Herd Immunity

Life, disease and death in the 1630s

Imagining life in a small town in Germany in the 1630s is difficult for the average twenty-first century dweller. Picture awaking from an interrupted night’s sleep, courtesy of the local swine brawling in the alley below your bedroom window. Extracting yourself carefully from between the siblings sharing the bed with you, you arise and count your bedbug bites.

This may sound crude and uncivilized, but they were the plain facts of awakening in that day and age. Bedbugs, communal sleeping, bedpans, contaminated drinking water and lack of personal hygiene were commonplace, depending on where you lived. This also meant that disease was rife, childhood mortality was through the roof, and overall life expectancy in Germany during the Thirty Years’ war was less than that of the Roman era.

In the cities, the death rate usually exceeded the birth rate. It was in the cities that epidemics of plague, typhoid, smallpox and many other diseases ran rampant. For example, the plague hit the city of Amsterdam multiple times in the 1600s. This caused a loss of about twenty percent of the population each time the plague hit in 1624-25, 1635-36, 1655 and 1664.

Nonetheless, the population of Amsterdam had grown from 60,000 in 1600 to double that by 1632 and to 200,000 by 1670. This was in spite of the loss to disease. That many cities grew in this period of history was due to immigration from other cities or from the rural population. Rural communities, while by no means healthy by twenty-first century standards, suffered less from the continued onslaught of disease than the cities did.

Medical treatment

On top of having a far greater chance of coming down with a disease, there were few remedies that were known to be effective for many of the diseases. Many people used folk remedies which were passed down along the generations or adopted from friends or neighbors. Some of these folk remedies survive to this day, such as chamomile tea for soothing the stomach and nerves, or willow bark tea as a pain reliever and to reduce inflammation.

Often, ingredients were picked because of the physical appearance of the source of the ingredient For example, walnuts were thought to have the “signature of the head.” Some of these remedies were effective because at least one ingredient contained a suitable active agent (e.g., salicylates in willow bark). The problem then was with dosage control (a particular problem with the digoxin content of digitalis).

If Grandma’s home remedy didn’t work, you had to consult a medical professional. Regular doctors, trained at university, were often unavailable to most of the population. Cambridge and Oxford universities, for example, graduated on average just one MD per year.

The MDs mostly learned “classical” medicine, based upon the Greek physicians Galen and Hippocrates. These ancient physicians emphasized knowledge of the “humors,” which constituted the fluid contents of the body, such as bile, blood and phlegm. Disease was thought to be the result of an imbalance in the humors, which could be detected by studying the patient’s bodily functions. Their prescriptions often consisted of purgatories, enemas and/or bleeding their patients, to “purge” the patient of the bad unbalanced humors. It must be admitted that their teachings went beyond this, and many aspects still make sense now, such as advocating a balanced diet.

Unfortunately, even Galen made mistakes. For example, in his time, vivisection or dissection of human bodies was forbidden and he studied his anatomy on pigs. This meant that the Renaissance anatomists ran into a few differences when they started their dissections of real human bodies. Nonetheless Galen’s teachings were still adhered to, in spite of being wrong.

Worse, the MDs “cures” were often life-threatening in their own right. Consequently, the general population, even if able to afford access to MDs, might avoid them like the plague.

Consider Dr. Symcott’s treatment of the younger son of the Earl of Bridgewater, who suffered an apparent stroke. Symcott describes blowing tobacco and sneezing powder up the patient’s nostrils, putting mustard and vinegar in his mouth, administering enemas and suppositories, applying dead pigeons to his feet, holding a hot frying pan close to his head and finally leeches to his rectum. It is no surprise that the patient died.

When Symcott himself came down with gout, his brother, a London merchant, felt free to give him advice on how to treat it, thus exemplifying how much lay people held university trained doctors in contempt.

There were some notable exceptions, however. Graduates of Padua, Leiden and Edinburgh received more practical anatomy lessons than those who attended Paris, Cambridge or Oxford. Also, doctors trained in Arabic medicine tended to have a more rounded and generally more scientific underlying education which included, for example, keeping instruments clean for surgery. Many of these doctors were either Jewish or recent Iberian Jewish “converts” to Christianity. Their superior track record led to them being retained as court physicians, even for the pope.

