People, Parasites, and Plowshares

Learning from Our Body's Most Terrifying Invaders

Dickson Despommier

• Publisher: Columbia University Press
• Year: 2013
• ISBN:
  9780231535267
• Topic: Medizin
• Subtopic: Pathologie

Dickson D. Despommier's vivid, visceral account of the biology, behavior, and history of parasites follows the interplay between these fascinating life forms and human society over thousands of years. Despommier focuses on long-term host-parasite associations, which have evolved to avoid or even subvert the human immune system. Some parasites do great damage to their hosts, while others have signed a kind of "peace treaty" in exchange for their long lives within them. Many parasites also practice clever survival strategies that medical scientists hope to mimic as they search for treatments for Crohn's disease, food allergies, type 1 diabetes, organ transplantation, and other medical challenges.

Despommier concentrates on particularly remarkable and often highly pathogenic organisms, describing their lifecycles and the mechanisms they use to avoid elimination. He details their attack and survival plans and the nature of the illnesses they cause in general terms, enabling readers of all backgrounds to steal a glimpse into the secret work of such effective invaders. He also points to the cultural contexts in which these parasites thrive and reviews the current treatments available to defeat them. Encouraging scientists to continue to study these organisms even if their threat is largely contained, Despommier shows how closer dissection of the substances parasites produce to alter our response to them could help unravel some of our most complex medical conundrums.

1

THIS NEW HOUSE

Trichinella spiralis

Live Long and Prosper

All parasites fall into just two groups. They are either short-lived (days to weeks), or long-lived (months to years). The first group holds little interest for me, since they have invested so little evolutionary creativity scheming up ways to live inside us without killing or seriously hurting us in the process. They simply get in and do their job; reproduction at all costs. In the end, either we kill them or they kill us, and that’s that. The malarias (Plasmodia) fall into this category, and so do Giardia and Entamoeba histolytica, although these three can occasionally linger for up to several months in our blood or intestinal tract before we eventually fight them off. All these parasites happen to be single-cell organisms (protozoans). Granted, exposure to any parasite in this group could result in a protracted infection, but in the main, most of us manage to get rid of them in a relatively short period of time and go about our lives as if we had never encountered them. In contrast, there are some parasites that routinely stick around for months to years in our bodies and have acquired a toolbox full of chemicals and metabolic strategies that they employ to allow them to live long and prosper. It is this second group of organisms that never fails to hold my attention.

I spent the better part of my professional life, twenty-seven years, studying one of these long-lived creatures, and that is how I came to know and respect all of them for what they really are: superstars of the parasite world. Included in this long-lived group are the trypanosomes—both African (sleeping sickness) and American (Chagas’ disease) varieties—most of the leishmanias, Toxoplasma gondii, filarial roundworms (causative agents of elephantiasis and river blindness), the blood flukes (schistosomes), intestinal and tissue-dwelling trematodes, and the one I chose to study, Trichinella spiralis, the nematode responsible for trichinellosis (trichinosis).

Trichinella spiralis is a nematode that infects mostly mammals, but other members of the trichinella family infect birds and reptiles, too. Let’s take a moment to briefly describe what a nematode is before diving into my favorite subject. All nematodes are nonsegmented roundworms and include both parasitic and nonparasitic examples. In contrast, earthworms are segmented and nonparasitic. In fact, most nematode species are free living and are found in soil. Their ecological role is to help establish healthy growing conditions for most plant species. All nematodes, be they parasites or not, have plenty of biology in common, including their basic body plan—a nonsegmented tube consisting of a chemically resistant, tough outer coating called the cuticle; muscle cells for locomotion; a nervous system for sensing where they are in the environment; a robust reproductive system for producing lots of offspring; and an excretory system for handling liquid metabolic wastes. The great majority of nematodes are either male or female, and they achieve adulthood by a four-stage developmental program in which each progressive stage is preceded by shedding their cuticle to make room for the added growth and development of the next stage. Adult nematodes do not shed their cuticles, as they have achieved maximum growth by then.

Trichinella has a complex life cycle that is all about survival. It does not have a reputation as a killer, although it is fully capable of doing so if the victim eats enough raw meat (often pork, but the parasite is found in other meats too) containing an abundance of the larval stage. All trichinella really wants to do is infect a host and then be carried far away from the site of infection. So keeping the host alive for as long as possible is in its best interest. When an animal harboring the infective stage of trichinella eventually dies of something else, perhaps old age or at the hands of a predator, mammalian scavengers that consume the carcass will become infected, thus extending the geographic range of the parasite. As a result, some form of trichinella (there are currently eight known species) can be found in almost every corner of our planet, including such disparate locales as the jungles of Papua New Guinea, the Serengeti Plain of East Africa, and the Arctic tundra.

