During the Vietnam War, the Chinese army endured an overwhelming wave of firepower from the United States and South Vietnamese military.  Landmines threatened every trodden step, artillery fire and airstrikes thundered from above, and sniper fire flashed without warning.  The Chinese army grew exhausted and exasperated during this onslaught.  However a much greater, invisible danger lurked during the night.  Far worse than the possibility of being picked off by sniper fire or blasted by artillery shells was the possibility of being bitten by the indiscernible mosquito.  The Chinese soldiers were ravaged by mosquitoes carrying malaria.  They watched as their brothers fell into everlasting comas and violently convulsed from seizures.  Soon the silent disease claimed even more lives than military combat.

Today, malaria remains one of humanity’s greatest scourges.  As of 2015, over half of the world’s population was at risk of malaria. With over 200 million cases that year, nearly half a million people perished at the hands of this disease (#).  Malaria begins when an infected female Anopheles mosquito feeds on human blood and transmits parasites of the genus plasmodium to the human host. Ten days later, mild symptoms begin to appear: a mere fever, headache, and chills.  If not treated within twenty-four hours from the onset of symptoms, the disease can rapidly progress to severe illness and death.  Malaria parasites have evolved over tens of thousands of years to become unscrupulous killers of mankind.

Malaria plagued Chinese troops during the Vietnam War.  Prompted by Vietnamese and Chinese leaders, Mao Zedong launched the secret Project 523, named after the date it began, May 23, 1967 (#).  The project quietly organized 500 scientists to search for an effective treatment to malaria.  The Chinese scientist Tu YouYou emerged as a leader for the group studying ancient Chinese herbal medicines.  Under her leadership, the team painstakingly pored over ancient texts, investigating thousands of herbal preparations.  They made hundreds of extracts from herbs and tested these treatments in mice and monkeys.  One in particular, artemisinin, showed promise.  Named 青蒿素 (qing hao su) in Chinese, artemisinin is an extract of an herb native to China called sweet wormwood.  Artemisinin was used by ancient Chinese herbalists over two millennia ago to treat malaria.  When the drug was tested, the disease was miraculously cured in animal tests.  When the time came to test in humans, Tu YouYou felt a selfless responsibility as the leader of her research group and thus she offered herself as the first human subject.  After the treatment was evaluated and deemed effective for treating malaria, the group’s results were anonymously published in 1977 (#).  Amidst the violent upheavals of the Vietnam War, a weapon was found by Tu YouYou to combat humanity’s microscopic nemesis.  The weapon was artemisinin.

Artemisinin was met with skepticism by the broader scientific community.  It was a large and unwieldy chemical compound, surely too unstable as a drug.  And the scientific community has long rebuked the seemingly absurd promises of Eastern medicine.  But upon closer evaluation and experimentation, it became clear that artemisinin was an effective candidate for fighting malaria.  At the same time, malaria parasites were developing striking immunities to existing treatments such as chloroquine and sulfacoxine.  As a result the World Health Organization swiftly endorsed an artemisinin-based therapy as its choice of treatment against malaria.

After artemisinin is taken by a patient, parasite biomass and malaria symptoms rapidly diminish within hours.  But despite its impressive effectiveness, artemisinin’s mechanism of action has continued to evade scientists (#).  Scientists continue to disagree on the molecular target of the drug.  Our lack of understanding of the drug’s mechanisms has severely hindered our ability to produce novel anti-malaria drugs.  Nevertheless, artemisinin definitely works.  Life endures over the deathly grip of malaria.