Aside from regular university trained doctors, MDs, there were numerous lay physicians. This is a catch-all term which includes barber-surgeons, midwives, herbalists (who include “white witches”), and even bath attendants and executioners. The lay physicians by far outnumbered MDs, and were more deeply rooted in the community. Many of these had practical experience which made them more effective than the MDs. Hence, they had plenty of patients.

Since the MDs didn’t appreciate this competition, they did everything in their power to exclude the opposition. For example, a century before the Ring of Fire, in the aftermath of Columbus’ travel to the New World, there was a syphilis outbreak that hit—among other places—the papal court. Two court physicians, Torrella and Pintor, managed, with a varied degree of success, to treat this disease with metallic mercury, as well as other corrosive and abrasive substances, such as calcium oxide (similar to drain cleaner), ammonia and vitriol (acid).

One of the difficulties with using mercury was that it was a substance known to be used by many lay physicians in treating skin conditions. The MDs didn’t want the lay physicians to be able to treat the skin lesions of syphilis. They pointed out to the powers-that-be that mercury has rather severe side effects which could impair the mental health of the patient or even kill him/her. Hence, they contrived that the “professional and safe” use of mercury would be the sole realm of the trained MD.

There were many women among the lay physicians. Treating the sick was one of the few niches a woman could work in, especially when left destitute by widowhood. This, combined with their common practical education in midwifery or in herbology, and the fact that they would charge far less, frequently made these women more successful in treating the sick than the MDs. Consequently, they were denounced by the MDs. In the 1630s, James Primrose, an English MD, published a pamphlet, “Popular Errours,” which was very critical of female practitioners.

The tale of Madame Louise Bourgeois shows how much power the MDs had and how willing they were to use it against women practitioners, even when the MDs were in the wrong. Madame Bourgeois had been the royal midwife since 1601 when she attended the delivery of a French princess, the sister-in-law of the king, in 1627. There were six doctors present. When the princess died a week later, the “learned” doctors did an autopsy and laid the blame at the feet of the midwife, so as to exonerate themselves. The midwife, with all her practical experience, wrote a very extensive reply in defense of her reputation. She brought forth an overwhelming amount of evidence showing that the princess was suffering from a massive abdominal infection in her last trimester, but had no sign of that infection in her uterus. She completely refuted the doctor’s claims that the princess died from having incompletely passed the placenta at birth. Scientifically and medically she was correct as far as we can evaluate the evidence through the eyes of history. The doctor’s responses to her refutation of the autopsy report was little more than “Woman, you don’t know your place, shut up or we shall try and get you killed.” Such was the influence of the court physicians that the increasing attacks forced her to end her career at the French court.

This battle would continue until the MDs finally managed to achieve a virtual monopoly on “healing” during the Victorian era. Whether or not they were more successful at curing people by that time is debatable, but they certainly won the propaganda war.

How would the Ring of Fire change medicine?

One seemingly small, but in fact huge, contribution Grantville would bring is a concept in modern science that is called the “Scientific Method.” Originally, Descartes outlined the main tenets of this method in his 1637 book, Discourse on Method. One basic principle that is requested of anyone asking a question scientifically is to be objective. This is very difficult because virtually everyone makes assumptions of some kind and some of these assumptions inevitably end up being wrong. The scientific method further declares that any theory or hypothesis, a suggested explanation of a phenomenon, should be testable. The method involves a number of other principles, such as: “cause and effect” have to follow one another and plausible alternatives have to be eliminated.

For example, whether the active ingredient in willow bark extract, aspirin, does not relieve pain is a testable hypothesis. The experimenter would think about what factors, other than the aspirin, could affect the outcome. This would probably result in an experimental design in which one group of people (the treatment group) gets the aspirin and another group (the control group) gets a sugar pill.

All of the groups must be of people who are already in pain and are suffering of similar levels of pain. An example could be to test the relief of acute pain, such as after receiving an injection or chronic pain, such as from arthritis or migraines. The groups must be sufficiently large so that if there is a difference in outcome (pain relief or not) between the groups, the experimenter can fairly infer that this is attributable to the difference in exposure (aspirin versus sugar pill).

Ideally, the experiment is what is called double-blind. That is, the subjects don’t know if they are getting the treatment or the control, and the experimenter who records the outcomes doesn’t know which subjects get what, either.

