The Itch to Heal

When the mosquitoes arrive in Seattle, it’s all hands on deck. 

These insects are infected with Plasmodium vivax, a single-celled microorganism that causes a relapsing form of malaria. The pathogen’s journey begins in clinics and field sites in rural Thailand, where malaria patients donate vials of blood. At a lab in Bangkok, scientists feed the blood to mosquitoes, which are flown, alive, to Seattle. 

“When they get to us, we dissect them,” says Elzani van Zyl ’17, MS ’19, PhD ’23, an Invent at Seattle Children’s Postdoctoral Scholar in the Center for Global Infectious Disease Research at Seattle Children’s Hospital. Her team needs to isolate the insects’ salivary glands, where the parasites are hiding out, waiting for the mosquitoes to make their next blood meal so their life cycle can continue in a new host. The glands are impossibly small, and isolating them can be tricky—plus it has to be done fast.

This intricate work is worth it if van Zyl and her fellow scientists can find a solution to an ancient disease that, according to the World Health Organization, infects more than 250 million people each year. The vast majority of sufferers live in Africa, where children under 5 years old account for more than three-quarters of global malaria fatalities. Van Zyl brings to the work a passion born of her South African childhood, a desire to quickly translate research into clinical treatments, and a talent for unconventional thinking, fine-tuned over a decade at WPI.

The P. vivax organism is prevalent in Asia and South America, and while it’s not as deadly as P. falciparum, the dominant strain in Africa, it can be a trickier target for pharmaceuticals because of its complicated life cycle. When an infected mosquito bites a person, the parasite travels to the liver, where it develops asymptomatically for about two weeks before entering the blood stream and triggering an immune reaction that leads to fever, headache, and chills. As the parasite damages red blood cells, cases can progress to extreme fatigue, impaired consciousness, convulsions, jaundice, bleeding, and difficulty breathing. But even after a sufferer recovers, more P. vivax can be lying dormant in the liver, where it may emerge again weeks, months, or even years later.

Most existing malaria drugs only work in the bloodstream, meaning that even after being successfully treated, a person with P. vivax can become infected—and ill—again at any time. Two medicines target the parasite in the liver, but roughly 30% of people living in endemic regions have a genetic variant that prevents them from safely metabolizing the drugs. Because such patients could experience hemolytic anemia—the destruction of red blood cells—these treatments can’t be given to anyone who hasn’t been screened for that anomaly. But diligent screening can be hard to do in, say, a bare-bones clinic in rural Thailand.

“That means you are just kind of left to suffer with recurrent malaria,” says van Zyl, who is seeking a new drug that would be safe for everybody. And that’s where the mosquitoes come in: The pathogens in their salivary glands are vital for testing better cures.

The goal, van Zyl says, is to submit their findings early next year, when the group issues its annual call for proposals.

“They have a set criteria for what they want your compounds to be able to do, including the potency or selectivity, before you submit them to their pipeline,” she explains. “And then they help with the additional development of the drug. So we’re hoping by January of 2026 we’ll be at that point. That is the hope!”

Hope is a major theme in malaria research—and not only because of the scientific challenges presented by this complicated disease, but also because even a drug that works perfectly in the lab still has to work in the field. Malaria primarily affects people in the developing world, where access to healthcare may be sporadic and incomplete. Effective treatments must be stable for a long time at room temperature so that isolated clinics, which may not have refrigerators or even electricity, can keep a supply on hand. Patients might have trouble complying with a lengthy course of treatment or returning to the clinic for follow-up care, so, ideally, only a few doses should be required to do the job. Most importantly, new drugs have to be cheap.

“You need to be able to make something that can be given to individuals who are living on less than $2 a day,” van Zyl says. “You don’t have the big pharma companies investing a lot in this research, because it’s not a moneymaker. That’s disheartening, but it definitely makes us more invigorated to continue the work that we’re doing.”

Van Zyl’s interest in treatments that can help people in developing countries dates back to her childhood, where—like many other South Africans at the time—she was captivated by the dramatic story of Isabella “Pippie” Kruger, who was just 2 years old in 2011 when a bottle of fire starter gel exploded at a family barbecue, burning 80% of her body. The local press covered the girl’s story of miraculous survival, followed by setbacks and then a pioneering skin graft that saved her life.

The procedure, called a cultured epidermal autograft, involved cloning what remained of the toddler’s own skin. Developed by Genzyme, a Cambridge-based biotech company, it was extremely expensive and had only ever been done in the United States. Pippie’s family could afford it only with help from online donations, and, even then, there was no guarantee it would work.

“I remember the entire country was waiting, just holding its breath,” van Zyl says. “The samples were being flown over, and they needed to be grafted onto Pippie within 24 hours. Thankfully they were effective, and Pippie is still alive today because of them.”

It wound up being the right choice, and van Zyl would stay another decade, earning her BS, MS, and PhD in Biomedical Engineering. As an undergraduate, she worked in the lab of Professor George Pins, who co-supervised her Major Qualifying Project with Associate Professor Jeannine Coburn. For graduate school, van Zyl moved into Coburn’s lab, where she became involved with an innovative line of research that originated with a surprising source.

“She brought her kombucha to the lab and told me that this was now going to be my project,” van Zyl says, with a laugh. “And so things really kind of progressed from there.”

A fermented tea drink with alleged probiotic qualities, kombucha is created using a symbiotic culture of bacteria and yeasts, known affectionately as a “SCOBY.” Coburn had been brewing and bottling kombucha when she noticed an intriguing clear membrane on top of the bottled kombucha. She was interested in applying materials derived from nature to human health, and the clear membrane seemed promising, so she suggested van Zyl look into it. Van Zyl, remembering little Pippie’s ordeal, immediately saw the polymer’s potential as a transparent wound dressing.

“She was passionate about the project from a personal perspective as well, which I find valuable,” Coburn remembers. “It helps drive what you do. In my mind, a PhD student should be bringing their own direction to projects, and I like to foster that as much as I can—and as much as a student is willing to embrace it in my lab. That passion was one thing that stood out with Elzani.”

The kombucha-inspired research helped Coburn earn a prestigious CAREER Award, for early-career faculty, from the National Science Foundation, and she is still pursuing its potential with an eye toward real-world applications. That might take a decade or more, though, and there will be economic and regulatory hurdles to overcome even if the science is solid. As van Zyl completed the work for her PhD, she and Coburn began talking about the next steps—and van Zyl recognized that her own passion for getting cures to the patients meant she needed to see results sooner. Both women thought a career in industry would be her best option. But then van Zyl learned about the newly created Invent program at Seattle Children’s.

“Originally, when she said she wanted to do a postdoc, I was surprised,” Coburn admits. “A traditional postdoc leads to academia, and I knew she wanted to see treatments translated to the clinic now. But when she told me about this postdoc and the type of experience she would get there, I said, ‘Yes, that’s the right one for you!’”

When the Invent at Seattle Children’s Postdoctoral Scholars Program launched in 2023, van Zyl was one of the first 10 postdocs. This year, there are 26 scholars representing 10 different countries, including five from Africa. Each has their own laboratory, as well as clinical and biotech mentors who can offer perspectives from academia and industry and help the postdocs chart careers. The program also covers continuing education, and van Zyl is pursuing a professional certificate in drug discovery and development through the University of California San Diego’s online program.

“There are a lot of different avenues that I could go down,” she says. “But I like the feeling that I’m able to do something for people.”