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Public health: The malaria wars

Robert Seder applauds the chronicle of a secret US wartime project to vanquish the disease.

The Malaria Project: The U.S. Government's Secret Mission to Find a Miracle Cure

New American Library: 2014. 9780451467324 | ISBN: 978-0-4514-6732-4

Malaria has a long history and a deadly present: every year it kills as many as 1 million people, mostly children in sub-Saharan Africa. Over the past decade, mortality from the disease — caused by the Plasmodium parasite transmitted by mosquitoes — has been cut through the use of bed nets and other public-health measures championed by the World Health Organization's Roll Back Malaria campaign, among others.

The effectiveness of such measures may have plateaued, however, and the disease is becoming resistant to drugs such as artemisinin-based therapies. In 2015, the first vaccine (GlaxoSmithKline's RTS,S) will be considered for approval in Africa. It confers 30–50% protection that wanes over time. Given all that, insights into historical grapplings with the disease are highly useful.

During the Second World War, malaria control and prevention was a big problem for the US military. Credit: Bettmann/Corbis

Such insights abound in The Malaria Project, science journalist Karen Masterson's chronicle of a secret Second World War scheme run by the White House and US War Department. In the 1940s, the project drew in leading scientists and clinicians to find a cure for malaria — at the time decimating US troops — and isolated the safe, effective drug chloroquine. As Masterson shows, today's fight against the disease, heavily weighted towards drug and vaccine development, bears the project's stamp.

Masterson discovered the project in 2004 in a letter in the US National Archives. Writing in 1943, physician George Carden described a plan to test malaria drugs on patients at a psychiatric hospital in Boston, Massachusetts. Carden was part of the Malaria Project, working with chemists, entomologists, immunologists and clinicians to assess some 14,000 malaria-drug candidates.

Masterson relates how scientific understanding of malaria advanced. The project's trailblazing tropical-disease specialist Lowell Coggeshall, for instance, had worked on mosquito control in canal and dam construction since the 1920s. His observations, such as that a cure does not prevent reinfection, remain pertinent. But it was Swedish renal specialist Alf Alving who pinned chloroquine down.

Malaria could not be grown in culture, so the drugs were tested in human volunteers, including conscientious objectors and medical students. The approach was modelled on 1917 research by Julius Wagner-Jauregg. The Austrian psychiatrist discovered that some people with advanced syphilis (who would otherwise have died) could be cured if they received blood taken from people infected with malaria.

In the Malaria Project's crucial studies, at Stateville Prison in Illinois, Alving recruited prisoners to act as both assistants and test subjects for compounds that were safe and protective in animal tests. He lobbied for inmates who tested the drugs to get higher compensation and certificates of merit for use at parole hearings, and helped them to get jobs after release. One of Alving's assistants was the infamous murderer Nathan Leopold.

Alving's breakthrough came from studying SN-7618, a compound that could be given once a week with minimal toxicity. Ironically, the original version, sontochin, was made in Nazi-occupied Paris and conveyed to the US military by Vichy medics. Alving found that changing the dosage and intervals at which it was given would cure malaria, and chloroquine became the standard treatment until resistance developed in certain strains. Human volunteers still test malaria vaccines because such safe, effective drugs can cure them of the controlled infection.

A revelation of The Malaria Project is the toll malaria took on troops: some half a million US soldiers were infected during the Second World War, for instance. Douglas MacArthur, leading Allied forces against Japan, realized that malaria was weakening troops and launched control operations. Leading troops in Italy, by contrast, George Patton showed little compassion for infected soldiers and did not act — even as Adolf Hitler flooded land to encourage mosquito breeding.

The Malaria Project also covers the key role of the US Rockefeller Foundation and Rockefeller Institute for Medical Research (now Rockefeller University). Rather than search for magic bullets, they focused on malaria eradication through public health and cost-effectiveness. Today, the Bill & Melinda Gates Foundation (from which I receive some funding) plans to use public-health measures as well as drugs and possibly vaccines in its malaria eradication strategy.

Mosquito control, improved education and economic development remain central. But more than 60 years after Alving's breakthrough, the most crucial advances will come from safe, effective and durable vaccines to prevent malaria, and drug treatments to eradicate it.

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Seder, R. Public health: The malaria wars. Nature 514, 166 (2014). https://doi.org/10.1038/514166a

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