If the treatment group exhibits more pain relief, and the difference is significant, then you can infer that the hypothesis that aspirin does not relieve pain is incorrect. That doesn’t mean it is proven that aspirin relieved pain in the sense that a mathematical theorem is proven. Rather, it means that the probability that the difference was the result of chance variation in pain subsidence is very small.

Likewise, if there isn’t a statistically significant difference between the two groups, that doesn’t absolutely prove the hypothesis. Chance variation could have swamped the positive effect of aspirin if the sample groups were too small. For example, a study might only include four people. Two of these people get a sugar pill but still claim to have a degree of pain relief, as do the two people who had aspirin. This means there was no difference in the result. However, if one does these kinds of studies with hundreds or thousands of people, clear differences in the effectiveness of a drug as compared to a placebo can be shown.

Thus, when plausible alternatives have been disproved (in the practical, not the absolute, sense) and the cause and effect relationship seems reasonable, a theory can be accepted in principle. However, it remains a theory, so it is still possible to do more experiments to try to disprove it. That is why people speak of the “theory of gravity” and the “theory of natural selection” while for almost all scientists these are accepted as “scientific fact.”

This leads to a natural confusion between what scientists and the public consider to be “facts.” Since theories are formulated in a manner which could theoretically be disproved, they cannot actually be “facts” as the concept is defined in the English language. Unlike mathematics, where one can prove that two plus two equals four, nothing ever gets “proved” in science. So there are no facts, as such, in science. That makes science an awkward tool, especially when countering critics who ask for proof. Even when providing overwhelming evidence, nothing is proved conclusively, the likelihood of finding evidence to the contrary merely diminishes.

While scientists are often good at their jobs of posing scientific hypotheses and testing them, they are not trained in communicating those results to the general public. Science, even in this modern era is often misunderstood and wrongly portrayed by the media, thus people in general have little idea of what science can and cannot do. This leads to the peculiar headlines of “Tomatoes Can Kill You,” or “Broccoli Cures Cancer” and subsequent rushes to toss tomatoes out or buy broccoli supplies, to the despair of children everywhere.

So what can science do, if it cannot come up with absolute proof? Science does experiments which can be described in numbers and probabilities. For example, a number derived from studies into the effects of smoking is that men who smoke are twenty-three times more likely to get lung cancer. Another number is that the average life expectancy of smokers is about seven years less than that of non-smokers. These numbers are based on very large sets of data, including studies of literally millions of people, so the theory that smoking is bad for your health is considered to be very reliable.

The statements that you get to hear in the media that broccoli and carrots are good for you and to stay away from red meat do not usually provide the numbers that underlie them. In order to understand the numbers and methodology, one needs to understand statistics.

Statistics is the mathematical study of the collection, organization and interpretation of numerical data. Statistics can be arranged in many different ways depending on how one quantifies things and then separates the numbers (do you include or exclude people who have an allergy to aspirin, and such). Since most people find these kinds of numbers extremely boring and can never stay awake long enough to read or listen to what it is all about even when they have to, it makes for a confusing world. Even so, one isn’t usually provided with the data itself by the general media, just a blanket statement of “fact.” Thus, most people don’t have the means to understand it. It doesn’t stop people from drawing conclusions based on media hearsay, however, which will be discussed further in the section on vaccine scares.

One important scientific hypothesis unknown in the world of the 1630s was the “germ theory.” It was still presumed in 1630 that “miasmas,” bad smells, caused disease. When the plague hit the countryside in Northern Italy around the town of Pistoia in 1631, the learned medical doctors were asked for their opinion as to what to do to prevent its spread. Their sole advice was a prohibition of silkworms and the production of raw silk in town. Since silkworms produce foul odors they were considered very suspicious. Plague is known in our time to be caused by a bacterium carried by fleas hopping a ride on rats. The town officials took much more drastic measures, and managed to keep the plague at bay through a very strict quarantine. When commercial interests conflicted and greed overcame fear, the increase in trade also increased the spread of the plague.

Bacteria are invisible to the naked eye, but can be seen with light microscopes. Anthony van Leeuwenhoek would extensively report on them by the 1670s. The connection between bacteria and disease was not made until much later. The question of where these little “animals” were coming from gave rise to two theories, spontaneous generation (germs materialize out of thin air) and the germ theory (germs make more germs). Pasteur concluded that the spontaneous generation idea was unlikely in the 1860s (note, we cannot not say disproved since we cannot prove a negative). He showed that sterilized media did not get bacteria or mold to grow in it, unless the bacteria or mold were introduced to it. Thus the germ theory became accepted. It was not until much later that overwhelming evidence was provided for the germ theory through the effort of many scientists in many different countries. This research culminated into Koch’s postulates.

