A Short (Hi)story of Malaria: Darkness and Light (Part 3)

[This post has been written by Xavier Fernàndez-Busquets and it is the third and last post on a series of the history of malaria]

The contemporary history of malaria was ushered in with a drift to the limits of ethical behavior

The contemporary history of malaria was ushered in with a drift to the limits of ethical behavior. In 1927 Julius Wagner-Jauregg was awarded the Nobel Prize in Physiology or Medicine "for his discovery of the therapeutic value of malaria inoculation in the treatment of dementia paralytica." Euphemistically called malariotherapy, this practice consisted of the treatment of disease (mainly neurosyphilis) by raising the body temperature through infecting the patient with malaria. Although this might seem a thing of times long gone, malariotherapy was still being advocated as a treatment for HIV patients in a 1997 paper by Henry Judah Heimlich, best known for his invention of the Heimlich maneuver which has saved so many lives of people choking because of an olive stone lodged in the throat.

Sadly, the chemical war on malaria of the 20th century was not initiated by an altruistic motivation spurred by the millions of people dying in Africa. The developed nations began investing huge amounts of money to find a cure only when the disease started killing scores of soldiers in the WWI battlefields. Paul Ehrlich (1854-1915) coined the term Magic Bullet to define a hypothetical drug able to kill pathogens without affecting healthy host cells. He developed Methylene Blue, the first synthetic antimalarial of widespread use in the war front, which nevertheless was never liked by the troops because it stained blue the eye’s sclera and also the urine.

The full chemical arsenal against malaria was not launched in earnest until WWII

But the full chemical arsenal against malaria was not launched in earnest until WWII. By that time, the alkaloid quinine was the most efficient antimalarial by far (and an ingredient in the tonic water that you have in the fridge today). However, its side effects and the difficulties in obtaining it from its natural source, the cinchona tree growing scattered in the depths of South American rainforests, stimulated the search for a synthetic analog. Germany and the Allies developed literally hundreds of quinine derivatives, substituting or modifying virtually every single atom in the molecule. The result of that chemical race was chloroquine, a potent antimalarial with almost no side effects thought at the moment to be the Magic Bullet imagined by Ehrlich and capable of eradicating malaria. Unfortunately, it was not to be, and a few years after its deployment resistance began to evolve in the parasite, which has rendered this once wonder drug essentially useless in many endemic areas.

Somewhat surprisingly, the chemical warfare against malaria found its most lethal weapon not acting against the parasite, but against the mosquito vector. Dichlorodiphenyltrichloroethane (aka DDT) is a colorless, tasteless, and almost odorless crystalline organochlorine first synthesized in 1874. DDT's insecticidal action was discovered in 1939 by the Swiss chemist Paul Hermann Müller, to whom the Nobel Prize in Physiology or Medicine was awarded in 1948 "for his discovery of the high efficiency of DDT as a contact poison against several arthropods". The glory days of DDT, alas, abruptly closed in 1962 with the publication by Rachel Carson of Silent Spring, an iconic book for the environmentalist movement where the toxic effects of DDT were unveiled, ending up with it on the shelves of cursed chemicals where it has remained to this day, although many call for its reintroduction.

When WWII was at the top of its rage, the history of malaria enters its darkest time

When WWII was at the top of its rage, the history of malaria enters its darkest time. In the Nazi Germany, the SS Reichsführer Heinrich Himmler sent Klaus Schilling to work at the Dachau concentration camp. In 1946, during the Nuremberg trials the following statement could be heard: “My name is Professor Dr. Klaus Schilling. I have already worked on tropical diseases for 45 years. I came to the experimental station in Dachau in February 1942. I judge that I inoculated between 900 and 1,000 prisoners. These were mostly inoculated for protection. These people, however, were not volunteers.” But this medical misconduct was not exclusive of the Axis. At the Stateville Correctional Center, a maximum security state prison near Chicago, prisoners were also being used for testing antimalarial drugs. At the same Nuremberg medical trial, defense attorneys argued that, ethically, there was no difference between research conducted in American prisons and the experiments that took place in Nazi concentration camps. The malaria study was specifically mentioned.

Luckily, though, our short (Hi)story of malaria will end up with a shining bright chapter

Luckily, though, our short (Hi)story of malaria will end up with a shining bright chapter. In 2015, half of the Nobel Prize in Physiology or Medicine was awarded to Youyou Tu "for her discoveries concerning a novel therapy against malaria". Tu, the first Chinese woman to be a Nobel laureate, is known as the Professor of Three Noes: No postgraduate degree, No experience abroad, Not a member of any Chinese academy. She carried her work in the 1960s and 70s during China’s Cultural Revolution, when scientists (intellectuals) were denigrated as one of the nine black categories in society. In 1967 Mao Zedong responded to the call for help of Ho Chi Minh, who was in trouble because his army was losing the Vietnam war not against Uncle Sam but against malaria.

Mao launched Project 523 with the objective of finding a cure for the disease. Tu looked in the 340 A.D. Chinese classical medicine book Zhou Hou Bei Ji Fang (Handy Therapies for Emergencies), by Ge Hong, and dug out a recipe on how to prepare a remedy for periodic fevers. The method counseled to extract the active principle (actually artemisinin) by brewing leaves of Artemisia annua (Quinghao or wild Hao in Chinese) in temperate, not hot, water. And now here comes the most moving part of this little tale. Do you know where the name her parents bestowed on Prof. Tu comes from? It’s from an ancient Chinese saying: “Deer bleat “youyou” while they are eating the wild Hao."

To be continued.

More information

Read the part 1: A Short (Hi)story of Malaria: From Dinosaurs to a Simple "Bad Air"

Read the part 2: A Short (Hi)story of Malaria: The Discoveries that Brought Us Here