Cutting a 50-mile swath through mangrove swamp and mountains, the Panama Canal was considered the most daring and ambitious engineering feat of its time. But before completion of "the big ditch" in 1914, tens of thousands would die, international tempers would flare, and the biggest villain had to be held at bay.

The story of the Panama Canal is a passionate one. It is the story of an impassioned and persistent struggle against the forces of nature, marked with the blood, sweat, and tears of tens of thousands of laborers. Engineering challenges, political turmoil, and bureaucratic headaches each added its own seasoning to an already spicy and exciting chapter in history.

There were many starts and stops before scientists, sanitary engineers, and canal builders would come to agree that the biggest enemy was actually so small as to pass unnoticed, yet it was so powerful that it very nearly destroyed the centuries-old dream of a passage connecting the world’s two greatest oceans.

Before the canal was finally built, more than 30,000 people would succumb to this tiny enemy--Anopheles and its cousin Aedes aegypti, the mosquitos that carry malaria and yellow fever. The dream of opening a waterway across the isthmus of Panama dates back to 1524, when Emperor Charles V commissioned a study for constructing a canal to link the Chagres River, which flowed into the Atlantic Ocean, with the Pacific Ocean. Charles’ successor, Philip II, quashed the project, however, ruling that "what God hath joined together let no man put asunder."

Interest in the idea waned until the mid-nineteenth century. When gold was discovered in California, the rush was on to find a quicker east-to-west route than the tedious trip around Cape Horn at the tip of South America. France, Great Britain, and the United States--the three world powers at the time--drew up different plans for cutting the distance. One resulted in a 50-mile railway built across the Panamanian isthmus in the 1850s. Here, railroad workers had their first run-in with what canal laborers would later face: malaria and yellow fever waged war on all comers to their tropical soil, and legend has it that one life was sacrificed for every tie laid.

The French were the first to tackle canal-building in Panama. Ferdinand de Lesseps was basking in international glory. He had just completed the Suez Canal, linking the Mediterranean and Red Seas. Successfully joining Asia and Africa encouraged him to repeat the feat. But he soon realized that Panama was not Egypt. He was met with thick jungle vegetation, torrential rains and floods, and oppressive heat and humidity, compounded by vastly different soil conditions than those of the arid desert. Once the digging began, the mosquitos stirred. Their habitat was being dismantled, bringing them in direct contact with canal workers. Yellow fever and malaria killed an estimated 3,500 people a year during the 1881-1889 failed French attempt.

At the time, widespread disagreement existed about what caused these epidemics. One popular belief was the "marsh miasma" theory, which held that the invisible mists and vapors given off by swamps and decaying organic matter produced yellow fever and malaria. (In fact, the name "malaria" comes from the Italian mala aria, which means "harmful air.")

Even men of science became locked in fierce disagreement. Debate raged between those who believed that these pestilences were communicable diseases caused by some infectious agent and spread by materials contaminated by patients, and those who clung passionately to the idea that they were air- or waterborne.

These differences in opinion gave rise to wildly different approaches to prevention and treatment. For instance, during a yellow fever epidemic in Philadelphia in 1793, Dr. Benjamin Rush, a well-known professor and physician, attempted to cure his patients by bleeding them to get rid of the environmental contaminants that he believed had invaded their bodies. Around the same time, in Washington, D.C., Dr. Albert King hypothesized that mosquitos were the real culprits, but he became the object of much ridicule when he proposed that a gigantic mesh screen be erected around the U.S. capital to keep the insects out. Another hundred years would pass before scientists realized that King was on the right track.

In 1880, as de Lesseps was en route to Panama to begin work on the canal, Dr. Charles Alphonse Laveran, a French physician working in the then-French territory of Algeria, discovered Plasmodium, the organism that causes malaria, in the blood of a patient. The news came too late for de Lesseps. On the other hand, it might not have mattered: de Lesseps did not believe in the mosquito theory. He believed in miasmas.

The next year, a Cuban physician, Dr. Carlos Finlay, made a discovery that would revolutionize disease control and ultimately make possible the construction of the Panama Canal. He identified the Aedes aegypti mosquito as the carrier of yellow fever.

