200 Years of Vaccination And Counting

It's crazy to think that we have had vaccines available to us since the late 1700's, yet we still have plenty of vaccine-preventable diseases floating around and causing outbreaks. (It's even crazier if you put it in terms of how much the United States spends on healthcare compared to the rest of the world.) Vaccines are one of those things that don't work as well as they should for a whole myriad of reasons. It's not just their technology but also societal attitudes towards them. From presidential candidates to the typical "soccer mom," vaccines seem to be a source of controversy when, in a perfect world, they would be no more controversial than whether or not to wear a helmet in outer space. They're necessary. They save lives.

But let's not invoke the spirit of Jenny McCarthy by talking about anti-vaccine people and their plots to destroy us all. Let's focus on the technology of vaccines and how it has changed over the years. After all, this is a technology site not a crunchy-granola-mom-and-dad-cloth-diapers-are-awesome site.
The first true vaccine was developed by Dr. Edward Jenner in 1798. In those days, smallpox was the one disease that everyone feared the most. It gave you fever, body aches, a horrible rash all over your body (but mostly on your face and extremities), and, if you were lucky to survive it, you were scarred for life from the pustules on your face. Before the Jenner vaccine, the only way to try and prevent it was to give people smallpox in a controlled way, a process called "variolation."

Variolation was kind of nuts, if you think about it. They would take pus from the pustules of a person with smallpox and put them on a needle. They would then push that needle into your skin a few times to make sure the pus got in there nice and good. This would give you either a local reaction and some generalized feeling of yuck... Or you got the full-blown smallpox. However, because variolation was done under the best controlled conditions at the time, you were less likely to die from it.
In fact, Benjamin Franklin wrote about variolation in a pamphlet in an effort to encourage more people to do it. See, his own son had died from smallpox, so Franklin became somewhat of an activist against smallpox. In the pamphlet, Franklin gives compelling evidence that variolation is preferable to natural infection. (I did a statistical analysis – on the back of a napkin – and posted it here.)

In the late 1700s, Dr. Edward Jenner made the observation that milkmaids were not catching smallpox like the rest of the population. When he interviewed them to see what made them so special, he realized that many of them had contracted cowpox, a disease similar to smallpox but much, much milder. It didn't lead to the pustules on the face and the scarring. (Milkmaids were said to be the most beautiful women at the time.) He theorized that the body's response to cowpox offered some sort of cross-protection against smallpox.

You have to remember that Jenner had no knowledge about immunology, the study of the body's immune system. His theory came from just basic observation and deduction, much like a good detective would come up with a theory of how to stop a murderer based on the murderer's victims. He didn't know that, indeed, cowpox triggered an immune response where antibodies were created which also reacted and neutralized the smallpox virus. A person contracting cowpox would be immune against smallpox because they would retain immune memory cells which would activate almost immediately when faced with smallpox and prevent the virus from replicating by coating it in antibodies.

To test his theory, Dr. Jenner asked a young boy by the name of James Phipps (and James' parents) to allow Jenner to inject cowpox pus into James and then, a few days later, perform the variolation procedure (injecting smallpox) on James to see what would happen. This was a huge gamble, and something that we probably could go to jail for doing nowadays. But those days were the "Wild West" days of science. You didn't need to worry about ethics.

James got the cowpox injection followed by variolation a few days later. Dr. Jenner observed and reported that the smallpox variolation had no effect. James did not have any reaction to the variolation. He completely fought off smallpox without showing any sign of even a mild smallpox infection. Upon hearing of this, physicians the world over began using cowpox to prevent smallpox. By the late 1960s, smallpox was eradicated from the face of the Earth. Today, there are only two places where you can find the smallpox virus being kept on life support: CDC in Atlanta, and the Russian bio-security labs in Koltsovo. (There's been plenty of calls for the two countries to destroy their stockpiles, but both keep them around in case of... Well, who knows? They just like to keep terror-inducing biological samples around, I guess.)

Since Dr. Jenner's discovery, there have been other vaccines created against many other diseases. They all work on a similar principle: exposure to a similar or weakened microbe (virus, bacteria, parasite, or fungus) will induce immunity without having to go through the disease. Newer technologies don't even use the whole microbe. They take only the proteins on the microbe's surface that will trigger immune responses and inject those into people. This is why vaccines like the one we use in the US for pertussis (whooping cough) or HPV (genital warts) cannot cause the disease they're meant to protect us from. Other vaccines use chemicals or heat to inactivate (kill) the microbe, allowing the human body to recognize and fight it without allowing the microbe to cause disease.
In some instances, injecting the whole microbe has proven to be somewhat detrimental to the person being injected.

For example, we used to have a whole-cell (whole-microbe) vaccine against pertussis. But some of the proteins on the surface of the pertussis bacteria are themselves toxins. If you got a pertussis injection with a whole-cell vaccine, you could have a bad reaction. The trade-off was that you were immune for a longer time. With the newer acellular (no microbe, only the proteins) vaccine against pertussis, the immune response is not as strong, and the immunity seems to wane over time.

Another vaccine technology that is out there is one where the microbe is injected into a large animal, like a horse. The animal's serum (the liquid part of blood, without the red blood cells and white blood cells) is then extracted from the animal and injected into a person. The animal's serum will contain antibodies against the microbe, so the person getting the serum will be infused with antibodies that circulate for a while, giving what is called "passive immunity."

More recent technologies have allowed us to create vaccines through the science (almost magic) of genetic manipulation. Genes that create a microbe's proteins are inserted into a harmless cell, like an insect cell. The insect cell then produces the proteins without producing the microbe. The proteins are then collected and given as the vaccine. This makes the chance of catching the disease from the microbe in question pretty much zero. It has also allowed people who are allergic to eggs (because flu vaccines are grown on eggs) to get the influenza vaccine without worrying that some of the egg made it through the final preparation process.

Speaking of influenza, one of the barriers to eradicating some diseases is their ability to have their surface proteins (antigens) change over time. Some do it better than others, and influenza does it really well. See, influenza is an RNA virus. This means that its genetic material is single-stranded, unlike DNA which is double-stranded. Two strands offer redundancy. If there is an error on one strand, the code on the second strand can be read instead. Because of its RNA, influenza has a very poor proofreading system. This leads to errors in the RNA as it is being copied to make new viruses, leading to new viruses with slightly altered antigens. Those altered antigens are not recognized by the antibodies created from previous exposure or previous vaccine. When this happens, it is called an antigenic "drift."

There are other occasions when two microbes of the same kind but different strain mix in one host and share their genes. The progeny of these two viruses is a third strain that could be completely new to a human population. When this happens, it is called an antigenic "shift," and it is one of main reasons why – from time to time – we have worldwide epidemics (aka "pandemics") of a "new" or "novel" microbe. We saw it in 2009 with influenza, and we are seeing the beginnings of it right now with the MERS Coronavirus coming out of the Middle East and starting to spread to humans who have never seen it before.

Of course, this is not all of the information that you should know to fully understand vaccine technology. There are other topics, such as infectious dose, herd immunity, and the R-naught number of a disease that you need to understand to truly be amazed at how far we have come from Jenner and how much work there is still to be done. I took this great course from Coursera a few years back, and it cemented all I need to know today as an epidemiologist. Perhaps it can inform you better if you're interested in learning more about the science and technology behind the vaccines that have saved millions of lives all these many years.