Koch’s postulates, developed in the 1880s and 1890s, set forth an experimental framework for collecting evidence that a particular organism (pathogen) is responsible for a disease. The postulates (what the experimenter is attempting to “prove”) are:

1. The organism must be found in all animals suffering from the disease, but not in healthy animals.

2. The organism must be isolated from a diseased animal and grown in pure culture.

3. The cultured organism should cause disease when introduced into a healthy animal.

4. The organism must be re-isolated from the experimentally infected animal.

However, it is not in fact necessary to prove all four postulates to establish causality.

What are Pathogens?

Pathogens are endoparasites, that is, organisms which enter your body and adversely affect human health. They are the creatures, “bugs” or “germs,” that make you sick, and include both organisms invisible to the naked eye (viruses, bacteria, yeast and protozoa) and larger organisms (especially worms and insects). Other organisms are not pathogens themselves, but are important as disease vectors (they carry the pathogen from one host to another.

Pasteur, among others, hypothesized that germs caused disease. In the last century and a half, research has shown that for many diseases a bacterium could be isolated that was determined to be causative for the disease. Bacteria are small single-cell organisms that are all around us. A square inch of skin will have millions of bacteria on it. Bacteria are the most abundant organisms on the planet. The overwhelming percentage of bacteria are harmless to people and some are beneficial. A small percentage (less than one percent ) of different types of bacteria can be harmful.

Still, there were a number of different diseases such as smallpox, measles and rabies which seemed to be infectious diseases, but for which bacteria were never found to be the pathogen.

It was shown by Dmitri Iwanoski and Martinus Beijerinck in the 1890s that you could pass an extract of contaminated material through filters which could retain the smallest known bacteria, and you were left with a fluid which was still infectious in animals. The first scientists to show that filterable agents were connected with human disease were Landsteiner and Popper in 1909.

Later, using electron microscopes (first built in 1911) which can magnify objects much smaller than those detectable by light microscopes, viruses were found to be the pathogens responsible for many of the mystery diseases. Since electron microscopes won’t be feasible for some years, to some degree the down-time doctors are going to have to take statements about viruses on faith. That is, we can’t show them the viruses. However, we can show them that filterable agents carry disease.

Viruses lack some of the traditional attributes of organisms. Viruses cannot replicate themselves without infecting another cell. They reproduce, but need a host cell to do so. Likewise, they cannot metabolize on their own, and they lack a cell membrane. On the other hand, they engage in genetic transmission of information, and, like bacteria and protozoa, can cause contagious disease. Most viruses are harmless to human health because they lack the capacity to infect and survive in human cells.

Viruses consist of a protein shell which contains some genetic material. This can be either Ribonucleic acid (RNA) or Deoxyribonucleic acid (DNA). The individual building blocks, called nucleotides, of the DNA and RNA of viruses are chemically the same as the nucleotides of the DNA and RNA of our own cells. DNA and RNA are the carriers of genetic information; they describe the cell’s proteins by means of a particular sequence of nucleotides. The DNA remains in the nuclei, and acts as the master blueprint. Enzymes transcribe this information, synthesizing a “messenger” RNA equivalent which acts as the working copy of the instructions. The RNA passes into the cytoplasm, and there other enzymes assemble amino acids into the corresponding protein.

Viruses subvert the metabolic machinery of the infected cell, causing it to replicate the viral genetic material, express viral proteins, and assemble and export viral particles. The viral genetic material contains genes encoding, e.g., the viral coat proteins. The number of viral genes is usually small relative to that of a bacterium or protozoan.

A slight chemical difference between RNA and DNA makes RNA less resistant to physical and chemical attack. And because cells use a particular RNA transcript for just a short time, they are less likely to have elaborate enzymatic mechanisms for “proofreading” RNA. Hence, RNA viruses tend to have less genetic material, and that material is usually more prone to mutation. Since RNA viruses change more rapidly, they are harder to immunize against, and also more likely to “jump the species barrier.” That is, a bird influenza virus can become a human virus.

