In Memoriam: Karl M. Johnson, MD

Posted 16 November 2023

By Thomas P. Monath MD, FASTMH
ASTMH President, 2005

On October 10, 2023, we lost the legendary virologist Karl M. Johnson, MD, President of ASTMH in 1984.

Karl gained worldwide recognition for his pioneering work on viral hemorrhagic fevers. It is perhaps ironic that Karl began his fabled career working on the most innocuous of human pathogens (rhinovirus common colds) before addressing the most dangerous and lethal viruses. Karl was a leader, teacher and raconteur extraordinaire who inspired, mentored and nourished a legion of scientists and arbovirologists. It is not difficult to sum up his brilliance: He synthesized a unique and broad understanding of the natural world, biology and virology, and intuitively devised innovative experimental and observational approaches based on big concepts and innovative ideas. His accomplishments still stand today as fundamental to our understanding of the ecology, pathogenesis transmission and variation of multiple virus groups: alphaviruses, hantaviruses, arenaviruses and filoviruses.

Karl was born in Terre Haute, IN, and attended Oberlin College in Ohio, graduating in 1950. He gravitated toward science and medicine and matriculated at the University of Rochester School of Medicine. After medical school, he trained in internal medicine at Columbia-Presbyterian Hospital (1956-1958). The doctor’s draft required two years of service, and Karl obtained a commission in the U.S. Public Health Service and was assigned to the laboratory of Robert Chanock at NIAID, where he worked on respiratory viruses: parainfluenza, adenoviruses and rhinoviruses. There, he also met his future second wife, Patricia Webb, MD, who also became his partner in the laboratory and made her own historical mark in the history of arboviruses and hemorrhagic fevers.[i] 

A Turning Point
A turning point came in 1962, when Alexis Shelokov MD (1919-2016), who had taken on the directorship of NIH’s Middle America Research Unit (MARU) in Panama, offered Karl a position. This was to be a 3 ½ year assignment in what might be considered a scientific boondocks, but turned into an astonishingly productive 13 years, during which time Karl succeeded Shelokov (in 1964) as Director and built a center of excellence in arbovirology.  The event that set in motion Karl’s career was the investigation of an epidemic of hemorrhagic fever in a remote corner of Bolivia. This required an extremely challenging logistical operation, in which he brought the laboratory to the field and set up a primitive BSL-4 system to support clinical and field studies. In addition to uncovering details of the human disease, Karl and his team determined the mode of spread and transmission of the causative virus from rodents to humans, established a hamster colony, isolated the virus (naming it after the nearby Machupo River), showed it to be related to the etiologic agent of Argentine hemorrhagic fever, and developed a rodent control strategy that brought the outbreak to an end. Early in this work Karl (and Pat Webb) contracted Bolivian hemorrhagic fever, from which they recovered.

Karl’s accomplishments at MARU in the years that followed are too numerous to detail here, but it is important to recognize the enormously talented people he brought together to build a comprehensive scientific program that crosscut the disciplines of epidemiology, entomology, vertebrate ecology and virology, producing many leaders in tropical medicine: Ron Mackenzie, CJ Peters, Jim LeDuc, Laura Kramer, Robert Tesh, Byron Chaniotis, Nat Young, Pat Peralta and Gerry Eddy, to name but  a few.

I recall meeting Karl at the beginning of my career at CDC in 1969, when I was engaged in my first overseas assignment during an epidemic of Venezuelan equine encephalitis (VEE) in Ecuador. The hospital in Guayaquil were filled with children on respirators (iron lungs at the time), clinging to life with viral encephalitis. Karl opened my eyes to the unprecedented scope of this tragic outbreak and to a wider set of unanswered questions about the disease, the virus and its ecology, and he thereby influenced the direction of my future career. During the 1969 outbreak, which eventually extended through Central America to Texas, Karl showed that a live, attenuated vaccine strain (TC-83) developed by USAMRIID for protection of humans, was safe and effective for horses, which played a critical role as amplifying hosts for mosquito vector infection and transmission. Moreover, the vaccines produced in veterinary facilities in South America at the time, consisting of formalin-inactivated virus, were considered by Karl to be possibly related to the cause of the outbreak (due to incomplete chemical inactivation). This spawned an effort at MARU to classify the VEE complex using a kinetic hemagglutination-inhibition technique with Proechimys  (spiny rat) immune sera, a study with Nat Young for whom an ACAV award is named[ii], one practical aspect being the identification of the natural or artificial source of VEE outbreaks.