Finlay’s breakthrough had glitches, however. He correctly had surmised that the mosquito was spreading the disease by biting people previously infected with the disease and then transmitting the disease agent to other people through its bite. But when he attempted to prove his theory by having infected mosquitos inoculate healthy volunteers with the disease, he failed. What Finlay didn’t know was that the virus needed to incubate for approximately 12 days inside the insect in order to develop. He was attempting to inoculate his volunteers with the virus using mosquitos that had only been infected a few hours. More years would pass before these missing pieces were added to complete the puzzle.

Finlay continued his quest to identify the agent causing yellow fever and reveal how the mosquito transmitted it. At the same time, building on the work of Sir Ronald Ross, a British physician and Nobel laureate (1902) who identified a malaria plasmodium in the stomach of an Anopheles mosquito like the one Laveran had found in human blood, Finlay formulated a detailed plan for combatting both yellow fever and malaria.

In 1898, the United States battleship Maine blew up in Havana’s harbor. The U.S., already at odds with Spain over its harsh colonial policies in Cuba, declared war. During the hostilities, it soon became apparent to the U.S. military that yellow fever was claiming more lives than the actual war itself. In response, the government dispatched a medical commission, whose members included Dr. Walter Reed, to find a way of halting the epidemic. Under the leadership of Dr. William C. Gorgas, the commission mounted a vigorous campaign to rout the disease, but since neither Gorgas nor Reed put much stock in Finlay’s mosquito theory, efforts focused initially on ridding the Cuban capital of the filth and contamination presumed to cause the disease. But when the yellow fever death toll rose despite a massive cleanup effort, Reed decided to test Finlay’s theory.

Reed constructed two small buildings through which air could circulate freely (to first show that the disease was not airborne). In one building he had volunteers sleep for 20 nights in the foul bedsheets and garments of yellow fever patients. In the other building, volunteers slept next to infected mosquitos, but were separated by screens. In this experiment, Reed did not use recently infected mosquitos like Finlay had, but rather insects that had been infected for some time. Then one volunteer was exposed to infected mosquitos for three successive nights. This volunteer was the only one to develop yellow fever.

Proof at last was conclusive: Aedes aegypti was the culprit. Reed had yielded the knowledge that would free Havana from yellow fever.

Despite this proof, many in the medical community--including Gorgas--remained unconvinced of Finlay’s theory. Nevertheless, at the direction of the Military Governor of Cuba, Gorgas and his team set about eliminating the mosquito and its breeding places. All yellow fever patients were quarantined to prevent them from infecting remaining mosquitos.

The results were spectacular. Within less than a year, yellow fever had been virtually eradicated. This triumph was all the more remarkable in that Gorgas managed to secure the collaboration of the Cuban people--no small feat, since yellow fever posed no real threat to the majority of Cubans, most of whom had contracted mild cases in infancy, which rendered them immune to subsequent attacks. It was the unprotected, non-immune foreign troops who were dying of the disease.

Gorgas then proceeded to destroy Anopheles habitat and scored similarly dramatic success against malaria. The Havana anti-mosquito campaigns--the first large-scale systematic public health effort of its kind anywhere in the world--not only provided a formula for controlling epidemics elsewhere, they served as an early model for effective health promotion and community involvement.

Everything that had been learned in Cuba would now be brought to bear in cleaning up the area of the future Panama Canal.

But not before certain political issues were resolved. At the time, Panama still belonged to Colombia. A bitter civil war ensued from 1900 until 1903, when--with U.S. support--it finally won its independence.

Meanwhile, a second French company had bought the canal franchise in 1894, largely to keep the project alive. In 1904, they sold their holdings to the U.S. for $40 million. Plans to resume construction began. Taking stock of the huge numbers of workers the French had lost to malaria, yellow fever, and other ills related to Panama’s swampy environment, the newly formed Panama Canal Commission decided that the first step was to tackle the sanitary situation in the Canal Zone.

