Why Did the Chicken Cross the World? (9 page)

The eggs are the test tubes that produce the vaccine that inoculates us from influenza. Hippocrates described flu symptoms nearly twenty-­five hundred years ago, and pandemics were first recorded in the sixteenth century. In a normal year, the flu virus sickens millions and kills between 250,000 and 500,000 people. In the global pandemic of 1918, an estimated 50 million people died. About one in three humans fell ill, and five hundred thousand died in the United States alone. That pandemic may have begun in chickens, moved to pigs, and then spread to humans. Influenza appears to be a price humans have paid for domesticating animals, and the illness continues to evolve and spread among our species. A new pandemic is always a global threat.

Ironically, the chicken today provides us with our main source of the world's vaccine supply for a disease that continues to cycle between birds and humans. Combating this fast-evolving virus requires a concerted international effort by teams of doctors, epidemiologists, microbiologists, and public health officials. Each year, scientists around the world collect samples and make educated guesses as to which strains are likely to spread during the coming winter. The
vaccine uses tiny doses of the chosen inactivated strains to trick the body's immune system into producing antibodies, which can then fight off the infection when encountered during flu season. The selected viruses are cultured and sent to manufacturing plants like this one in Dresden.

Schu oversees the seven hundred workers who pump out 60 million doses annually and distribute them to seventy countries before the flu season takes hold. To do that, he needs a steady supply of ­fertilized chicken eggs. Each one must be kept scrupulously clean from the moment it is laid, and rigorous security precautions ensure a steady and sterile supply from farm to factory. Even he is forbidden from visiting the laying facilities. The farmers pledge to keep their work secret even from their neighbors, and no posted signs hint at their unusual product. Bacteria and virus brought by outsiders could delay or halt the clockwork production, endangering output and creating a potentially disastrous shortfall in global vaccine distribution. When a dangerous avian flu spread to a poultry operation close to one of the specialized farms in 2008, all the chickens in a ten-­kilometer radius were killed and Schu had to struggle to find eggs from other farms to make up for the shortfall. “That's why you don't put all your eggs in one basket,” he adds wryly.

As the driver shuts off the engine and climbs out of the cab for a smoke, Schu takes me into a small white-painted locker room in the main factory building. The vaccines are made in a sleek new glass-and-steel structure that takes in more than a third of a million eggs daily, each nearly identical in size and shape, laid almost exactly nine days earlier. Each has already been checked to ensure a regular shape and weight—only eggs that are fifty-four to sixty-two grams are ­acceptable—and that an embryo is developing.

Schu demonstrates how to wash hands thoroughly and slips his lean frame into a full white zippered jumpsuit and powder-blue booties to cover his bacteria-laden street shoes. Then he dons enormous clear goggles. This must be done without any article touching the floor contaminated by street shoes. It takes me twice as long to get into the awkward gear. Suited up, we sit on a bench dividing the room
in half, swing our legs over, and head for the only door on the other side. He pauses. “This is the last step before we enter areas with the active virus,” he says in a somber tone.

We enter a corridor and take an elevator to the third floor, where a long glassed-in hallway overlooks the loading dock below, which is more akin to the air lock in a spacecraft, providing a seal between the outside world and the eggs stacked inside the truck. At the end of the hallway, workers shrouded in the same coverings that we wear trundle spiffy stainless-steel versions of movable cafeteria cabinets, each containing hundreds of eggs nestled in plastic trays. In a small anteroom off the hallway, we put on yet another layer of gloves and booties.

When Schu opens the next door, we step into a small rectangular room with a wall of glass on one side, and a large door like that of an enormous walk-in freezer on the other. The place looks like a small, efficient institutional kitchen. Half a dozen women are busy moving trays filled with eggs as Schu opens the giant door. A blast of warm and humid air dissolves the Dresden chill still in my bones. Inside are racks and racks of eggs. The new arrivals are stacked in this enormous incubator overnight so that they can adjust after their bumpy journey.

Once the eggs have settled, the white-suited workers load the egg trays onto two conveyor belts that feed into a large room behind the glass. Resembling a modern German brewery with its stainless-steel tank for the live virus and assembly line machinery, it is off-limits to all but a small number of workers who oversee the operation of a steel needle filled with the virus solution that precisely and delicately punctures each egg. Then the ovum is incubated for up to ­seventy-two hours so that the injected virus can infect the embryo and multiply in the nutrient-rich but sterile environment. The fluid in the egg is harvested—chemicals render the virus inactive—­purified using high-speed centrifuges, separated into individual doses, squirted into syringes, shrink-wrapped, packaged, and distributed around the world. The flu shot that you get at the local drugstore can be traced back to a plant like this one.

The U.S. Army in World War II developed this technique amid
fears that a reprise of the 1918 pandemic might paralyze the war effort against German and Japanese forces. American soldiers received the first flu shots in 1945 as Dresden was firebombed by British and American planes. Millions of people have since avoided illness and death as a result of annual shots. Since each dose requires an average of three eggs, however, the process remains complicated and expensive. One egg infected with a pathogen can render useless an entire batch of vaccine.

Until recently, this has been the only practical way to produce large amounts of the vital medicine, but in late 2012, the U.S. Food and Drug Administration (FDA) approved an eggless vaccine that instead grows the virus in mammalian cells. Early the following year, the FDA also gave the green light for a simpler, less expensive process that doesn't even use live influenza virus. Instead a genetically modified virus infects the cells of insects to produce a protein that can trigger your immune system to make antibodies just like the egg-based version. “There will be a shift to an egg-free process,” Schu concedes as we take off our protective gear back in the factory locker room. “But the new approaches still have a number of hurdles to overcome.”