A parasitic disease is a disease caused or transmitted by an animal parasite. Malaria, amoebic dysentery, trichinosis, tapeworm infestations, and sleeping sickness are examples of parasitic diseases. Most parasitic diseases are no longer of much concern in the developed world since they are not very prevalent. In developing nations and in Europe of the 1630s, parasites are very common.

During the 1630s, there were many pathogens on the loose in the human population. Having an idea of the germ theory and thus knowing what is causing disease, allows the deployment of various effective means to fight disease. The first and foremost would be improvements in sanitation. As Ben Franklin said, “an ounce of prevention is worth a pound of cure.” Some of this may seem simple in principle, such as getting people to wash more frequently, boiling water prior to use as drinking water and not to dispose of human waste in the streets. However, it was not uncommon for people to wash the parts of their body which were visible in public. People washed their hands and face daily, and the relatively high number of drownings, beyond an inability to swim, may in part be attributed to their desire to wash in a river, canal or ditch. It is debatable whether that superficial cleansing would aid their general health when that same river, canal or ditch was also the main thoroughfare for sewage.

The progressive influence of the Ring of Fire would hopefully lead to improvements in sanitation by civil engineering projects to build sewage systems, clean drinking water supplies, and eventually, sewage treatment. Prior to that happening, making vaccinations to the more common and deadly diseases universal would make a major difference.

Vaccinations

What precisely is a vaccination? Vaccination (also called immunization) is the process of administering weakened or dead pathogens to a healthy person with the intent of conferring immunity against a targeted form of a pathogen. The weakened or dead pathogens will still have some of the features that live dangerous pathogens also have. These features, also known as antigens, are often distinctive of that pathogen, and thus can be used for identification, much as fingerprints are for people. If, when independently administered to a host, they still elicit an immune response—that is, activate the same body defenses as are activated when that antigen is presented by the original pathogen—they are called immunogens, and may be used in vaccines. In essence, vaccines cause the body to prepare against a pathogenic attack before it actually occurs.

When a person is given a vaccine, s/he will have an immune response against it, even though the weakened or killed pathogen is unlikely or unable to cause the disease. The immune system, over the course of two to three weeks, will develop cells (B-cells or more specifically called plasma cells) which produce antibodies against the antigens present in the vaccine.

Aside from B-cells, the human immune system has several other weapons to fight germs. There are a group of cells called T-cells which can be trained to recognize specific antigens similarly to B-cells. Instead of making antibodies, T-cells can directly bind in a lock-key manner with specific antigens. They can then ingest the antigens, and if the antigens are part of a virus or bacterium, swallow it whole and digest it. Beyond B-and T-cells, human cells make their own antibiotics, and have some cells, called natural killer cells, which behave as the computer game Pacman and just go out to gobble up anything that antibodies attach themselves to.

Microbial (including viral) pathogens can be weakened (attenuated), so they are less virulent to humans, by progressively adapting them to a new environment (a tissue culture) which is less like that of the human body. The advantage of attenuated vaccines is that they are very good in producing immunity. Unfortunately, they can still cause the disease (especially in individuals with weak immune systems), and they can evolve back into an non-attenuated form.

Pathogens can also be inactivated (killed) by physical or chemical methods. The advantage of the killed organism vaccine is that if the inactivation was complete—all of the organisms are dead—then there is no chance of contracting the disease as a result of the immunization. (Of course, if you miss some, then you are exposed to the fully virulent beastie.) The disadvantage is that the killed organism may be only weakly immunogenic.

How does vaccination make a difference in human health? Apart from enabling individual people to survive otherwise deadly diseases, once enough people in a community have been immunized, that community as a whole will also have resistance to the disease. This is called “herd immunity.” Depending on the disease virulence, i.e. how easily it can spread from person to person, herd immunity can protect even those individuals in the community who are not immunized because there is no one in their surroundings who can spread the disease to them. This can have a very significant impact on infant mortality.

How difficult is it to create a vaccine? For that question, we first need to take a step back in history and see how vaccines used to be made. Second, we can use modern knowledge and experience to ensure that any new vaccines made in the Ring of Fire world would be safer and more effective than those that were tested and developed early in our own history.

