost her tenure track job at the University of Pennsylvania Medical School in the mid-1990s. She was able in extremis to stay in academia and continue her research when she was offered a lower prestige job in the cardiology department of the Medical School of the University of Pennsylvania (in 2019 she was still listed as an adjunct professor there). After ten years of effort, Kariko, with her close collaborator Drew Weissman, a professor at the same medical school, developed a modified mRNA which is not degraded when it enters the body, opening the way to elaborating RNA-based vaccines and therapies. In the meantime, Kariko’s daughter, Susan Francia, became a world champion in rowing and twice an Olympic gold medalist. Articles about Kariko are often illustrated with a photograph of her and her husband, with the daughter exhibiting her Olympic gold (the daughter, we learn, inherited her passion for sport from her parents: Kariko and her husband were marathon runners). This photograph may imply that a devoted scientist need not entirely give up family life or renounce all extracurricular pleasures (Kolleve, 2020). Kariko, who is probably a better researcher than entrepreneur, failed to develop her own biotechnology company. In 2013 she was ‘discovered’ by the couple Sahin and Türeci, who hired her as a senior vice president of their company, BioNTech. Kariko then played an important role in the development of the BioNTech-Pfizer mRNA Covid vaccine, although, as she explained in December 2020, her profits remain modest compared to those of other major players in the field of mRNA vaccines (Kennedy, 2020). 

Martin Arrowsmith, as Charles Rosenberg argues, is a hero not of deeds but of the spirit. He achieves his ultimate triumph through perseverance, unwavering faith in his scientific calling, and adherence to system of values which guide his quest for personal integrity. Like Max Gottlieb, Arrowsmith “is destined for fame, but in a world whose judgments are eternal, international and ultimately untouched by material considerations” (Rosenberg, 1963, p. 452). The key word here is “ultimately.” In our time, biomedical researchers can still be depicted as scientific heroes of the Arrowsmith kind, big pharma and big money notwithstanding. Indeed, The Telegraph’s story of Katalin Kariko, is entitled “Redemption” (Nevey and Nuki, 2020). 


Ilana Löwy is a senior researcher  emerita at INSERM, Paris. Trained as a biologist,  she then retrained as a historian of science. Her main research interest are relationships between laboratory sciences, clinical medicine and public health, material culture of science and medicine, and intersections between gender studies and biomedicine. 


References

Desbonnets, L. D. Boussouar, J. Méchausse. 2020.Ugur Sahin et Ozlem Tureci, les « Curie allemands du covid » à l’origine de la réussite de BioNTech. France 2,2 December, 2020.  

Frangeau, Heiner. 2006. “The novel Arrowsmith, Paul de Kruif (1890–1971) and Jacques Loeb (1859–1924): a literary portrait of ‘medical science.’”Journal of Medical  Ethics, 32: 82–87.

Gelles, David. 2020. The husband-and-wife team behind the leading vaccine to solve Covid-19. New York Times, 10 November, 2020.

Grade, Damian and Jonathan Saltzman. 2020. The story of mRNA: How a once-dismissed idea became a leading technology in the Covid vaccine race. STAT, 10 November, 2020

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Jung, Yeonsik, 2016a.The immunity of empire: Tropical medicine, medical nativism, and biopolitics in Sinclair Lewis’s Arrowsmith.Literature and Medicine, 34, no. 1: 185–206.

Jung, Yeonsik. 2016b. The Rockefeller Institute and American imperialism in Sinclair Lewis’s Arrowsmith. The Explicator, 74:2, 83-87.

Kennedy, Dana. 2020.This scientist’s decades of mRNA research led to both COVID-19 vaccines, New York Post, 5 December, 2020.

Kolleve, Julia. 2020.Covid vaccine technology pioneer: ‘I never doubted it would work’. The Guardian, 21 November 2020.

Lederer, Susan. 1993. Arrowsmith: Film review. Isis,84 (4): 771-772. 

Leteux, Christine. 2006. Arrowsmith: Critique du film. Site DVD Classik, posted 28 June, 2006. https://www.dvdclassik.com/critique/arrowsmith-ford (accessed 18 January, 2021)

Lepicard, Etienne. 2007.La biomedicine à la croisée de la littérature et de l’histoire. Annuaire – EPHE, SHP – 139e année : 302-304.

Lewis, Sinclair. 1925. Arrowsmith,NY: Harcourt Brace& C°.

Löwy, Ilana. 2010. Martin Arrowsmith’s clinical trial: scientific precision and heroic medicine. Journal of the Royal Society of Medicine, 103(11): 461-466. 

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Markel, Howard. 2001. Reflections on Sinclair Lewis’s Arrowsmith: The great American novel of public health and medicine. Public Health Reports,116 (July-August), 371- 375. 

McKay, Robin. 2020. The vaccine miracle: how scientists waged the battle against Covid 19. The Guardian, 6 December 2020.

Neville, Sarah. 2020. Oxford vaccine professor Sarah Gilbert on working as the world watches. Financial Times2 December, 2020.

Newey, Sarah and Paul Nuki. 2020. ‘Redemption’: How a scientist’s unwavering belief in mRNA gave the world a Covid-19 vaccine. The Telegraph, 2 December, 2020. 

Rabinow, Paul.1996. Making PCR: The Story of Biotechnology. Chicago: The University of Chicago Press, quotation p. 164. 

Rosenberg, Charles.1963. Martin Arrowsmith: The scientist as hero. American Quarterly, 15(3): 447-458.

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