Today, artemisinin-based combination therapies (ACT) are still recommended by WHO as one of the first-line treatments for malaria (#).  “In ACT, artemisinin is used with a long lasting anti-malaria drug because of its short half-life,” says Dr. Bill Moss, an epidemiology professor working at the Johns Hopkins Malaria Research Initiative (#). “In combination,” he says, “ACT drugs are highly effective in clearing parasites and treating patients.”  Moss has studied the epidemiology and control of malaria in southern and central Africa.  His work has spanned Zambia, Zimbabwe, and the Democratic Republic of Congo.  While ACT is used to treat malaria, there have also been successful prevention measures against malaria such as insecticide-treated bed nets and indoor insecticide spraying.  Recently, however, mosquito vectors have begun showing increased resistance to insecticides.  Additionally, malaria parasites have begun showing resistance to artemisinin, particularly in Southeast Asia.  “Extensive efforts are underway to eliminate resistant parasites,” Moss continues, “The spread or emergence of these parasites in sub-Saharan Africa would be a public health disaster.  The big hope is that one day a highly effective vaccine will be developed, [but] this goal has been elusive over the past few decades.”  Current efforts against malaria have primarily included scaling up current efforts such as ACT and developing novel interventions.

One such endeavor has brought modern biotechnology to the fight against malaria.  Dr. Jay Keasling, a chemical engineering professor at Berkeley, reengineers metabolic pathways within microorganisms to produce resources valuable to humans such as biofuels and drugs.  In 2003, Keasling and his group discovered an ingenious way to aid in the fight against malaria (#).  They successfully implanted the genes of sweet wormwood, the artemisinin-producing plant, into yeast cells.  This transformed yeast into churning cellular factories that produced synthetic artemisinin.  A key disadvantage of the drug is the fact that it is a plant extract.  This makes the quality, supply, and cost of the drug unpredictable, heavily dependent on the crop’s success in a particular year.  Keasling’s solution provides a cheap and reliable alternative to agricultural production of artemisinin.  Building upon their initial discovery, his group has hurdled forward to ensure that artemisinin is available to those afflicted by malaria.  With over $50 million in support from the Bill and Melinda Gates Foundation, Keasling has teamed up with French pharmaceutical company Sanofi to launch large-scale production of the drug using his technology (#).  As a result of this partnership between academia and industry, millions of ACT treatments have already been shipped across Africa.

Keasling’s work re-engineering micro-organisms to produce artemisinin has merged cutting-edge biotechnology and millennia-old Chinese medicines.  It showcases how both the past and the future have enormous potential to influence the present state of health care.

Due to the work of a multitude of individuals, from Tu YouYou to Keasling, society has taken tremendous steps towards treating and perhaps one day eradicating malaria.  Over the last 15 years, over half of the 100 plus countries with ongoing malaria transmission achieved an at least 75% reduction in new malaria cases (#).  And according to WHO, 16 countries reported zero indigenous cases of the disease.  This progress has largely been a result of ACT and the two primary forms of vector control, insecticide treated bed nets and indoor insecticide spraying.  Nevertheless substantial progress remains to be made in areas bearing the highest burden of malaria, primarily sub-Saharan Africa and southeastern Asia.

In 2015, Tu YouYou stepped onto stage in Stockholm, Sweden.  A discordant crowd filled the hall: older Europeans dressed in formal attire intently listened while a younger Chinese audience pointed their phone cameras towards the stage.  At 84 years old, Tu YouYou had been awarded the 2015 Nobel Prize in Physiology and Medicine (#).  She was idolized in China as the first Chinese scientist and Chinese woman to win the prize.  As Tu YouYou began her Nobel lecture, an official knelt beside her in deference and held up a microphone for her to speak.  Looking down at her notes, she spoke in slow and deliberate Mandarin while English words were sprawled across the projector’s screen.  Within the hall, a story unfolded of her tireless search for a treatment against malaria.  It was a story of selflessness, hope, and vision.  The rediscovery of artemisinin showed that there may be much to learn from the ancient and natural worlds– that the treasures of our past may yet yield the miracles of tomorrow.

Posted by Daniel Huang

Daniel is a sophomore studying Biomedical Engineering at the Johns Hopkins University. As a managing editor, Daniel leads writing and editorial efforts within the clinical medicines group. Daniel is involved in the Ha Lab, where he repurposes nanopore platforms to study biophysical phenomenon at the single-molecule level. In addition, he is involved in BME Design Team, pro-bono consulting projects, and the Taiwanese-American Students Association. He is interested in health care entrepreneurship and consulting.

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