President Theodore Roosevelt sent a group of experts that included Gorgas, Reed, and others who had taken part in the Havana triumph. Since they knew now who the enemy was, they made plans to wage an all-out mosquito war.

Having faced scientific and political embroilments, Gorgas, as the canal’s chief sanitary officer, now ran up against an unwieldy bureaucracy. Writes David McCullough in his history of the Panama Canal, The Path Between the Seas: ". . . to hire a single handcart for an hour required six separate vouchers. Carpenters were forbidden to saw boards over 10 feet in length without a signed permit." To add to this, the canal commissioners remained skeptical about the mosquito theory, and dismissed Gorgas’ requests for supplies to kill the insects as nonsense.

In the meantime, a veritable health crisis was brewing. As hundreds of non-immune workers reached Panama, the number of yellow fever cases and deaths began to grow steadily, raising the specter of an uncontrolled epidemic. By June 1905, fear of the disease had grown so intense that three-quarters of the canal work force, including the chief engineer, had fled Panama. It appeared that, once again, Aedes aegypti would foil attempts to build a canal.

Faced with the prospect of failure, President Roosevelt fired all the commissioners, appointed new ones, and named John F. Stevens the new chief engineer. Stevens believed in Gorgas and gave him free reign. Without the bureaucracy, Gorgas was able to do what needed to be done to free the isthmus of yellow fever--get rid of the mosquitos.

He and his colleagues began by eliminating Aedes aegypti breeding places. In the process, such places as Panama City, Colón, Cristóbal, Ancón, La Boca, and Culebra received piped water service, thus dispensing with the centuries-old need to rely on rain barrels and other fresh-water receptacles in which the mosquito might deposit its eggs.

At the same time, they carried out a sweeping fumigation campaign. In Havana, which had 200,000 inhabitants, only the houses of yellow fever patients and neighboring houses had been fumigated. Panama City, which had only 20,000 inhabitants, and Colón, which had a much smaller population, were fumigated house by house. For the first time in the history of the isthmus, yellow fever was stamped out. This was a major victory. Yet it was eclipsed by an even bigger threat that remained: Panama’s most serious problem was malaria, which most believed to have killed even more people than yellow fever.

The two diseases differed in several ways. Yellow fever confers immunity, but malaria does not. Repeated attacks are frequent, and people who have been infected remain capable--for years--of transmitting the disease to others through the bite of an anopheline mosquito. Gorgas estimated that most of the 12,000 people living along the Canal Zone carried the infection.

The mosquito carriers also had very different habits. Whereas the Aedes aegypti lays its eggs in fresh, still water, Anopheles breeds in swamps. And Panama had thousands of swamps.

So Gorgas and his team turned to investigating the habits of Anopheles. Research showed that the mosquito could fly only short distances, so Gorgas ordered the drainage or destruction of all potential breeding places located close to human dwellings. Anopheline eggs and larvae were eliminated by introducing fish that ate them or by cultivating water plants that blocked the sunlight they needed to develop. Doors and windows were screened to keep the adult mosquitos out, and underbrush that might shelter them was cut. In addition, the antimalarial drug quinine was dispensed to all inhabitants as a preventive measure.

The results were nothing less than spectacular. The number of malaria deaths fell to zero, and the number of cases among canal workers also dropped dramatically. The isthmus had been freed from the grip of yellow fever and malaria. At last, the canal could be completed.

More importantly, one of the world’s most infamous pestholes had been transformed into what Gorgas would later call "the garden spot of the world." Many of the health gains made in the canal construction era have endured to this day. Moreover, the yellow fever and malaria campaigns carried out in Panama provided a working blueprint for the control of these diseases that was subsequently applied around the world.

Thus, August 15, 1914, the date on which the Panama Canal was inaugurated, marked not only a colossal achievement in hydraulic engineering, but also ushered in a new era of improved international health, communication, transportation, trade, and commerce--in large part due to the invaluable public health contributions of men like Laveran, Ross, Finlay, Gorgas, and Reed.

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Harry Castro Stanziola is a medical doctor and columnist for the Panamanian newspaper La Prensa