Most trichinella species infect more than one kind of host—black bear, cougar, walrus, hyena, human. Trichinella pseudospiralis infects birds and mammals. Trichinella occasionally even infects herbivores, since most grazers will eat meat when the opportunity arises. Parasitologists call this kind of generalist infectious agent “promiscuous” because of its adaptation to a broad range of host species. Trichinella will even infect bats, but this only occurs under laboratory conditions. The only mammals in which trichinella has not been found in nature are unusual ones: moles, shrews, anteaters, pangolins, echidnas, and platypuses, for example. All trichinella species infect the gut tract of their hosts as adult worms and produce live larvae that find their way to the striated muscle tissue, where they can live for up to twenty-five years. Amazingly, trichinella larvae can even live weeks beyond the life of its host—quite a remarkable feat when you think about what it means to be a parasite. So how does this ubiquitous worm engineer its own survival once it is eaten? Before I reveal some of its biological secrets, I’ll first describe how it was discovered, since it is this bit of history that kick-started the search for more parasites and put Trichinella spiralis on the map as a human pathogen.

Seeing Is Believing

The place was London, England, and the year was 1835. The last outbreak of the Black Death had occurred in 1665, and the streets of London were once again filled to the brim with the hustle and bustle of commerce and people. Nonetheless, the horrendously unsanitary urban environment that favored the spread of plague—raw garbage in the streets, with free-range rats and their fleas roaming around—had not changed much since those dark days. The rich managed to stay on their somewhat cleaner side of town, while the disadvantaged masses crowed into the filth-ridden downtown districts near the River Thames. Charles Dickens would later write vividly about all this in his classic A Tale of Two Cities (1859). Cholera would not arrive in London by boat from India for another two years, but other endemic diseases continued to spread and raise havoc with the general population. Tuberculosis and syphilis were rampant. Science-based medicine was in its infancy in 1835, and the germ theory of infection (the one that proved that microbes are the cause of many common illnesses), brought to light by gifted researchers like Louis Pasteur and Robert Koch, had yet to be demonstrated. So the actual cause of yellow fever, malaria, cholera, plague, syphilis, or tuberculosis remained a complete mystery. Nonetheless, with each new medical discovery, establishing a career as a physician became an increasingly attractive option to well-educated members of the public. It attracted James Paget, and thus begins our story.

We know who James Paget was because he became the most famous pathologist of his time and described in detail numerous chronic diseases, including the one that still bears his name. Later in his illustrious career he was knighted by Queen Victoria. However, his connection with the discovery of the worm we now call trichinella occurred when he was just a first-year medical student at St. Bartholomew’s Hospital, located in West Smithfield in London. All the city folk referred to the place simply as St. Bart’s, and I will, too. It is still there today and remains one of the finest hospitals in the United Kingdom.

It was a rainy Monday morning that February 2, as young James, along with his fellow medical students, stood in a tight semicircle in the autopsy room at St. Bart’s, observing the dissection of a 51-year-old bricklayer who had apparently succumbed to the ravages of consumption. Nothing unusual there, as death from tuberculosis was a common occurrence, not only in London, but throughout Europe too. The surgeons who were demonstrating that day were not pleased by what they encountered, but TB was not the cause of their discontent. They began the autopsy around 11:00 a.m., using beautifully handcrafted scalpels that were sharpened and maintained by the medical technicians back at the main hospital. As the pathologist/surgeons commenced to lay open the corpse, they immediately observed that the pressure they had to exert with their instruments to cut into the chest cavity was more than what was usually required. In fact, their instruments were being dulled by the simple act of drawing them across the unbroken skin and into the superficial muscles of the deceased construction worker. Swearing and cursing ensued, followed shortly thereafter by the throwing of dull-edged scalpels to the floor in disgust. Finally, after gaining access to the internal organs of the thoracic cavity and inserting his hand, one of instructors was heard to mutter, “Just as I thought. Another @#$%$#@# case of sandy diaphragm!” We know all this because young Paget kept an exquisitely detailed diary in which he wrote every day about the goings-on in medical school. He also wrote letters to his brother from time to time, especially when something unusual came his way. As it happened, this was to become one of those unforgettable moments.

The entourage of surgeons apparently had had enough, dulling nearly all their scalpels without much to show for it. “What causes sandy diaphragm?” Paget asked, but no one replied with the answer. Apparently, the surgeons at St. Bart’s were not terribly curious when it came to things outside their own narrow sphere of interest. Finally, in a fit of frustration, they abandoned the lesson altogether and headed straight out the door and off to lunch. The students followed suit—with the exception of a professor, Thomas Wormald (a most propitious name, under the ensuing circumstances), who had dutifully remained behind to help clean up the mess and make room for the next corpse. After everyone but Wormald had left, Paget circled back and snuck in to remove a small sample of the diaphragmatic muscle tissue, seeking satisfaction of his earlier question. Paget was odd man out in that regard, and his insatiable appetite for knowledge drove him to look for answers himself. We are forever in his debt for doing so, because in the end he succeeded.

