images of science in the 21st century may well be that of the coronavirus, a deceptively simple spherical object with a surface covered by spikes. The havoc the COVID-19 pandemic has caused will remain etched in memory for decades to come. The principal actor in the ongoing drama, the coronavirus (the virus family to which severe acute respiratory syndrome coronavirus 2, or SARS CoV-2, belongs), was unknown to the world of science until the mid 1960s. Other viruses that caused respiratory disease, notably the influenza virus and the common cold virus (rhinovirus), were better known. Who then can legitimately claim to be called the discoverer(s) of the coronavirus? In seeking an answer to this apparently simple question, I chanced upon the work of Dorothy Hamre, a virologist and infectious disease researcher at the University of Chicago’s Department of Medicine. In a paper co-authored with John J. Procknow, Dorothy Hamre describes a new virus “possibly associated with mild upper respiratory illnesses of man” ((1966): Proceedings of the Society of Experimental Biology and Medicine , Vol. 121, pp. 190-3).
Dorothy Hamre was the first person to isolate a strain of the coronavirus, which she did from samples taken from students at the university’s medical school. This strain was designated as 229E. Almost at the same time, in Britain’s Common Cold Research Unit in Salisbury, David Tyrrell and Malcolm Bynoe were isolating what appeared to be a new class of viruses from organ cultures, with the strain B814 appearing to resemble an avian bronchitis virus. In 1967, June Almeida, working in Tyrrell’s laboratory, produced the first image of the virus. Transmission electron microscopy revealed particles “varying somewhat in size” with “an average diameter of about 800 to 1200 angstroms [which is denoted by A (1 A = 10-8 cm)]. The surface of the particles is covered with a distinct layer of projections roughly 200 A long. These projections seem to have a narrow stalk just within the limit of resolution of the microscope and a ‘head’ roughly 100 A across.” Much of the world’s population can now recognise an idealised rendering of this image. It was only in 1975 that the virus was christened. A group of scientists that did not include Dorothy Hamre but featured both Tyrrell and June Almeida made a proposal “to group together a number of recently recognised viruses under the head of coronaviruses” ((1975): Intervirology , Vol. 5, pp. 76-82). Thus was the coronavirus launched in the literature of virology and medicine.
Who was Dorothy Hamre? A search for the face behind the name led me through the labyrinths of the Internet and launched me into correspondence with an academic at Harvard University and an archivist in Arizona. The Internet yielded much in the way of Dorothy Hamre’s science but little in the way of personal details. A search with Google Scholar yielded 56 publications spread over the period 1941-72. PubMed, the database of the United States’ National Library of Medicine, turned up 40 papers between 1943 and 1972. Clearly, Dorothy Hamre was a consistent and productive scientist, at a time when scientific publications appeared when authors had something to say and not, as in more recent times, as an essential prerequisite for career advancement. I was drawn to her early papers far removed from the coronavirus. One written in 1943 with the intriguing title “The toxicity of penicillin as prepared for clinical use” reported on the death of guinea pigs during experiments on the efficacy of the newly introduced antibiotic on gas gangrene. In later years, a commentator was to note of this study that Dorothy Hamre’s admonition that the “chronic toxicity (of penicillin) for man be borne in mind” was an “accurate and perceptive observation” (Botting, J.H. (2015): Animals and Medicine , Open Publishers, p. 181). The Second World War was at its most intense, and penicillin, the newest weapon against battlefield infections, was still far from being a homogeneous chemical substance. Even a cursory reading of Dorothy Hamre’s papers reveals that her work had the attention to experimental detail that is so characteristic of a skilled and careful laboratory scientist. When she turned her attention to respiratory viruses in the 1950s, she was well positioned to address the problem of isolating the infectious agents that cause respiratory disease.
Her research led her to the coronavirus 229E. A paper she co-authored with Marc Beem of the Department of Pediatrics, University of Chicago in 1972, entitled “Virologic studies of acute respiratory disease in young adults: V. Coronavirus 229E infections during six years of surveillance”, was an epidemiological analysis of the infections caused by the virus she had discovered ((1972): American Journal of Epidemiology, Vol. 96, p. 94).
