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Vaccines

Vaccines are a boot camp for the immune system. The inoculations prime and teach the immune system, effectively training the T cells and B cells and giving them a cheat sheet. The right vaccine can provide your body with the power to mount a faster response to diseases that could otherwise be deadly or devastating in other ways, whether smallpox or polio.

It’s not that our elegant defenses won’t mount an attack against these diseases absent a vaccine, but the attack might well be insufficient given the time it takes for the immune system to identify the bug and start manufacturing enough soldiers to fight back. In the meantime, you might well die. That said, it’s no small thing to find the right vaccine. The lesson of this chapter is that the immune system can learn, but it’s not easy to teach.

Among the most famous names in vaccines is Edward Jenner, the English doctor who developed the smallpox vaccine. Less well known is that the groundwork for Dr. Jenner’s discovery had been laid through various experiments aimed at stopping smallpox, the variola virus, which appears, according to the CDC, to have been around since Egyptian times (evidence: mummies with pustule scars).

Smallpox was spread through the air, by sneezes, coughs, or close interaction with a victim. It killed 30 percent of those who contracted it. Its lethality has to do with the way it and related viruses pull a stunt on the immune system. The infections can block the transmission of a distress signal that calls killer immune cells into action. (I’ll save this discussion of the way diseases trick the immune system because it relates in no small way to how immunology helped save Jason.)

Prior to the work done by Dr. Jenner, the effort to control smallpox was called variolation, the name drawn from the name of the virus. If you think vaccinations seem unpleasant nowadays, this precursor was worse. “Material from smallpox sores (pustules) was given to people who had never had smallpox. This was done either by scratching the material into the arm or inhaling it through the nose,” the CDC notes in a history of the technique. Unpleasant though it might’ve been, it did curb the likelihood of getting the disease in some people, though not enough to stop its epidemic spread.

To physicians and scientists of the period, it showed that the immune system seemed able to develop a response that could later be called into play. The system can acquire a cheat sheet that both helps to quickly identify a problem and has the instructions on how to immediately liquidate the foe. Variolation usually didn’t work, though. In most cases, the immune system didn’t get sufficiently educated to, or stimulated against, smallpox.

Then came a turning point for medicine.

The setting was Gloucestershire, England, in 1796. It is hallowed ground well-trodden in the history books. Dr. Jenner noticed that the cow’s milkmaids had pustules but didn’t seem to get the deadly disease. From a cowpox lesion of a milkmaid, he poisoned an eight-year-old boy. The boy lived. Somehow this cowpox strain was the right varietal to spark an immune system defense. Happy birthday, world’s first vaccine!

Even then, though, scientists understood that there was a corollary to the immune system’s ability to learn: It is not easily taught. As often as not, efforts to create vaccines failed. The concoction seemingly had to be perfect. Little changes could render inoculations ineffective. Researchers discovered that successful vaccines were strong enough to provoke a powerful response by the immune system, but weak enough—attenuated is the scientific term—to keep it from being as nasty as the infection itself. The wrong combination entailed the risk that, instead of protecting, a vaccine could kill.

That’s what happened with the initial mass test of the polio vaccine.

The first polio epidemic was recorded in 1894, 132 cases in Vermont. Of the infected, 1 to 2 percent were paralyzed.

The poliovirus gets quickly into the bloodstream, after entering through the mouth and growing in the throat and gastrointestinal tract. It winds up in the nervous system, where it attaches to nerve cells and invades them. It then takes over the nerve cell’s manufacturing process to reproduce itself—thousands of copies in an hour. Then it kills the cell and moves on to infect others. Picture a shadow creeping over our festival as cell after cell goes dark.

The vexing effort to eradicate polio included the work in the 1930s of two competing scientists, Dr. Maurice Brodie, a Canadian working at New York University, and a Philadelphia pathologist at Temple University in Philadelphia named Dr. John Kolmer. Various histories I’ll delineate here recount their failings, even disasters.

The two competing scientists had similar ideas. They infected monkeys with polio and tried to make a human vaccine with the nerve tissue. In Brodie’s case, he then mixed the liquefied monkey tissue with formaldehyde, called formalin, hoping to “deactivate” the virus. It would present enough, the theory went, to provoke an immune response, but would not be powerful enough to actually infect. Not so much. One history, written by a Yale doctor and historian named John Paul, is quoted as saying that Brodie’s vaccine was tested on 3,000 children, but “something went wrong, and Brodie’s vaccine was never used again.” A history published in the New York Times is more explicit: Children were left paralyzed.

Dr. Kolmer had the same results, though he took a slightly different approach. He took the monkey nerve tissue, mixed it with chemicals, and refrigerated the mixture to attenuate it. Dr. Paul’s history calls it a “veritable witch’s brew.” More infected children. In Paul’s book, Dr. Kolmer is reported to have said at a public health conference in 1953: “This is one time I wish the floor would open up and swallow me.”

