Carlos J. Finlay: _{Eradicating yellow fever}

A nomadic student in the time of cholera

Born December 3, 1833, in Puerto Principe, Cuba, Finlay began his life as Juan Carlos Finlay. Finlay’s parents were both European and had moved to Cuba two years before their son’s birth. Trained as an ophthalmologist, Edward Finlay hailed from Scotland and Eliza de Barrés was French, but they had changed their names to Eduardo and Isabel to show their affinity to their new land. Soon, the family moved to the Cuban capital, Havana, where Finlay was educated until age 11, but, like his parents, he would move around the globe. First, he was sent to study in Le Havre in his mother’s native France. There, two years later, he was stricken with cholera. It made him severely ill, but also sparked his initial interest in infectious diseases. Returning to Cuba to recover, he required speech therapy because the cholera had affected his ability to talk. He then went back to Europe but had to avoid France for several months because of the brewing revolutionary movement of 1848. After some study in England and Germany, he did get back to France, this time studying in the city of Rouen, where his father had trained in medicine.

He left France in 1851 because he fell sick again, this time with typhoid fever. Back in Cuba to recover again, he changed his name legally to Carlos Juan. His intention was to become an ophthalmologist like his father, so he hoped to begin medical school. However, due to his switching between colleges in Europe, he wasn't granted a bachelor's degree. This turned out not to be a problem, as there was a country that did not require a bachelor’s degree as a prerequisite for medical study: the United States.

Miasma and fomites

During his early period of medical practice, Finlay developed a reputation as a kind physician who never turned away patients who could not pay. He performed ophthalmic surgery like his father but also practiced general medicine. By this time infectious diseases were his main interest, and this gradually drove him into medical research.

In the mid 19^th century, yellow fever and malaria outbreaks were particularly problematic in Cuba and throughout the Caribbean region, and also in the southern United States. Debates revolved around how yellow fever and other tropical diseases spread, and at first Finlay was just as confused as everyone else. For the transmission of yellow fever in particular, one popular idea was called miasma, referring to chemicals and dirt in the atmosphere as a result of the tropical climate. Another idea involved germs, or microorganisms, attached to fomites – inanimate objects like the surfaces of doorknobs, bits of dirt, people’s hands and clothing, and the legs of crawling bugs. The germ theory of disease was fairly new, but the greatest germ theory advocate was John Kearsley Mitchell, one of Finlay’s professors from Jefferson Medical College.

Under the influence of Mitchell and other professors from Jefferson, Finlay thought that microorganisms could be the reason for many diseases, even possibly yellow fever. Nevertheless, as young researcher in the late 1850s, he initially favored the miasma hypothesis because it associated yellow fever with climate, and clearly the disease occurred only in very warm regions.

Politics complicate the science debate

Finlay’s lifespan coincided with a series of major changes in the political and social environment both within the United States, and between the United States, Cuba, and the rest of the world. As in Cuba and Central America, yellow fever was a major health problem in the southern US, but not in the colder, northern states. Throughout the 19^th century, outbreaks came to the southern US every few years, killing thousands of people.

Prior to the US Civil War, the north and south were divided over the issue of slavery. Most of the science and industry was based in the north, and the northern technical dominance was extreme by the 1850s, when Finlay was studying medicine in Philadelphia. After the war, slavery was no longer a political issue, but the north-south tension and northern scientific edge continued throughout Reconstruction and the period that followed.

Fomites are connected with dirty conditions. Therefore, each time there was an outbreak in the south, northern politicians and scientists would blame it on the southern states. Moving from the mid to the late 19^th century, the fomite hypothesis was favored more and more over the miasma hypothesis, partly because of growing acceptance of germ theory. However, there was also the political factor of being able to criticize filthy conditions down south. Northerners criticized the southern conditions before the war, but also after it was over, since the political division between north and south remained strong.

In parallel with the domestic struggle between the US north and south, for most of the 19^th century, Americans saw Cuba as an eventual US possession. Economically, the Spanish colony was a major source of sugarcane and the rum that was made from it. Cuba is a large island just 90 miles from Florida, so it looked like a better candidate for a future US state than western places like Texas, let alone California and Oregon. And so, ten years before Finlay’s birth, the Monroe Doctrine pointed to Cuba for eventual annexation. At first, northern politicians were worried that Cuba would become a slave state, but this was no longer an issue at the end of the US Civil War. With the southern confederacy defeated, and the Spanish Empire shrinking from revolutions throughout Latin America, the US leadership in Washington had strong ambitions for Cuba. Then, after Cubans attempted, but failed, to gain independence from Spain during the Ten Years War (1868-1878), Spain divested from Cuba – disconnected its empire from Cuba’s sugar economy – as punishment for the revolution. Seeing an opportunity, the US started investing in Cuba to replace Spain.