Even after the egg is no longer needed for influenza vaccines, it will remain the model animal research organism. Deceptively simple on the outside, this perfectly contained system is more complex than any pressurized spacecraft. Under its smooth exterior shell is an inner and outer membrane and an air cell that balloons at the flatter end to allow the system to expand and contract. Under this are two thin layers of slightly denser albumen—the egg white—encasing the clear liquid that takes up the bulk of the interior. Two strands of tissue connect the yolk, enveloped in its own membrane, to either end of the egg's interior. In a fertilized egg, the embryo feeds off the yolk, deposits waste in a sack, and takes in oxygen through the semipermeable shell that simultaneously keeps out any intruding bacteria or virus. Perfectly protected, the embryo has no need for an immune system and antibodies until three days before it hatches.

Aristotle studied chickens and in the process hatched embryology. He observed the mating habits of roosters kept apart from hens in
temples—possibly in the Athenian Asklepion that had chicken flocks for sacrifice. He also cut little holes into fertilized eggs so that he could record the growth of the embryo over the three weeks it takes for an egg to hatch. The observations allowed him to dismiss the notion, held by many scientists well into the nineteenth century, that the embryo was an animal in miniature that simply got bigger. Instead, the Greek thinker proposed that a fetus develops in clear stages. These innovative chicken-egg experiments led him to examine other species, including humans, until he concluded “all animals whatsoever, whether they fly or swim or walk upon dry land, whether they bring forth their young alive or in the egg, develop in the same way.”

The tiny universe of the chicken egg remains the miniature laboratory of choice for embryologists. William Harvey in seventeenth-­century London used the egg to understand how blood flows and to trace what became known as the nervous system. Marcello Malpighi at Bologna used the newfangled microscope to describe capillary vessels and other key elements of developing anatomy in chickens. Three centuries later, in 1931, scientists cultured viruses in fertilized chicken eggs, paving the way for the first cost-effective vaccines to combat mumps, chicken pox, smallpox, yellow fever, typhus, and even Rocky Mountain spotted fever—and, eventually, influenza.

By the 1950s, cancer researchers used chicken eggs to understand tumor development. By inserting cancer cells into a fertilized egg, they examined how the disease feeds and spreads. One of a new generation of scientists, Andries Zijlstra at Vanderbilt University Medical Center in Nashville, has found an innovative way to observe tumors grown inside an egg. “The trick has been to keep an animal alive while watching a tumor grow,” he tells me when I visit his lab, a short drive from the bars of the country music capital.

The son of a Dutch farmer, Zijlstra pioneered a way to decant a young embryo into a plastic petri dish without disturbing its growth by maintaining proper temperature and humidity. After injecting tumor cells into its blood vessels, he then takes a photo every fifteen minutes as the cancer cells proliferate, and watches how cells respond to cancer. In one corner of his lab, Zijlstra pulls out a rectangular tray
with a couple dozen shallow depressions, inside of which are bits of what look like orange Jell-O that has not quite hardened. “These need to cook for a few more days,” he says of the embryos, meaning that they require further incubation. His lab goes through twenty thousand eggs a year, produced in near-sterile conditions like those used in Dresden. A single one costs three dollars, about the average price of a dozen in a store. “With the chick embryo, you can actually see what is going on, unlike with a mouse or even a zebra fish,” he tells me as he slides the tray back into its warm and humid home. “It is a fully intact biological system, not one that has been chopped up into pieces.”

On October 30, 1878, a package containing the heart of a young rooster arrived at the Pasteur Institute in Paris. The bird had died in Toulouse after being injected with a deadly disease then sweeping French flocks. At that time, the only vaccines available were for illnesses like smallpox and cowpox. The unaltered virus usually stimulated antibodies and protected the patient, but it could also kill.

At first Louis Pasteur, a world-famous and busy scientist in his midfifties, paid little notice to the delivery. But his young assistant Charles Chamberland bought two live chickens in the Paris market and injected them with the virus drawn from the dead cock's heart. When he returned to the institute the next morning, they were both dead. Chamberland wanted to culture the microbe, but his efforts using a mixture of yeast and water failed. Just after New Year's Day 1879, he and Pasteur hit on that all-purpose remedy: chicken soup, or, more precisely, chicken broth. “We now have a culture medium for these little organisms,” Pasteur noted with excitement. The bacillus survived in the broth, since live chickens inoculated with it quickly expired.

They made no further progress until summer. Like most well-to-do Parisians, Chamberland was eager to begin his August vacation. Delaying plans to inoculate several hens with the “little organisms,” he absentmindedly left the broth sitting out near the chicken cages while away. When he finally got around to the task several weeks later,
the birds sickened but recovered. Intrigued, Pasteur ordered another set of injections. “Chance only favors the prepared mind,” Pasteur once said. When the birds did not die, and ones bought that day in the local market did, he realized that the original fowl had developed a resistance to the disease after being exposed to small amounts of the microbe drifting in the lab air during the summer break.

That revelation led to an intensive effort to manipulate the virus so that it would produce antibodies without turning lethal. The scientists experimented with increasing acidity and decreasing temperature in the infected broth and observed the resulting effect on the health of chickens procured from the markets. Exposing the bacillus to oxygen weakened its impact. By January of 1880, Pasteur was able to inoculate chickens—at one stage as many as eighty in cages at the lab—with the altered virus, which gave them immunity without making them ill. “Through certain changes in modes of culture development,” he triumphantly informed the Academy of Sciences the next month, “we can reduce the virulence of the infectious microbe.”