Once they’re activated, B cells spew antibodies out into the body, and depending on the particular antibody, they can fight the infection in several ways. They can cluster around a toxin made by bacteria and neutralize it. They can help the complement molecules trying to drill into the bacteria to make bigger holes. They can latch onto bacteria and foul up the chemistry they use to invade the body’s cells. They can tag bacteria to make them a clearer target for macrophages.
As the majority of B and T cells go about eradicating the bacteria from the cut, a few sit out the attack. These are known as memory cells; it is their job to preserve a record of the invader for many years after the infection. If the same kind of bacteria should get into the body again, the memory cells can switch back on and orchestrate a swift, overwhelming assault. These cells are the secret to vaccines. Even if immune cells are exposed only to an antigen, they can produce memory cells. Because a vaccine contains only a molecule and not a living organism, it doesn’t make a person sick, but it can still prime the immune system to wipe out the pathogen if it ever meets up with it again.
T cells, B cells, macrophages, complement molecules, antibodies, and all the other parts of the immune system form a tight net that perpetually sweeps our bodies clean. Every now and then, though, a parasite slips through and establishes itself. Its success isn’t simply due to some oversight but to the parasite’s ability to escape the immune system. Bacteria and viruses have their own tricks, but many of the most intriguing strategies are found among the “classic” parasites—the protozoa, flukes, tapeworms, and other eukaryotes. They can evade the immune system, distract it, wear it out, and even take control of it, confusing its signals into a weakened state or, if need be, a heightened one. One sign of the sophistication of these parasites is the fact that there is still no vaccine for them, while there are many vaccines for viruses and bacteria. If Lankester had known any of this, perhaps he wouldn’t have given parasites the bad reputation they still haven’t been able to shake.
In September 1909, a strong young man from Northumberland came down with sleeping sickness in northeastern Rhodesia, near the Luangwa River. His illness wasn’t diagnosed for two months, but soon afterward he arrived back in England, and was treated by doctors at the Liverpool School of Tropical Medicine. He was admitted to the Royal Southern Hospital on December 4, where his doctor was Major Ronald Ross. Ross was one of the giants of tropical medicine, who a decade earlier had figured out the cycle of malaria: the way Plasmodium travels between mosquito and human. The sleeping sickness patient’s blood was seething with the trypanosome parasites, thousands of augur-shaped creatures to every drop. His glands swelled, and his legs became covered in rashes. For weeks he dwindled. Ross tried to destroy the parasites with an arsenic compound but had to stop when it damaged the man’s eyes instead. In April, the patient vomited for four days and lost ten pounds. From then on, he became drowsier and drowsier, although he would occasionally perk up. His liver expanded, and the vessels in his brain became congested.
Ross began trying out other treatments. He inoculated a rat with the blood from his patient, let the parasites multiply, and then drew off some of the rat’s blood. He heated it to kill the trypanosomes, and then injected this crude vaccine back into the man. It did nothing. In May, his patient’s anal sphincter became paralyzed and Ross was sure he was going to die, but a week later he went through a sudden remarkable improvement. It lasted only a few days before he faded again, came down with pneumonia, and passed away. At the autopsy, Ross couldn’t find a single trypanosome.
A few years earlier, Ross had invented a quick way to detect blood parasites, and he used the method on the patient during his final three months. In the process he got the world’s first day-by-day portrait of sleeping sickness. He plotted it out on what he described in a report on his patient as a “remarkable graph.” The graph showed a clear rhythm: for a few days the trypanosomes would skyrocket, multiplying by as much as fifteen-fold. Then, just as suddenly, they would drop back down to barely detectable numbers. The cycle would take a week or so, and the man’s fevers and changing white blood cell counts followed in its wake. The man hadn’t been attacked by a single assault of parasites—a string of outbreaks had flared and died within him.
Ross saw in his patient “a struggle between the defensive powers of the infected body and the aggressive powers of the trypanosomes.” Exactly what the nature of that struggle was he couldn’t say. With another ninety years of study, scientists still can’t make a sleeping sickness vaccine, but they do at least understand how trypanosomes ride their spiky wave until their host dies. They play an exhausting game of bait-and-switch.
If you could fly Fantastic Voyage–style over a trypanosome, you’d be bored with the view. It would be like the drabbest cornfield in Iowa: millions of stalks all crammed together with barely a space between them. Fly to the next trypanosome and there’s no relief: the cornstalks would be identical with the first one. In fact, go to any of the millions upon millions of trypanosomes in a human host at any given moment, and you’ll most likely find the same coat.
For a human immune system, these parasites should be as easy to kill as fish in a barrel. If the immune system learns how to recognize only one of these cornstalk molecules, it can attack just about every parasite in the body. And indeed, as a host’s B cells begin to produce antibodies tailored to the cornstalks, the trypanosomes start to die. But not completely. Just when it looks as though the trypanosomes are about to disappear into obscurity, their numbers bottom out and rise again. The view has changed. If you were now to fly over the trypanosomes, you’d find not corn but wheat—an utterly drab expanse, but a completely different kind of expanse.
The quick change happens thanks to the unique way the trypanosome’s genes are laid out. The instructions for building the molecule that makes up the trypanosome’s coat sit on a single gene. Normally, when the trypanosome divides, the new parasites use that same gene to make the same coat. But once every ten thousand divisions or so, a trypanosome will abruptly retire the gene, cutting it out of its position in the parasite’s DNA. It then reaches into a reserve of a thousand other coat-building genes, selects one, and pastes it into the old gene’s position. The new gene starts making its surface molecule: a molecule that’s similar to the previous one, but not identical with it.
Now the immune system, so focused on the first coat, needs time to recognize the second one and make new antibodies for it. In that time, the trypanosomes with the new coat are safe, and they can multiply furiously. By the time the immune system catches up and is attacking the trypanosomes with a new antibody, another trypanosome has installed a third gene and is making a third coat. The chase goes on for months or years, the trypanosomes flinging off their coats and putting on new ones hundreds of times. With so many different kinds of trypanosome fragments building up in the bloodstream, the host’s immune system becomes chronically overstimulated, attacking its own body until the victim dies.
This bait-and-switch strategy works only because the parasite can dip into a reservoir of coat-producing genes. But these genes can’t be called from their bullpen in any random order. Say that the first generation of trypanosomes to get into a person’s body were to switch on all their coat-building genes. The immune system would make antibodies to all of them and bring the infection to a quick stop. And if a new generation of parasites were to turn back to an old coat gene, the immune system would still have some antibodies left over with which it could fight it. Instead, the trypanosomes carefully go through their lineup in a predetermined order. Take two trypanosome clones and infect two mice with them, and their descendants will switch on the same genes in the same order. That way, the parasite can stretch out its infection for months.