But while US leaders expected that eventually this would lead to an outright war with Spain, they already considered yellow fever – nicknamed “Yellow Jack” – as potentially a more formidable enemy than any army that the Spaniards could ever muster. Yellow fever was so common in Cuba that most natives of the island were exposed to it as children. Usually, the children didn’t die but instead ended up with partial immunity. During subsequent outbreaks they would get sick, but they wouldn’t die, whereas adult visitors from Spain and elsewhere would suffer fatal consequences. Citing the fomite hypothesis, US researchers blamed Cuban yellow fever outbreaks on dirty conditions just as they did for outbreaks in the southern US. This was the scientific-political setting that dominated Cuba from the 1860s and onward, when Finlay delved into infectious disease research.

Championing a new hypothesis

As he'd done as a student, Finlay also traveled frequently in his medical career, and he took every opportunity to study patients during disease outbreaks throughout the 1860s and 70s. In cases of yellow fever, and also malaria, he noticed one phenomenon that all patients had in common. Virtually everyone afflicted in an outbreak had mosquito bites. Focusing his attention to yellow fever, Finlay reasoned that both the miasma and fomite ideas had to be wrong. Instead, he hypothesized that mosquitoes acted as vectors; they transmitted the unidentified microorganisms that cause yellow fever. All he needed to do was to prove it.

As a first step, Finlay authored a scientific paper proposing a particular mosquito species – called Aedes aegypti today (Culex fasciatus in Finlay’s time). He submitted the paper to the Havana Academy of Sciences in 1865 and became the first researcher to propose mosquitoes as vectors for yellow fever. Six years later, in 1871, he was invited to the US to present the idea, but physicians there and back in Cuba found the hypothesis to be far-fetched compared with the fomite hypothesis. Brushing aside the skepticism from colleagues, Finlay continued his yellow fever research in parallel with his clinical practice. Then, in 1879, British researcher Patrick Manson showed that mosquitoes helped to transmit a worm that caused a horrible disease known as elephantiasis. This encouraged Finlay to take his research to a new level. Showing connections between A. aegypti populations and yellow fever outbreaks amounted to strong evidence, but it also was indirect evidence. To prove that the connection was real, Finlay did something that would be really hard to do today: He obtained healthy volunteers and attempted to infect them with yellow fever.

Through a method that he devised, Finlay inoculated five volunteers with mosquitoes that he considered to be infectious. This resulted in one case of mild yellow fever, and two cases of what he called “ephemeral fever” (very mild sickness that did not last long). The other two volunteers did not become sick and apparently became immune. In 1881, he published his results in a paper, and presented the results both in Cuba and the United States. In the published paper and the presentations, he proposed that the findings in the five volunteers supported his mosquito hypothesis. The rest of the scientific world remained skeptical, however, so Finlay spent the next 13 years expanding on his initial experiments by inoculating more volunteers. By 1894, he had accumulated a plethora of evidence from 90 inoculation volunteers, and from a range of experiments in which he tracked, blocked, trapped, and studied local mosquitoes in connection with different yellow fever outbreaks. All of the evidence pointed specifically to A. aegypti as the vector for yellow fever.

Making headway with the US Army

The skepticism for the idea persisted well into the 1890s, but a small number of health professionals finally did open their eyes, in particular a US Army physician, William C. Gorgas. Following the US victory in the Spanish American War of 1898, Gorgas was appointed as sanitation officer for the US in Cuba. Gorgas had read Finlay’s papers and decided to recruit his Cuban colleague to help with the sanitation efforts, where the elimination of yellow fever, along with malaria, was a prime goal. Havana was plagued once again by a yellow fever outbreak. Physicians throughout the city ordered pans of water to be placed around legs of hospital beds in an effort to prevent crawling bugs. This was because they believed the bugs acted as fomites, carrying yellow fever from infected patients.

But Finlay and Gorgas knew that this was not true. They understood that the sitting water was only providing more spaces for mosquitoes to lay their eggs. Finlay and Gorgas ordered the water pans removed, and this was only the beginning. Effectively, they declared war on mosquitoes throughout Havana. Any pool of water, natural or human made, no matter how small, had to be sprayed with oil, which killed the larvae and kept the mosquitoes from laying their eggs. The mere act of having water sitting around one’s house was declared illegal and punished with a 5-dollar fine. As a result of all of these efforts, yellow fever was eradicated from Havana within a period of three months.