Figure 1. Karl Johnson in CDC BSL-4 laboratory, Centers for Disease Control, Atlanta GA ca. 1975
In 1975, Karl joined the CDC, where he founded the Special Pathogens Branch.  At CDC, Karl re-designed the existing cabinet-line BSL-4 unit that had been built in response to the 1969 Marburg virus incident, creating a modern positive-pressure suit lab (Figure 1) for work on hemorrhagic fever viruses, including Lassa fever, a relative of Machupo virus. A year after joining CDC, Karl established a research center in Kenema, Sierra Leone for isolation and study of patients with Lassa fever, led by Joseph B. McCormick MD (1942- ) who went on to be a renowned epidemiologist and educator. A seminal contribution of McCormick’s work in Kenema was the conduct of a controlled trial of intravenous ribavirin, showing efficacy in ameliorating severe disease. In addition to the work on Lassa virus, Karl collaborated with the South Korean physician-scientist Ho Wang Lee MD (1928-2022)[iii] to uncover the etiologic agent of hemorrhagic fever with renal syndrome, which had plagued U.S. troops during the Korean conflict, once again naming it after a river (Hantaan).

An Apogee in Hemorrhagic Fevers 
Perhaps the apogee of Karl’s adventures in hemorrhagic fevers came in 1976, when an unprecedented large epidemic occurred in Zaire and Sudan involving over 300 cases, of which 90% were fatal. Karl led the international commission of investigation, together with colleagues from Belgium and the United Kingdom investigating the epidemiology and etiology of this dramatic episode of an unknown disease.  The new agent was found to be similar in morphology to Marburg disease virus[iv]. Ebola virus was named for a river so as to avoid stigmatizing the epicenter town, Yambuku.  Apart from the fascinating scientific discoveries, which foreshadowed a much larger Ebola outbreak in West Africa in 2013-2016, the events of 1976 were dramatized by extraordinary strategic and logistical difficulties, infections and deaths among the investigators and medical care personnel, challenges of containment and control, uncertainty of the natural host or vector, and lack of specific countermeasures. Karl’s organizational skills and leadership and focus on research through these events were critically important. In 1981 Karl moved to USAMRIID to head up their program on viral hemorrhagic fevers. There he oversaw a well-resourced, integrated program of research on diagnosis, vaccine and antiviral development, pathogenesis and molecular structure of a number of BSL-4 agents.
Between 1984 and 1987, Karl moved to the biopharmaceutical sector, first at Hoffmann-LaRoche and the at Viratek Inc., where he focused his efforts on antiviral drug development and clinical research and especially on ribavirin, which had proven useful in the treatment of Lassa fever but was also the leading treatment for respiratory syncytial virus disease. In a sense he had come full circle back to respiratory viruses, but I am sure he did not see it that way, but rather as an opportunity to extend his breadth of experience to develop clinically useful technologies.

In 1991-92 Karl briefly worked on HIV drug trials, and then became an independent consultant. He served as Advisor to State and National health centers on Hantavirus, Ebola, and other infectious diseases and as an advisor to the governments of Canada, Australia and U.S. in the design and use of BSL-4 laboratories for medical and animal disease research.  He chaired a peer review group assisting with design of first high-containment laboratory in an academic center in United States (University of Texas Medical Branch, Galveston) and chaired a scientific peer review group at the Rocky Mountain Laboratory BSL-4 facility design project (NIAID).