Anonymous presence
But who was Dorothy Hamre? Her scientific work is available for all to see. Yet, she is an almost anonymous presence on the Internet. The book The Foundations of Virology (Frederick A. Murphy, Infinity Publishing), which was published in 2014, provides a honour roll of the scientists who advanced the discipline and celebrates “Discoverers and Discoveries, Inventors and Inventions and Developers and Technologies”. I scanned the list, which begins centuries ago, and scrolled down to 1965, where I found that the “discovery of coronaviruses” was credited to David Tyrrell, June Almeida and others. Even here, Dorothy Hamre had been consigned to anonymity. Had I been chasing a mirage, driven by the boredom of the coronavirus-induced lockdown? The Internet and Google, as always, threw me a lifeline.
Dorothy Hamre’s name appears in the archival collections of the Cline Library at Northern Arizona University, Flagstaff, Arizona. For one whose academic affiliations were in locations such as Colorado, Washington State, New Jersey and Chicago, Flagstaff—a town that lies near the intersection of the Rocky Mountains and the vast reservations to which Native Americans have been consigned and not too far from the Arizona desert—seemed a strange resting place. But it was here, in a collection of photographs of nature deposited by her husband, Alexander Brownlee, that I found a brief biographical note: “Dorothy Hamre was born in Seattle, Washington, in 1915. She earned her B.S. cum laude in 1937 and her M.S. in 1938, both from the University of Washington. Her PhD in virology came in 1941 from the University of Colorado. She was a bacteriologist with the 9th Corps Area Lab in Fort Lewis, Washington, from 1941 to 1942 and then associate in research at the Squibb Institute of Medical Research in New Jersey from 1942 to 1951.
“During 1951-1952 she worked as a bacteriologist for the Army Chemical Corps at Dugway Proving Grounds near Tooele, Utah. She became a research associate and Assistant Professor in the Department of Medicine, University of Chicago, in 1952, where she remained until 1968.” She retired in the late 1960s, prematurely for an academic, and went to live in the small town of Ouray, high up in the Rocky Mountains in Colorado. From the archivist in Arizona, I received a brief excerpt from a book, San Juan Country by Thomas M. Griffiths, that gave me a glimpse of her life in Ouray. In a strange way, the extract said little but seemed to say it all: “To come into Alex and Dorothy Brownlee’s home and enjoy their hospitality and the ambiance which surrounds their past academic and artistic pursuits is to escape into an intellectual realm not often found on what remains of the Western frontier.” Dorothy Hamre Brownlee died on April 19, 1989, in Ouray.
The coronavirus strain she discovered, 229E, is generally relatively benign, causing moderate infections, but in rare cases serious, life-threatening conditions can quickly arise, as reported in a recent example from Greece (“A Rare Case of Human Coronavirus 229E Associated with Acute Respiratory Distress Syndrome in a Healthy Adult”, Case Reports in Infectious Diseases , Vol. 2018, Article ID 6796839). This case was highlighted in the popular press (https://www.forbes.com/sites/alexknapp/2020/04/11/ the-secret-history-of-the-first-coronavirus-229e/ #654eae3871d6).
More than 30 years after Dorothy Hamre’s death, the coronavirus has become a household name, and terms such as “social distancing, lockdowns and flattening the curve” roll with easy familiarity off the tongues of leaders and common people. The SARS and Middle East respiratory syndrome episodes of the first decade of the 21st century served as warnings of the potential lethality of coronaviruses. The visionary statesman of science Joshua Lederberg warned us in 1989: “No matter how selfish our motives, we can no longer be indifferent to the sufferings of others. The microbe that felled one child in a distant continent yesterday can reach yours today and seed a global pandemic tomorrow. Never send to know for whom the bell tolls; it tolls for thee.”
Dorothy Hamre spent much of her life working on infectious diseases and discovered the coronavirus. As a woman building a scientific career in the days of the Great Depression and the Second World War, she must have been gifted with both imagination and resilience. She must have honed her experimental skills in the hard crucible of infectious disease laboratories. As the coronavirus rampages across continents, Dorothy Hamre emerges as a distant and anonymous presence. As the archives in Arizona are locked down, the virus will decide when we get to see an image of its discoverer. While thinking about this unsung scientist, an old dictum, whose provenance is uncertain, came to mind: “Time and history blot out small merit and fatten big glory.”
P. Balaram is at the National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bengaluru.
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