The Panama Canal

As long as no waterway separated North and South America, ships moving between the east and west coasts of North America, Central America, and the northern part of South America had substantially more distance to travel compared with the distance “as the crow flies.” They had to go around the tip of Argentina and Cape Horn at the tip of Chile, but a canal through Central America would reduce the trip by 8,000 miles for ships traveling between the two coasts in the northern hemisphere. The 19^th century had seen the completion of two major canals: the Suez Canal in Egypt and the Corinth Canal in Greece. Technological advances, particularly the invention of the steam shovel, helped these projects greatly. However, a canal through Panama was considered technologically more challenging because the elevation of the land increased significantly between the coasts. Therefore, during the 1850s, a railway was built instead of a canal. Traversing the same geography through which a future canal would need to go, the Panama Railway was completed at the cost of 12,000 lives, most of the deaths due to cholera, malaria, and yellow fever.

Three decades later, the French company Ferdinand de Lesseps made an attempt to build a canal through the same isthmus. The failure of this project resulted partly from fact that technology was still not adequate for any canal through Central America, and also because the plan was for the canal to remain at sea level the whole way through. While the height of the sea is nearly the same on the Atlantic and Pacific coasts of Panama, the land rises as one moves inland, then drops again as one approaches the opposite coast. Excavating the hill country to make a canal sea level the entire way through was not at all practical with technology of the era. Moreover, an even bigger problem was disease. 22,000 canal workers died in the 1880s, mostly from the same diseases that had killed the railway workers, and Ferdinand de Lesseps aborted the project in 1893.

Five years later, in 1898, the Spanish-American war left the US as the undisputed superpower in the region, and American leaders were thinking about continuing where the French had left off. Not only were the American engineers equipped with better technology than the French, including more advanced steam shovels, they also had a different plan. Rather than cutting a sea level canal, the challenges of the terrain could be addressed with an elaborate system of locks and pumps, and the construction of an artificial lake. Moving between the various locks, ships would actually change their altitude, rather than remaining at sea level as the French had intended.

The improved engineering notwithstanding, the Americans were all too aware of what really had befallen the French. No matter how good the new technology, the project would be doomed unless the spread of disease, especially yellow fever, could be prevented. With this in mind, the US government sent the Reed Commission to Cuba, and because of his work in stopping the spread of the disease in Havana, Finlay was named as one of the commission members.

Seeing that the evidence from their tests around Havana (which really were just repetitions of some of Finlay’s earlier work) showed that the Aedes mosquito was indeed the vector for yellow fever, Major Reed and his commission issued their recommendation for Panama. To protect canal workers from yellow fever and malaria, they had to reduce the mosquito population to almost nil. Over the next two and a half years, preparation of the canal zone focused on eliminating mosquito breeding environments. Swamps were drained, wetlands filled in, and Finlay experimented with various chemicals, such as sulfur or pyrethrum, for smoke fumigation. As in Havana, he essentially declared war on mosquitoes and their eggs and larvae in Panama. Gorgas was also involved in the project, and with military efficiency he divided the canal zone into districts, which facilitated careful inspection for sources of sitting water. On top of all of this, the sanitation team ordered that sleeping huts for canal workers must be surrounded with screens to keep out remnants of the mosquito population. Finally, when construction began, in cases when somebody did fall ill, they were quarantined so as not to serve as a source for the spread.

Finlay had an additional idea. In a paper written for the Philadelphia Medical Journal, he called it “a plausible method of vaccination against yellow fever.” In reality, it would not have been vaccination, but a technique that today is called passive immunity. Basically, the method involves using blood, or products from blood, of people who have been infected with yellow fever and subsequently recovered. Using their blood on others would then transmit some immunity. While the immunity idea was not attempted due to implementation of all of the other measures, neither yellow fever nor malaria emerged on the scale it had during the French project. There were cases, but quarantines and the other measures kept them from expanding into an outbreak. Thus, in 1914, the Panama Canal went into service.

Recognition in later life

Gorgas, Reed, and the Panama Canal project as a whole all were given credit for developments that ultimately rested on Finlay’s ideas and work. In fact, Reed was sometimes called the man who “beat yellow fever,” and yet both Reed and Gorgas emphasized Finlay’s centrality to their success. In 1908, France awarded Finlay the Legion of Honor. While he never received a Nobel Prize, he was nominated for it seven times in the category of medicine and physiology. For eight years, the last phase of his career, Finlay held the position of Chief Sanitary Officer of Cuba. He retired in 1909 and lived another six years; today his statue still stands in Panama City near the very canal that his work made possible.