Probably everyone heard the legend of the “Flying Dutchman” - the famous ghost ship. They wrote about him in books, sang in songs, made films and wrote pictures. Someone believes in its existence, someone does not. There are different versions of its origin: from fatal love to a terrible curse. But there is one version that makes the legend of the “Flying Dutchman” quite real.
In the 17th century, ships with a yellow flag began to arrive in English ports. "Yellow Jack" - so called it the sailors, by analogy with the maritime flag of the British Empire - "Union Jack". It was a quarantine flag, which was raised before entering the port if there were patients with fever aboard. At that time, the population of Central America and the Caribbean islands suffered from severe, recurring epidemics, and it was then that the British doctors on Barbados suggested calling the unknown disease yellow fever because of the characteristic jaundice that develops in the majority of cases.
It is curious that the Republic of Haiti owes its existence to yellow fever. In 1801, the island of Haiti laid siege to the 25,000-strong army of Napoleon in order to suppress the uprising. However, Yellow Jack struck at the French with extraordinary strength, and an easy, it seemed, victory turned into a defeat for Napoleon. 22 thousand soldiers and officers were killed, and the survivors only had enough strength to evacuate artillery and horses from the island. In 1804, Haiti proclaimed itself an independent republic.
It is believed that the pathogen initially circulated among the population of West Africa, which, having been ill in childhood in a mild form, had a lifelong immunity, was not exposed to major outbreaks. However, with the beginning of the active slave trade, the disease spread throughout the world, where there was no immune layer (on their ships, the slave traders also brought specific vectors - Aedes aegypti mosquitoes).
In 1895, an armed uprising began in Cuba, and most of the island was liberated from the Spaniards. Having decided to take advantage of the situation, the United States landed its troops in Cuba, unleashing a war against Spain. But soon they had to wage war against Yellow Jack, because losses from the fever claimed more lives than the bullets of the Spaniards. In 1900, the American command sent a special commission to Havana to study the causes of the spread of yellow fever. The head of the commission, Major V. Reed, a military doctor, D. Carroll, a surgeon, an entomologist, D. Leizer, and A. Agramonte, a Cuban pathologist, conducted a brilliant epidemiological investigation at that time.
The Commission began work in the midst of the July heat, but the first attempts to detect the pathogen failed. It was also not possible to select animals susceptible to this disease. Then the members of the commission decided to conduct experiments on themselves. Assuming that the mosquitoes can be carriers of a contagious beginning, they raised a group of insects from the eggs that never ate blood, fed them with the blood of the sick, and then with their own.
The first experience put on himself D. Carrol.Having fallen ill, he proved that mosquitoes are the carrier of the fever. Although Carroll’s illness was severe, he still recovered. Leizer, who was bitten while collecting infected mosquitoes in a ward with seriously ill patients, fell ill and soon died, marking the beginning of a long list of researchers who died while studying yellow fever.
Then Reid, hiring volunteers from the local population for money, conducts a series of experiments on them, infecting them through mosquito bites, and Carroll passes patients' blood through filters with very small pores through which bacteria do not pass. With the resulting filtrate, it infects three volunteers, and two of them develop yellow fever. In the report, Reed first writes that the causative agent of yellow fever is a filterable virus. After receiving these data, the Chief Sanitary Inspector of Havana, V. Gorgas, began the total destruction of mosquitoes, filling all possible breeding sites with kerosene. The measures taken by Gorgas proved to be very effective - after two years not a single case of the disease was detected.
He successfully applied his experience later in the construction of the grandiose Panama Canal, which was to connect two oceans.When several tens of thousands of graves crowned the first stage of construction, the United States invited Gorgas, who, using his methods of fighting mosquitoes, was again able to stop the epidemic.
But the fight with Yellow Jack has just begun. Although D. Carrol determined that yellow fever is caused by a virus, he could not isolate the pathogen itself. In 1901, two expeditions set off almost at the same time to find him. In the West Africa, the British worked, and in South America - the expedition of the Rockefeller Institute from New York, led by Japanese microbiologist X. Nogushi, shortly before the famous discoverer of syphilis. Investigating the blood of patients, Nogushi found leptospira in one of the samples, and immediately published an article describing it, claiming that she was the causative agent of yellow fever. Unfortunately, the authority of Nogushi outweighed all the data of Reed's experiments, because he was just an ordinary army doctor, and he also died from appendicitis in 1902.
On the other side of the ocean, the British expedition adopts the method proposed by Nogushi. However, after examining hundreds of blood samples, they could not isolate leptospira.Upon learning of this, Nogushi comes to their aid, trying to prove the correctness of his conclusions, but he himself becomes infected in the laboratory and dies from yellow fever. After his death, a group of Englishmen managed to find out the reason for Nogushi’s delusion: in South America, where his expedition worked, a similar clinical disease, leptospirosis, spreading in rats, occurs. The error of Nogushi, sending research to several groups of scientists on the wrong path, delayed the release of yellow fever virus for a long time.
Considering the destruction of mosquitoes to be quite an effective measure to combat yellow fever, the Rockefeller Institute, having turned off the expedition, focused on improving these methods. However, soon a new fever broke out in Africa, the reservoir of which turned out to be monkeys, and the carrier was a completely different kind of mosquitoes. During logging operations, woodcutters were infected by mosquitoes, and when they arrived in the villages, they infected local mosquitoes.
This made the eradication of yellow fever with the help of sanitary measures almost unreal, because it is impossible to eliminate mosquitoes in thousands of forest areas, as it is impossible to limit the spread in the jungle of infection carried by flocks of infected monkeys.This prompted to resume the search for a pathogen to create a vaccine, because only with the help of mass immunization of the local population and all newcomers could we hope for a real victory over the yellow fever.
In 1927, the Rockefeller Institute sent a new expedition to Africa in search of the causative agent of yellow fever. She is joined by Professor of Pathology at the London Hospital A. Stokes. Having infected the rhesus monkeys with a filtrate from the blood of sick people, he finally gets the desired result: the animals get sick with a typical yellow fever. Having finally received the causative agent and laboratory animals susceptible to the virus, Stokes dies after contracting yellow fever ... Shortly thereafter, another member of the expedition, V. Young, infects himself and the local African technician with the blood of a sick person containing yellow fever virus to make sure that the role of immunity, which he does not have, but the laboratory technician has. Young died because he had no immunity against yellow fever.
In 1929, the tragic list of Yellow Jack's victims was supplemented by two more members of the expedition: microbiologist R. Lewis and entomologist T. Hein were killed.
In the same year M.Findlay received the first experimental vaccine from formalinized liver and spleen of monkeys with yellow fever. Having introduced it to healthy monkeys, they found antibodies against the virus in their blood. When the serum of their blood was introduced to new monkeys, and then they were infected with the yellow fever virus, they did not get sick. It was the first real success! Laboratory workers began to inject themselves into the blood serum of ill people to protect themselves in the event of infection.
But the serum protects only a few months, needed a vaccine that gives lasting immunity. And in 1937, the staff of the Pasteur Institute in France and Harvard University in the USA succeeded in creating two vaccine strains of equal value for their protective effectiveness: Dakar and Asibi.
During World War II, these vaccines were massively received by soldiers who fought Rommel on the African front. However, the French vaccine had a lot of side effects and was soon banned, and the developer of the American vaccine M. Taylor in 1951, the Nobel Committee awarded the prize in physiology and medicine.
The history of the study of yellow fever without too much pathos can be called an example of the heroic and selfless work of scientists.Fortunately, they died not in vain: having given the world a vaccine, they saved millions of lives from this deadly disease.