The Lost City of the Monkey God: A True Story(75)
Every strain in this library of parasites must be regularly recycled through mice to keep up its virulence. Otherwise it becomes “old,” weak, and useless for study. The protocols for animal research try as much as possible to avoid inhumane treatment; the suffering of the mice involved in the research, while mitigated as much as possible, is necessary in order to study and combat the disease. There are no alternatives to live research.
The sand flies and mice are kept in a biosafety level 2 lab. BSL-2 is for biological agents of “moderate potential hazard.” (There are four biosafety levels, BSL-1 to BSL-4.) I arrived at the lab during mealtime for the sand flies. A lab assistant brought me into the BSL-2 lab, which was a small room with a sealed door, a biohazard warning sign pasted on it. Below the symbol, taped to the door, was a soiled piece of paper with a giant picture of a sand fly and the name PHIL’S PHLY PHARM written underneath. Phil, I learned, was a scientist, long gone, who had helped develop the sand-fly feeding techniques.
No biohazard suit was necessary. I entered with some trepidation, glancing around nervously for loose flies, but they were safely shut away in stainless-steel, climate-controlled lockers. However, outside the lockers, a clear plastic box sat on a lab table, and inside was an off-putting sight: two anesthetized mice lying belly up, paws in the air, twitching. They were completely covered with feeding sand flies, whose tiny guts were expanding into bright red berries of blood. I shuddered, thinking of lying in my own tent, belly up and asleep, while the sand flies sucked my blood. These particular sand flies had not yet been infected with leish; once infected, they are handled more cautiously, not only because they can transmit disease but because they have become more valuable to science.
Later, these sand flies would be infected artificially, a complicated process. A delicate, hand-blown, tiny glass bottle has a piece of raw chicken skin stretched over it like a drumhead. This skin is moistened with mouse blood to fool the flies into thinking it is mammalian skin. The liquid inside the bottle is also mouse blood, seeded with the parasite. The sand fly jabs its proboscis through the chicken skin into the bottle and sucks up the blood and parasites. Once a sand fly is infected, the lab workers must then coax it into biting a live mouse, to transfer the infection. The target mouse is put in a tight Plexiglas box and its ear is held in a clamp attached to a small vial containing the infected flies. The hungry females fly down a tube, land on the mouse’s ear, and suck blood, transmitting the parasites to the mouse.
At the end of my tour, a lab assistant brought out two bottles of live leishmania parasites for me to look at under the microscope. They were living in a cloudy, reddish-orange nutrient broth. I peered into one of the bottles with a binocular microscope. As I focused the eyepieces, the parasites sprang into view, thousands of them in ceaseless motion, bumping into each other and going this way and that. They had elongated, pointy-headed bodies and whiplike flagellae, which are on the front of the cell and draw it forward instead of pushing it along from behind. For a while I watched the wriggling little buggers go about their business, thinking of the havoc they had wreaked on us.
The lab’s chief is Dr. David Sacks, a lean, handsome, plain-talking scientist who occupies a cluttered office in the basement. “These flies are just desperate for blood,” he told me. “They’re seeking any source and you folks just happened to be in the right place at the right time.”
Why, I asked, didn’t we all get sick? Why only half of us?
“I think all of you were bitten and infected,” he said. “I wouldn’t be surprised if a hundred percent of you were exposed, given the frequency of bites you seem to have had. So it’s actually more interesting why some of you didn’t develop lesions.”
He explained that one of medicine’s greatest mysteries is why some people get sick and others do not, given the same exposure. Environment and nutrition play a role in infection, but genetics are paramount. This is the very question at the heart of why so many New World people died of Old World disease. What was the actual genetic machinery that made some more susceptible than others?
With gene sequencing, Sacks said, we finally have the tools to figure out why some people are more vulnerable than others. Scientists are sequencing people’s entire genomes and comparing them, one against the other, to see what genetic differences pop out between those who, exposed to an infection, got sick and those who didn’t. We finally have the tools to understand the biology behind the great die-off and how such pandemics might be prevented in the future, but the research is still in its infancy.
During our exchange, when I made an offhand comment about how disgusting the flies were, he chided me: “Of course we don’t think they are disgusting at all. We love our flies.”
The leish lab, Sacks said, has been working for years on charting every stage in the life cycle of leishmania, looking for chinks in its armor that could be exploited by a vaccine. It’s harder to design a vaccine against a protozoan than against a simpler virus or bacterium; in fact, not one major parasitic disease has a reliable vaccine yet. Leish is very sophisticated in how it infects the body. It is, as one parasitologist said, “the royalty of the disease world.” Instead of wreaking carnage like many viral and bacterial diseases, and thus triggering a massive immune response, the parasites “try to have tea with your immune system.” Sacks and his team have identified the essential proteins the parasite uses during its life cycle inside the sand fly—and they’ve created mutant forms of those proteins that might block development. But figuring out how to exploit those vulnerabilities is hard, and getting from there to a vaccine is even harder.