Stefan Kappe with Byron

Doing genetic crosses with model organisms is a basic lab protocol. “That's easy in mice, but it was virtually impossible in the parasite,” says Stefan Kappe, a parasitologist at the Center for Infectious Disease Research (CIDR) in Seattle, where he works on the Plasmodium falciparum parasite that causes malaria. He is also a faculty member in the University of Washington's Department of Global Health.

It has taken researchers nearly three decades to make three genetic crosses with the parasite, says Kappe, because the parasite needs a mammalian host to complete its life cycle. Sexual reproduction leads to recombinant progeny, which can help researchers study genetic factors that shape parasite biology. But obtaining these progeny would mean experimenting on chimpanzees, which Kappe rejects on ethical grounds.

In new work he, his colleague Ashley Vaughan and other Seattle team members as well as colleagues in Indiana, Texas and Thailand were able to retrieve recombinant progeny of the parasites from a hepatocyte-liver chimeric mouse model, that is, mice with a humanized liver. The researchers then cultured the recombinant parasites and analyzed clones to pinpoint the genetic underpinnings of drug resistance or to decipher how the parasites invade red blood cells.

One advantage of the new technique, says Kappe, is that it can be done by anyone seeking to analyze phenotypes and the associated genetic loci. In the past, scientists have sequenced the nonrecombinant genomes of parasites isolated from patients, but the huge genetic diversity of parasites presents a hurdle. With crosses, genes of interest can be pinpointed rapidly, he says, and can then be sequenced.

I'm a little bit of a chimera.

Kappe hopes that the new method will play an important role in research and help in finding an intervention that can address the “big killer” that is malaria, says Kappe. “I'm a little bit of a chimera,” he says. “I love to know that what I find in the laboratory can have an impact on human health.”

So much parasite biology remains to be explored. When infecting red blood cells, Plasmodium uses the cell's membrane as a kind of invisibility cloak. The membrane becomes a protective vacuole from which parasites exploit the host cell. “You just get hooked,” he says about seeing this invasion and takeover under the microscope.

Kappe's interest in parasites began when he was an undergraduate biology student in his native Germany. And they have held his fascination. After finishing his PhD in parasitology at the University of Notre Dame, he was a postdoctoral fellow at New York University School of Medicine, where he also held a faculty position, before he switched to CIDR.

Close encounters with malaria are regular events for Kappe. “When I'm in the field, I get bitten by malaria-infected mosquitoes all the time,” says Kappe. And he never forgets the price paid by those without access to treatment. In a hospital in Tanzania, he saw children with severe malaria in which the infection affects the brain. He knew this disease stage meant the children would not survive the night. “It is a life-changing experience when you see how these diseases affect people,” says Kappe.

Kappe travels extensively for his research throughout South America, Southeast Asia, and western and eastern Africa. “I love to see the world; I like to experience different cultures and environments,” says Kappe, who is an avid hiker and outdoorsman. He is also a passionate scuba diver. “Maybe I do it because you can't get bitten by mosquitoes underwater.”

Trekking in the wild is about calculated risk, but sometimes things do get dicey. While working with colleagues in Tanzania, he slept in a partially open hut. One morning he awoke to the sight of a venomous green mamba snaking its way through the thatched roof right above his cot. “I was shaken a little bit,” he says.

In casual conversation, Kappe is lighthearted and enjoys telling stories of his travel-related adventures and misadventures, says Alexis Kaushansky, a postdoctoral fellow in Kappe's lab. Switching the topic to malaria bumps up the conversation's intensity. Kappe is unwavering in his commitment to eradicating malaria. “As such, he has dedicated his life to the search for a malaria vaccine,” says Kaushansky.

As a mentor, Kappe “has far exceeded my expectations,” says Kaushansky. Kappe has stretched his thinking and challenged him, while retaining respect for his scientific approach and background. Kaushansky is about to start his own lab and is weighing his offers. Without a doubt, he says, Kappe “has made a huge contribution to who I am as a scientist.”