The monumental endeavour to develop the yellow fever vaccine is a reminder that scientific leadership is not built overnight. It is cultivated, often at great cost and with long vision. (Photo: iStock) 
Max Theiler is the first of 13 South Africans to receive a Nobel Prize (1951, physiology and medicine) for developing what became known as an attenuated vaccine for yellow fever. His discovery changed the course of medicine as it treated, cured and prevented the deaths of thousands upon thousands of people. His Swiss-born father, Sir Arnold Theiler, was the inaugural director of the Onderstepoort Veterinary Research Institute outside Pretoria.
Theiler’s discovery, developed while he was researching at the Rockefeller Foundation laboratories in New York, was a breakthrough answer to the challenge the US Army had in protecting their soldiers against yellow fever. Military medical data from the Spanish-American War of 1898 revealed that more soldiers died from disease than in battle. Of these, yellow fever was among the most devastating, following a swift and virulent course.
In response to this urgent threat, the US Army chose to mobilise science. In 1900, army surgeon Walter Reed, namesake of the Walter Reed National Military Medical Center, was appointed to lead the Yellow Fever Commission in Cuba. Under his leadership, the commission confirmed that mosquitoes were the primary vector of transmission, not “miasma” or direct contact, as previously believed. In doing so, Reed and his team also pioneered a new ethical standard for human subject research by seeking and documenting informed consent.
The results were staggering. Armed with this new understanding, the US occupation forces initiated mosquito control efforts that eradicated the yellow fever epidemic in Cuba within 150 days. Their success not only saved lives – it unlocked possibilities. It made the construction of the Panama Canal feasible. It altered the trajectory of American expansion and cemented public health as a strategic asset.
However, the army’s work was not the end of the story. Yellow fever remained a persistent threat because, although its transmission had been hindered, the lethality of the disease was not. American leadership and funding, most notably from the Rockefeller Foundation, sustained the momentum necessary to better understand and combat the disease. In 1927, Adrian Stokes and collaborators at the foundation’s laboratory in Nigeria showed that monkeys could be infected with material from humans with yellow fever, confirming the viral nature of the disease. And while the foundation played a crucial role, this was still part of a larger American-led public health initiative, initiated by the army’s urgency and sustained by a national commitment to medical progress.
The culmination of this decades-long effort came in the 1930s with the work of Max Theiler, whose breakthrough would change the course of medicine. Theiler developed a method to weaken the yellow fever virus through repeated incubation in chicken embryos. Between the 89th and 114th incubations, a viral strain emerged that no longer caused disease in humans but still conferred immunity. This weakened virus, known as 17D, became the foundation of one of the most successful vaccines yet developed. It remains in use today, nearly a century later. Theiler was subsequently awarded the Nobel Prize in Physiology or Medicine in 1951 – an honour shared not only by him but, implicitly, by the American institutions that made his work possible.
Why tell this story now? Because it is a reminder that scientific leadership is not built overnight. It is cultivated, often at great cost and with long vision. The US Army’s urgent wartime response sparked a decades-long scientific relay from battlefield hospitals in Havana to laboratories in west Africa and New York. A primary driver of this monumental endeavour was a shared sense of responsibility that America, having the means and knowledge, should use its resources for the good of all.
That sense of responsibility is now waning. Public health infrastructure is underfunded both domestically and globally. Vaccine scepticism is no longer a fringe belief. Institutions that once led the world in biomedical innovation are facing political headwinds and budget cuts. If we forget the yellow fever story, we risk forgetting what made that success possible in the first place: institutional investment, international cooperation and a belief that the health of others is tied to our own.
The development of the yellow fever vaccine stands as a landmark achievement in both medical science and American history. It is a prime example of the long-term institutional dedication of the US in the field of public health. Had it not been for continued American funding and prior expertise, Theiler’s vaccine might not have been possible. America’s part in vaccine development should not be understated or forgotten. Speak to the US Army about its historical importance in protecting their soldiers’ health and for the developing the Panama Canal.
South Africa’s part too. A country of mining and agriculture, the country has been at the forefront in developing vaccines to confront animal diseases such as foot-and-mouth and rinderpest. Onderstepoort is legendary for its animal health capabilities, being a training location for generations of veterinary experts and a vital research site for what is, after all, a globally linked enterprise. The US, South Africa and indeed all existing and emerging vaccine manufacturing ecosystems, must upscale capabilities and strengthen science collaborations to take the greatest contribution to advancing health in the modern era – vaccines – to a genuinely global level before the next pandemic hits. DM
Dr Wilmot James is a professor and senior adviser, Andrea Uhlig a research associate and Brendan Beng an intern at the Pandemic Center, School of Public Health, Brown University. James is co-editor (with the late Kader Asmal and David Chidester) of and contributing author to South Africa’s Nobel Laureates: Peace, Literature, Science (Johannesburg, Jonathan Ball, 2004) featuring Max Theiler.