Prehistoric man - Homo sapiens, that is - was a hunter who devoured his meat raw, as did the rest of his cave-dwelling family. They didn't come down with toxoplasmosis, an infection of the protozoan parasite Toxoplasma gondii.
That was then. "Now" kicked in 10,000 years ago, when those Flintstony humans traded in their game animals for agriculture - farming their food. Nowadays, the Toxoplasma parasite infects most of the human race. Worldwide, 15 percent to 30 percent of that population has been exposed to this microorganism. In the U.S. alone, 35 million people carry the telltale T. gondii antibody - the smoking gun that's evidence they caught the infection at least once in their lives
A small minority - people with weakened immunity from AIDS, chemotherapy, immunosuppressive drugs - develop toxoplasmosis, a disease that can lead to birth defects, vision impairment and fatal encephalitis. But the majority hasn't much to worry about. Eating undercooked lamb chops, pork chops, chicken or venison can convey the microbe into their digestive tract, with virtually no symptoms. Just as likely, the infection can be acquired by accidentally swallowing spores from contaminated soil, water or contact with cat litter or tabby's feline feces.
The infective prowess of this parasitic protozoan has been blamed on a single genetic recombination that happened roughly 10,000 years ago, when human beings evolved from wild meat eaters to domesticating animals and cultivating plants. This seminal event freed T. gondii from sex, and made being eaten an attractive life option. Humans and other vertebrate hosts could catch toxoplasmosis by one of the new asexual parasitic clones lurking in intestines seeded with poorly cooked meat.
The unique exception was Felix catus, the cat - tamed those 10 millennia ago by those precocious farming humans to catch rats and mice, and as domestic pets.
No More Sex; Better Be Eaten
"The cat is important for the evolutionary recombination phase," observed molecular microbiologist L. David Sibley, at Washington University in St. Louis. "This phase happens in the cat's intestines," he continued. "Then they shed in their feces an environmentally resistant spore, which can also disseminate infection. So some infections are caused by contact with cat litter, or fecal contamination of food from cats or people. Cysts, unlike spores, are not free in the environment," he pointed out. "Cysts stay inside the animal, in its muscle.
"No one understands what gives the cat's tissues or genetics this unique infectivity," Sibley went on. "It's a property of nature. Toxoplasma will undergo an infectious phase in cats but not in dogs or other mammals." Sibley, whose research lab focuses on the Toxoplasma gondii parasite, is senior author of a paper in the current issue of Science, dated Jan. 17, 2003. Its title: "Recent expansion of Toxoplasma through enhanced oral transmission."
"Our main finding," he told BioWorld Today, "is that the T. gondii parasite is very widespread, and causes infection by a process where a person inadvertently ingests tissues found in rare meat that causes human infection in animals. Our study shows that this is a relatively recent evolutionary trait that arose in the last 10,000 years. The fact that it's a very ancient parasite means it's made a major change in its behavior the last 10,000 years. This is why it's found in virtually all warm-blooded vertebrates, and causes a very prevalent infection.
"The way we determined it," Sibley continued, "was to count how many mutations have occurred in this organism, as a way of dating. And because the mutations arise at a somewhat constant rate we could estimate the age of these very recent strains, and it was quite a surprise that they were so young. The ability to cause infection orally is not seen in related parasites, and was not seen in Toxoplasma until fairly recently
"This finding suggests that if it could happen in T. gondii, perhaps the change could occur in other, related parasites that infect animals - such as the malarial Plasmodium. This may be some kind of a warning, that we shouldn't underestimate these parasites as innocuous and stable, not of any consequence. Because they are there in our food chains where we're exposed to them when we eat undercooked meat, or contaminated water. And there's always the potential that they could change and become human pathogens.
"In in vivo experiments with mice," Sibley recounted, "we tested the animals' ability to cause Toxoplasma oral infection, by ingesting the tissue cysts from these parasites. When a rodent is infected, it must be eaten by a cat or a dog or a possum - a very specific host. Otherwise it's a dead end; nothing happens. In Toxoplasma, what's unusual is that mice are cannibalistic; they feed on each other, and so can pass the infection. If rats eat mice they, too, become infected."
From Orally Infected Mice To At-Risk Humans
"And if pigs catch rats and mice and eat them, they also spread the infection. So this is the trait that is so unusual. In all these other related parasites, if it goes into the wrong host it's a dead end. So what we're testing in our mouse model is if we fed them tissue cysts that came from the brains or muscle of mice, we asked, are they infectious or not?
"The answer is 'yes.' I'm not sure that the mouse is really a hazard in terms of spreading this infection in the environment," Sibley went on. "It's just a convenient model in the lab. Not that the mouse is a big threat but all these different infected animals can potentially infect people.
"Our ongoing research," he said, "is looking for the genes responsible for this trait. It's a small set of genes created by recombining a few of them in one background. And we can compare these newly derived strains, which have oral infectivity, with older strains that lack it. If we could identify those genes, they might be targets for a vaccination or some type of intervention to prevent the oral infection. Such a vaccine is pretty distant in the future," Sibley concluded. "For humans there is no current vaccine."