The first-year medical student was in the habit of carrying a hand lens with him, and he used it now to partially satisfy his curiosity. James observed what he thought looked like tiny, wormlike critters within the small, white, sandy structures scattered throughout the piece of diaphragmatic tissue. To make sure of his observations, though, he needed to look at the sample using a microscope, so he hurried over to the British Museum of Natural History where one of those rare instruments was located. The one James knew about belonged to Robert Brown, a botanist, who himself became famous for identifying “Brownian motion,” a characteristic of small particle random motion that would later contribute to Einstein’s theory of relativity.

When Paget peered into Brown’s instrument at the snippet of muscle tissue, his original suspicion was confirmed. Worms indeed were the cause of sandy diaphragm. On February 6 he gave a small presentation on his discovery to the student club at St. Bart’s. In addition, he wrote his brother a letter, describing in some detail the worm and its surrounding tissue. So apparently Paget was the very first human ever to lay eyes on trichinella. Or was he?

When Paget had first removed the sample from the body and examined it with his hand lens, Wormald—who was still in the autopsy room—confronted him and demanded to know what he had just seen. The fledgling pathologist replied that he thought he had seen worms but needed to confirm it using a better instrument. Then and there, Wormald decided to take the issue of sandy diaphragm to a higher level. After James headed off to the museum, Wormald cut out another small piece of muscle tissue from the same anatomic location and rushed it over to his good friend Sir Richard Owen, none other than the director of the very same British Museum of Natural History. Owen had a better, more powerful microscope than Brown’s and ultimately saw more details of the worms and tissue structures than Paget had observed. That day, Owen sat down and made a series of drawings of what he had seen and hurriedly wrote a paper on it, submitting it to the Royal Society for presentation. He knew of Paget’s original observations as described to him by Wormald but gave the medical student little credit in his tome on the subject. Owen named the parasite Trichina spiralis because the hairlike worms were coiled up in a spiral configuration inside their microscopic homes, which Owen referred to as “cysts.” The parasite’s name was later changed to Trichinella spiralis when it was discovered that another organism had already been designated Trichina (Greek for “little hair”).

The Rest Is History, Too

Some of you may recall that it was also Sir Richard Owen who vehemently opposed Charles Darwin’s concepts of how species arise and used a religious argument as his main strategy of attacking Darwinian reasoning. Owen used every public opportunity to dissuade the listeners as to the validity of that world-changing idea. He even went so far as to surgically alter the brain of the only known lowland gorilla to make it look anatomically different from that of a human brain, thereby “proving” Darwin wrong once and for all as to our apelike origins. It was up to Thomas Huxley, known as “Darwin’s bulldog,” to get his hands on a second gorilla brain and show that it was indistinguishable in every way from that of a human’s. Shortly thereafter, Owen was discredited in a public debate with Huxley. He then resigned his position at the museum and retreated from science altogether, never to be heard from again. To this day, however, Owen is still given the lion’s share of the glory associated with the discovery of Trichinella spiralis. In 1996 I visited that fabled museum and inquired as to the whereabouts of the original sample of diaphragm from which Owen made his observations, but I was told by the curator of helminths that, alas, a German bomb had destroyed the Duveen Gallery in 1940 with the specimen in it.

In the ensuing fifty years following its discovery, many eminent scientists worked on elucidating the details of trichinella’s life cycle, examining its medical relevance to disease, and exploring the epidemiology of how this unique nematode parasite spreads from animals to people. Today we know a great deal about all phases of its life, and with the completion of the sequencing of its genome in 2011, we will undoubtedly know much more in the coming few years. In the meantime, I will summarize its complex home-building activities in the host’s muscle tissue, and show how we might take advantage of this knowledge to solve some of our own medical problems.

Life in the Raw

As mentioned earlier, trichinella is not just one species as originally thought, but rather eight separate ones, and we will probably discover new members of that worm family the more we look for them. However, I will only discuss the biology of T. spiralis, since it is the most commonly occurring member of the trichinella family, and therefore the best studied. It is also the one most responsible for infecting humans.

Its life in a new host begins with the ingestion of raw, infected meat (fig.1.1). While it is in the meat, it is a larva or immature worm, the one Paget and Owen first saw. It is encapsulated inside a specialized host cell termed the Nurse cell. It is this structure that calcifies in old infections (thirty years in humans), causing the “sandiness” that the St. Bart’s surgeons dulled their scalpels on. Their blades were, in fact, encountering the petrified homes of the parasite.

That we can become infected by eating meat bought at the grocery store says a lot about how this worm is able to survive in the wild as well. After all, ground pork does not qualify as a living entity! In nature the worm is able to hunker down and ride out the time it takes an average carcass to become consumed by mammalian scavengers, such as bears, coyotes, or wolves. Larvae can survive for up to a month in a dead animal at low temperatures. Animals that hibernate have a natural antifreeze molecule to help them survive the cold winters, and this same molecule also protects some species of trichinella, if the worms should also become frozen. Trichinella spiralis is an exception, luckily for us, and is easily killed by freezing.

After an infected piece of meat is swallowed, the worms are released from their Nurse cells by our stomach acid and by pepsin, a digestive enzyme that dissolves the meat portion of the meal but spares the parasites. Trichinella is able to survive because ...