Jayne Raper believes that to truly help people, sometimes you have to start with another species. In this case, cows.
Unlike Raper, a parasite researcher at New York University, most scientists who want to help people suffering from African sleeping sickness are trying to develop new drugs that fare better than the expensive, toxic treatments on the market. But this approach might not be good enough, especially since the rural Kenyan farmers coping with African sleeping sickness have concerns beyond their own health: their cattle, which also catch the disease.
While African sleeping sickness kills around 60,000 people per year, the cattle variant, called nagana, can wipe out up to 40 percent of livestock in endemic areas. Raper wants to create cattle armed with a gene that makes them immune to the disease.
She’s been planning the project since 2006, when she attended a workshop in Nairobi. At the meeting, local farmers explained how they need cattle to survive. Most of them can’t afford to eat meat or drink milk, but instead use cattle to plough their fields. Unfortunately, cattle also act as a reservoir for sleeping sickness, which is caused by trypanosomes, a parasite transmitted between humans and cows by the tsetse fly. Raper believes that introducing immune cows to tropical Africa, starting with Kenya, will reduce the number of infected people and save their cows.
“I had no idea how much people relied on them for sustenance until I went there,” she says. “Since then, I’ve been absolutely determined to make this cow.”
Cattle can be infected by four species of trypanosomes. Humans have a gene that protects them against infection from two of these species. At first, Raper thought she could somehow transfer the human immunity gene to the cattle. If she did, the cattle would still contract the kinds of sleeping sickness that humans could also catch. The cows would then transmit the disease more frequently—via flies—to people, undermining her goal. But this past year, she discovered a major clue, floating in the fluid between baboon blood cells.
Researchers have long been aware that baboons are immune to African sleeping sickness, but no one knew why. Raper suspected that a baboon gene might help kill all strains of the parasite the same way that a human gene kills two.
The trypanosome-fighting compound in humans is called apoL-1. It’s part fat and part protein, known as a lipoprotein. ApoL-1 is one of many lipoproteins that compose the high-density lipoprotein (HDL) complex, better known as “good cholesterol,” that transports fat in the bloodstream.
Trypanosomes enter the bloodstream after the tsetse fly bites its host. If the parasite is resistant to apoL-1, it will travel through the blood to the brain. Once there, it disrupts the host’s sleeping cycle, causing lethargy during the day and insomnia at night. If untreated, the disease culminates in a fatal coma.
In humans, certain species of trypanosomes are vulnerable to the apoL-1 compound. These parasites consume apoL-1, and the lipoprotein then forms pores that destroy the trypanosome’s cells from the inside, protecting the host from infection.
To figure out which baboon gene is responsible for killing off trypanosomes, Raper imported a quarter-cup of blood plasma from a colony of baboons living in Texas. After scouring the genes in the plasma, she and her graduate student Russell Thompson found one that was 60 percent similar to the human apoL-1 gene. Next, Raper needed to prove that the baboon gene killed typanosomes, so she artificially prompted engineered lab mice to carry the gene. Then she exposed the genetically modified mice, as well as a control group, to the four species of trypanosomes that infect cows.
She found that mice treated with the baboon equivalent of apoL-1 survived for over 100 days after exposure, proving the gene was protective. Mice without the gene died within a week.
But Raper still needs to figure out if a gene that works in mice will also work in a cow. To do so, she will collaborate with veterinarians, experts in genetically engineered cattle and members of the International Livestock Research Institute (ILRI) in Nairobi, a non-profit organization that helps local people by improving livestock quality. If Raper can make an immune cow, she will transfer the operation to the ILRI, which is equipped to create GM cows in Kenya.
To make an African sleeping sickness-resistant cow, researchers would inject the baboon immunity gene into the nucleus of an adult cow cell. Next, scientists would transfer the modified nucleus into the hollowed-out egg cell of another cow. This modified egg would then be implanted into a surrogate mother. If all goes well, the mother cow would give birth to a healthy, sleeping sickness-resistant calf.
Surprisingly, producing the cow isn’t the biggest obstacle. “It’s very reasonable to think that it would work,” says Mark Westhusin, a professor of veterinary physiology at Texas A&M University. He’s currently working to create cattle resistant to mad cow disease and foot and mouth disease. Researchers across the country are involved in projects using this kind of technology, and have been since the first transgenic cow was made about eight years ago.
For Raper’s project, though, “there’s a huge leap between getting the cow and helping poor farmers out in the field,” says Steve Kemp, a project leader at ILRI. Kemp says that even if the ILRI could produce sleeping sickness-resistant cows, it would have to transport the cattle to the farmers who need them, and many don’t live by developed roads. It’s crucial to inform local people about the research, he says, and that issue must be written into Raper’s project proposal. “It’s certainly worth doing, but it’s not trivial to do.”
And it’s an admirable enterprise, adds James Bangs, a trypanosome researcher at the University of Wisconsin-Madison. The parasite is so interesting for trypanosome researchers to study, he says, that “we forget sometimes that these critters are out killing people and livestock and making life miserable for up to 60 million people in sub-Saharan Africa.”
For now, Raper is the only trypanosome researcher pushing for a genetically modified cow. In fact, she’s the only one who has looked in non-human primates to try to crack the secrets of trypanosome immunity, Bangs says. “She’s made some really good contributions, and she’s done it by thinking a little bit outside the box.”