Raising the deadly

The planet’s deadliest animal is smaller than a paper clip, weighs in at around 2 milligrams, and has a dizzying top speed of 2.4 kilometers per hour.

They may be miniscule but mosquitoes wreak devastation across large swathes of the world. As a vector for diseases such as malaria, dengue fever, yellow fever and encephalitis, these blood-suckers infect millions each year. According to the latest figures, malaria alone claimed the lives of around 584,000 people in 2013, with close to 200 million cases of the disease.

Diyah Sudirman Made Ali raises mosquitoes for drug discovery research.

“When people learn what I do for a living they tend to think I’m crazy,” says Sudirman Made Ali. “But I am just like any other scientist fascinated by their field of research: mine just happens to be mosquitoes.”For most of us, being trapped in a hot, humid room with thousands of these tiny but lethal, winged tormentors is the stuff of nightmares. But not for one woman. Diyah Sudirman Made Ali—nicknamed Mosquito Mom by her colleagues—has made the study of mosquitoes her life’s work, and spends her days rearing a colony of thousands of Anopheles and Aedes mosquitoes at the Novartis Institute for Tropical Diseases (NITD) insectary in Singapore.

“The more time I spend observing the mosquitoes, understanding their needs, nurturing them and talking to them, the more fascinating they become,” says Sudirman Made Ali. “Actually, maybe I shouldn’t admit to talking to them. That does sound a little crazy!”Sudirman Made Ali is passionate about uncovering these insects’ secrets to advance drug discovery research. The ultimate goal is to find treatments for devastating diseases. To do this, she focuses on understanding the carriers.

NITD opened its insectary in Singapore in August 2013, making Novartis one of the first pharmaceutical companies to have such a facility in-house. Research at NITD supports the broader effort of the Novartis Malaria Initiative, which is working toward eradication of the disease. The insectary allows researchers to cultivate the very parasites that cause so much devastation. Take Plasmodium, the microbe responsible for malaria.

Under the right conditions, the Plasmodium parasite reproduces exponentially in Anopheles mosquitoes. Scientists can extract the microbe and inject it into human cells or animals to generate disease models, which aid teams researching treatments. They can use the models to test compounds and determine which ones prevent Plasmodia from multiplying and spreading, even among human liver cells. Existing malaria treatments are generally ineffective against the liver stage of the disease.

Growing a colony of mosquitoes isn’t easy. The insects are highly sensitive to changes in humidity, temperature, food sources and feeding times. In order for each species to thrive and reproduce, the conditions of its natural habitat must be recreated in the laboratory.

In addition to catering to the needs of Anopheles mosquitoes, Sudirman Made Ali nurtures Aedes mosquitoes, the principal vector for dengue viruses. Before she arrived, the insectary team struggled with a high mosquito mortality rate. They also had trouble getting the eggs to develop into adults.

“When Diyah joined us last year, her expertise and passion were transformative,” says Liting Lim, chief investigator at the insectary. “We now have a thriving colony of around 5,000 adults per generation.”

Mosquitoes feast on a cotton ball soaked with a sucrose solution. The mosquitoes resting on the blue base are full. Photo by Sandra Schluechter/Novartis

Sudirman Made Ali’s first task each morning is to check the larvae, feed them her formulation of fish food and protein from green bean powder, and count the success rate for each molt in the four larvae stages of the mosquito life cycle. She selects any larvae that have become pupa and moves them to a cage to prepare for the adult stage. Then it is time to check on the adult colonies, change the sugar solution they feed on and separate out any engorged mosquitoes as they prepare to lay eggs. Next, she feeds the mosquitoes their infected blood meals and ensures that they’re full—but not too full—of parasites. (As the parasite load increases, a mosquito’s fertility decreases.)

What about safety worries? Working with the planet’s deadliest animals cannot be without risks.

“The very first time you put your hand into a cage of mosquitoes, it does make your stomach flip,” says Sudirman Made Ali. “But we have stringent operating procedures in place, and we’re experts in working with mosquitoes. Safety issues are very well managed.”

Is there anything she doesn’t like about her work?

“I can’t lie,” she says. “Counting thousands of larvae day in, day out can get a little boring. But whenever I tire, I remember the excitement I felt when we first looked under a microscope at a mosquito that had been given an infected blood meal and saw parasites in the mid-gut. All the counting and checking are essential to produce the malaria parasites that we need for our drug discovery research.”