Honors and Scientific Recognition
Among Karl’s many honors and scientific recognition, he was awarded the Bailey K. Ashford medal and the Walter Reed medal from ASTMH; the Order of the Condor, Government of Bolivia, 1964; the Gorgas Medal, Association of Military Surgeons, Washington, D.C., 1969; the Civil Merit with Gold Palm Award, Government of Zaire, 1980; the Richard M Taylor Award, Committee on Arboviruses, ASTMH, 1987; the Kilby Laureate Foundation, Lifetime Achievement Award, Dallas, October 1998; the Manuel Amador Guerrero medal, Government of Panama, 2001; and the International Hero Award, UC Berkeley School Public Health, March 2001. He has served on the Faculties of the University of New Mexico and Tulane University.
Figure 2. Karl with a very large bull trout caught during the salmonfly hatch on the Blackfoot River in Montana, 2010. Courtesy Marshall Bloom

Karl had a life-long passion for flyfishing and spent much of his leisure time pursuing trout. When whirling disease, caused by a myxosporean parasite, decimated trout populations in Montana in the mid-1990’s, Karl effectively leveraged his contacts and expertise in emerging infectious diseases to help address this problem. He helped found the Whirling Disease Foundation and recruited other prominent scientists, like Stanley Falkow, to assist in developing research agendas, fisheries management strategies and educational efforts.

There are a number of published accounts of Karl’s extraordinary career[v],[vi], but for those wishing to see him tell his story first-hand, nothing surpasses the ASTMH Workers in Tropical Medicine series hosted by Barney Cline, which reveals much about Karl Johnston’s personality and life’s journey.

Karl is survived by his wife, Merle Ann Johnson, his son David F. Johnson, wife Corine Samwel, and their three children Ian (Agnes), great-grandson Maxwell, Nathan (Vanessa). great-grandson Vincent, and Laura (Cole); daughter-in-law Laurie St. Laurent and her children, Katie (Nicholas), great-grandson Keegan and great-granddaughter Ellen, and Kraig (Megan); son-in-law John Cushman (Mary-Sue) and grandson Evan, as well as his wife Merle's children: daughter Diane Kirby and husband Tom, and their daughter, Alanna, son Douglas Kuehne, and his daughter Jennifer.
Karl was preceded in death by his daughter Melissa, son Kurt, brother Bruce, and sister Ellen.

Acknowledgements: Thanks to Pierre Rollin, Joseph McCormick, Marshall Bloom, Thomas Ksiazek, Fred Murphy and others for reminiscences and advice.

[i] Monath TP and Johnson KM. In Memoriam, Patricia Ann Webb (1925-2005). Arch Virol 2005;150:1268-1270.
[ii] Young NA, Johnson KM. Antigenic variants of Venezuelan Equine Encephalitis virus: Their geographic distribution and epidemiologic significance, American Journal of Epidemiology, 1969; 89:286–307
[iii] Bagcchi S. Ho Wang Lee. Lancet Infect Dis 2022;22:1431.
[iv] Breman JG, Heymann DL, Lloyd G, McCormick JB, Miatudila M, Murphy FA, Muyembé-Tamfun JJ, Piot P, Ruppol JF, Sureau P, van der Groen G, Johnson KM. Discovery and Description of Ebola Zaire Virus in 1976 and Relevance to the West African Epidemic During 2013-2016. J Infect Dis. 2016 Oct 15;214(suppl 3):S93-S101
[v] Johnson KM. Zoonotic diseases--an interview with Karl M. Johnson, M.D. by Vicki Glaser. Vector Borne Zoonotic Dis. 2001 Fall;1(3):243-8
[vi] Reeves WC. Introduction of the President, Karl M. Johnson. Am J Trop Med Hyg. 1985 Jul;34(4):653-4.