The Awards:
Over the years, four Nobel Prizes have been awarded for malaria-based work. The 1902, 1907, 1927, and 1948 Nobels in Physiology or Medicine have all gone to work that has improved our understanding of, or ability to combat malaria.
The Science:
Malaria has been with us for over 50,000 years. Identified in the autopsies of Egyptian mummies, written about in ancient China, and implicated as a major factor in the fall of Rome. Malaria most likely developed in Africa, but quickly spread from there with the help of travellers, explorers, and colonialists to almost every corner of the earth by the 19th century. Malaria has been with us for so long that it is considered one of the greatest modern selective pressures on our species.
Today malaria infects over 250 million people a year, killing about one million. Infants and the elderly in the developing world are at the greatest risk. We’ve come a long way in understanding malaria over the last 150 years, yet there is still no vaccine. Controlling its vector, the Anopheles mosquito, is proving to be much more difficult in the developing world than it has been for Europe and North America.
The mosquito can’t be blamed for malaria though. Anopheles is merely the carrier of the pathogenic Plasmodium, a single-celled eukaryotic organism that lives half its lifecycle in humans and the other half in mosquitoes. It was the recognition of Plasmodium infection as the cause of malaria that won Alphonse Laveran the Nobel Prize in 1907. Working at a military hospital in Algiers in 1880, Laveran discovered Plasmodium in the blood of a malaria victim. The Nobel Prize honoured this discovery and his other discovery that trypanosomes, another parasite, cause sleeping sickness.
The Plasmodium lifecycle begins in an infected human. An infected person’s blood carries the gametes (male and female sex cells) of the parasite. Once bitten by a mosquito, the gametes are sucked up as part of the blood meal and enter the mosquito’s gut. It is here that the two gametes come together to form the zygote. This phase of Plasmodium’s lifecycle can only happen in the mosquito.
The zygote buries itself into the mosquito gut lining, and after many cellular divisions develops into a sac of sporozoites. The sac eventually bursts, releasing the sporozoites that migrate from the gut lining to the mosquito’s salivary glands, where they wait for the bite that will land them into their next human host.
Many had hypothesized that malaria was linked to mosquitoes—the ancient Romans knew that dredging swamps (mosquito breeding grounds) reduced the incidence of malaria—but a definitive link had never been shown experimentally. In 1897, after dissecting an Anopheles mosquito (only genus Anopheles can carry Plasmodium) four days after it had fed on a malaria patient, Sir Ronald Ross found Plasmodium in its stomach, unequivocally linking it to Anopheles. Using birds as a model host (different strains of Plasmodium have different animal hosts), Ross also showed how Plasmodium migrates towards the Anopheles salivary glands to transmit malaria between birds. His work was awarded a Nobel in 1902.
Once the Plasmodium sporozoites reach the bloodstream of their new host, they can colonize the liver or a red blood cell (RBC). Those that enter the liver cells stay there for only a short time, rapidly replicating themselves until the infected cell bursts, releasing Plasmodium cells into the blood where they can enter an RBC.
Plasmodium is clever at evading the host animal’s immune system: it is protected from the immune cells of the bloodstream inside a RBC. It also causes the colonized RBC to behave differently. Instead of circulating throughout the body, Plasmodium species make the RBC sticky, so that the RBC will cling to the sides of blood vessels safe from the spleen’s “cleaning” action. Even when free in the bloodstream, Plasmodium is resistant to the immune system because it has the ability to “scramble” the proteins on its surface of the cell into myriad “disguises” that the immune system cannot keep up with. Gaining a natural immunity to Plasmodium is virtually impossible as a result.
Once infected, a patient can go through cycles of coldness and fever. They may exhibit anemia (the RBCs are occasionally broken open by Plasmodium searching for a new host RBC, releasing hemoglobin and iron), vomiting, joint pain, and kidney or liver failure, which unless treated may result in death. In a child (whose brain is still developing), the severe anemia associated with malaria can result in brain damage.
Treatment of malaria is managed by a number of anti-malarial drugs that are readily available in the developed world, but often are out of reach for patients in developing countries. Timely treatment can assure a complete recovery. Traditionally, malaria was treated with quinine—discovered by the people of Peru in the bark of the cinchona tree and brought to Europe by the Jesuits—which works by blocking Plasmodium’s ability to reproduce itself in the blood, giving the body the chance to fight it off.
Surprisingly, malaria hasn’t always been fought off; it has also been used as a therapeutic. Before the advent of antibiotics, Julius Wagner-Juaregg developed a method of treating cerebral syphilis (caused by a sexually transmitted bacterial infection) by inducing a fever with malaria. Some patients with advanced neurosyphilis could spontaneously be cured—supposedly the induced fever helped fight the syphilis bacterium—and then the malaria could be treated with quinine. Not every patient showed full recovery, but many patients saw relief of their symptoms (mania, dementia, depression). For this discovery, Julius Wagner-Jauregg won the 1927 Nobel Prize in Physiology or Medicine. Penicillin, however, made this treatment obsolete.
The best way to prevent contracting malaria is to avoid infested areas, and the best way to bring down infection rates is to control the Anopheles mosquito population through improved sanitation, draining or paraffin-coating the wetlands that are the breeding ground for Anopheles, or the application of pesticides.
Historically, the most effective pesticide against Anopheles has been DDT, a contact poison that won Paul Hermann Müller a Nobel in 1948. DDT had been previously synthesized by a Viennese pharmacist, but Müller resynthesized DDT and tested it for pesticide activity. He soon found that it was a powerful agent against arthropods, including Anopheles, killing them merely by contact. In the 1940s, DDT was literally painted onto the interior walls of houses to prevent the spread of typhus (its carrier is the body louse) and malaria.
DDT, in combination with other measures, effectively eliminated malaria from most of the developed world in the 1950s and ’60s, but its use became progressively less effective with the rise of DDT-resistant mosquitoes. Eradication has not been as successful in the developing world, especially Africa, where other political and cultural factors have played a role in stymieing eradication.
DDT has its dark side too. It is the poster-child for the ills of biomagnification—the process of “magnifying” the concentration of a chemical as it goes up a food chain—becoming very toxic in larger organisms. One of DDT’s greatest assets and liabilities is its lasting power, which means that it remains in the environment, and within the animals that ingest it, decades after its application. Its use against malaria is only the tip of the iceberg; DDT was overused for years as an agricultural pesticide and accumulated in significant quantities in our environment. The accumulated DDT is to blame for the eggshell thinning of many now-endangered birds, such as the bald eagle, and is a suspected carcinogen. Even though the use of DDT is now strictly controlled and banned in most countries, it is still used to manage malaria in some parts of the world.
The Significance:
Malaria is now a disease affecting the very poor and the poorest nations. Not only is it a symptom of poverty, but it also causes poverty by keeping young, healthy people from being productive. Malaria was eradicated by the 1960s in affected Western nations, but still plagues much of Africa, South Asia, and South America. The Bill and Melinda Gates Foundation, which sponsors research and many community programs, has set 2015 as the date for the global eradication of malaria.
Climate change (warmer temperatures and rainfall changes) are slowly affecting the boundaries of Plasmodium-hospitable regions. This is already resulting in the spread of malaria to regions that have either never dealt with malaria, or haven’t had to for decades. This may soon pose a global health risk.
Today most efforts to quell malaria are aimed at education and personal protection. This includes taking anti-malarial drugs before travelling to an affected area, using a pesticide embedded bed-net for sleeping, and sporadic preventative treatment of infants with anti-malarial drugs.