In 1952, as Time magazine reported, the worst outbreak yet infected 58,000 Americans, killing 3,000 and paralyzing 21,000. “Parents were haunted by the stories of children stricken suddenly by the telltale cramps and fever,” Time read. “Public swimming pools were deserted for fear of contagion. And year after year polio delivered thousands of people into hospitals and wheelchairs, or into the nightmarish canisters called iron lungs.”

The answer to the polio mystery, also well known, came from Jonas Salk, who was born in New York City of Russian Jewish immigrant parents and eventually was appointed director of the Virus Research Laboratory at the University of Pittsburgh School of Medicine (by way of New York University and Michigan). His vaccine weakened the poliovirus with formaldehyde and mineral water. It effectively “killed” the poliovirus. But it was recognizable enough for the immune system to pick it up. Ta-da! It cut the risk of infection in half.

The country scrambled to produce and disseminate the vaccine as quickly as possible. Alas, this happy ending comes with an asterisk. The first big batch of vaccine wasn’t properly made. Cutter Laboratories in California, one of the main producers of the vaccine, inoculated more than 200,000 children in 1955, and within days there were reports of paralysis. Within a month, the program was discontinued, and investigations revealed that the Cutter vaccine had caused 40,000 cases of polio, leaving 200 children with varying degrees of paralysis and killing 10.

These problems were ironed out and polio was all but eradicated in the United States and, eventually, worldwide. Here’s the lesson: Intervening on behalf of the immune system is no easy task, given the delicate balance. The vaccines were the first big step in that direction, even if we didn’t truly understand their dynamic. Without fully understanding the mechanisms, we had found an effective tool.

That was true of the discovery of a second, marvelous immune system ally: antibiotics.

Early doses of penicillin, a medicine that changed the world. (Science Museum, London/Wellcome Collection)

Antibiotics are arguably more important than vaccines. In fact they are “probably the most successful forms of chemotherapy in the history of medicine. It is not necessary to reiterate here how many lives they have saved and how significantly they have contributed to the control of infectious diseases that were the leading causes of human morbidity and mortality for most of human existence,” according to a history published in a National Institutes of Health journal. Broadly, antibiotics work by taking advantage of differences between human cells and bacterial cells; for instance, bacterial cells have walls that human cells do not. Antibiotics can prevent bacteria from building such walls.

That’s the mechanism behind the shot heard ’round the world in 1928, at St. Mary’s Hospital at the University of London. The world was temporarily at peace, which was fine with a Scotsman named Dr. Alexander Fleming. He’d seen plenty of the opposite in the Army Medical Corps during the Great War.

The accident took place in a petri dish. It was filled with the strep bacteria he was studying. One day he noticed something odd. One area of the dish containing the deadly pathogen was suddenly free of bacteria. A closer looked showed it was being killed off by mold—“the mold had created a bacteria-free circle around itself,” read Fleming’s Nobel Prize biography in 1945. Why the Nobel?

He named the medicine born of that mold penicillin.

Whereas vaccines prompt our own response, antibiotics import a response from the outside, and that is an absolutely critical distinction for our everyday health. The reason is that when you add an outside force, you disrupt the natural order. Even if the goal is preservation of life, and even if it works, that doesn’t mean the process is without important risks. In the case of antibiotics, these terrific killers don’t just kill off bad bacteria; they target good stuff too, including bacteria crucial to your health and well-being.

If you’ve ever taken antibiotics and gotten diarrhea, you’re in good company. The antibiotics are killing off bacteria in your gut that help you digest. They are doing real damage inside your gut, even as they get rid of the pathogens that could turn off the lights in your Festival of Life. Later, I’ll get deeper into the importance of the daily and long-term health of your gut, the microbiome, but at the time that antibiotics first emerged and became wonder drugs, the concept was more basic: survive the infection to fight another day.

Now, because of Dr. Fleming, you wouldn’t die from getting a cut on your hand, or a small battlefield wound, ear infection, and on and on. Antibiotics have not only extended life but improved its quality by permitting myriad modern surgical procedures, like knee and hip replacements, which would be at extreme risk of infection absent these wonder drugs. Plus, antibiotics are used to keep livestock healthy, helping grow the food supply.

But vaccines and antibiotics weren’t easy to come by, at least not effective ones. The body had to do most of the work. It had been doing most of the work—for epochs.

Plus, the immunologists pioneering the exploration were determined to get deeper into the machine, for both intellectual reasons and practical ones—could they figure out how to extend life further and further? That meant answering the biggest question of all: how could our bodies become equipped with defenses for so many possible threats? How is it we can survive in a world in which the possible threats are practically infinite?