Historical vaccines

Normally, when we get infected with a pathogen, we get sick. If it doesn’t kill us we build up immunity which provides us with a very good defense against that disease should we encounter it again. However, this defense doesn’t necessarily last a lifetime. Depending on the disease, protection can be for as little as a few months. This is because the human body can build immune defenses for the short, medium and long haul. For some reason, which modern medicine is still trying to determine today, we get some diseases and our immune system forgets we ever had them. Even immunization against them is relatively ineffective. Usually we don’t even try. We merely provide relief for the symptoms and fight the disease with other medicines. Most diseases, however, elicit a longer term immune response. Some immunizations do last a lifetime. In the modern world we generally receive many shots while we are children that are meant to provide lifetime protection.

The first reports of vaccination appear in the western literature in the beginning of the 1700s. This involved collecting a pustule (pock) from a patient who had a mild case of smallpox and applying the pus extracted directly into an open wound on the leg or arm of a person wishing to be immunized against smallpox. This practice, initially called grafting or inoculation, came to be known as variolation. It should be noted that, outside the Western world, no wound was made to apply the pus to. A minimal drop was placed on the skin and the location was merely scratched with a blunt needle, very similar to how vaccinia is still provided today. The “learned” doctors again had to “improve” on the matter by preparing their patients by bloodletting, purges and other nasty ways of making a person suffer prior to making deep incisions and placing in large quantities of pus. This caused much more severe disease and even outright smallpox among their victims. The last royal Briton to die of the disease was the four-year-old son of George III in 1783. His father had survived the disease, but his son didn’t survive the doctor’s inoculation.

These first reports of variolation at the London Royal Society are derived from two foreign fellows of that society who had observed the technique in the Ottoman Empire. The medical establishment was rather disdainful of the technique, but it had the support of Lady Mary Wortley Montagu, the wife of Britain’s ambassador to the Ottoman Empire.

It should be noted that variolation has a much longer history in many parts of the world. It was a prevalent technique used in Africa and the Ottoman Empire as well as in China and India. The thought behind the practice was simple: if someone had a mild case of smallpox, transfer it to someone else and they would have a mild case themselves. The reality was somewhat different. Smallpox can be highly lethal, with around a thirty-percent mortality rate for those who catch it from others. Almost everyone who recovered was seriously scarred. In men, infertility after smallpox was common. It normally was transmitted through person-to-person contact but could also be transferred by air.

The smallpox virus present in a ripe pustule was mostly dead, in that it generally consisted of fluid containing partially destroyed virus particles surrounded by active immune cells already fighting the virus. This, as well as the indeterminate amount of time between harvest of the pustule and infecting a healthy individual on the skin, allowed for a greatly weakened infection. The patient would get a large pustule at the site(s) of incision. After a period of about eight days, a fever would appear as well as small red marks (on average between ten and one hundred) on various parts of the body, most close to the site of variolation. The fever would usually break within two days and the marks would develop to small distinct smallpox pustules, which would mature and heal without leaving a distinct scar in the two weeks that followed.

Variolation was also performed in the British Isles and was happening right under the noses of the learned MDs and they never even noticed. It was practiced by lay physicians and midwives in the countryside and was passed along in various rural communities.

Smallpox was a constant major killer in Western Europe in the early modern period that Grantville landed in. It was a childhood disease in that people tended to catch the disease before the age of five. Of children below the age of five who did get it, about forty percent died. Adults, while also vulnerable, had a much better chance of survival. Variolation increased life expectancy in England by about ten years—a large jump. No major reported vaccination of another disease took place in the 1700s. Under influence by a campaign started by Jenner, variolation was phased out in the Western world in the 1840s and replaced with vaccinations of cowpox instead. Cowpox is a virus related to smallpox but has adapted to infect cows. Because the virus is more at home in cows, it doesn’t tend to make people ill when given as a vaccination, but because it is related to smallpox it does prepare the immune system of those vaccinated with cowpox for infection with smallpox.

To go into additional vaccine development, it is necessary to mention Pasteur again, as he is credited with the discovery of immunology. This is the science that describes the process by which our bodies defend ourselves against pathogens. His discoveries consisted of making weakened strains of several diseases, anthrax and rabies among them, and using these to immunize cattle and people. In honor of Jenner, who had coined the term “vaccine” for the immunization of people against smallpox using cowpox, Pasteur coined the term “vaccines” to generally denote artificially weakened strains of pathogens used for immunizations. His first vaccine, for chicken cholera, was made by accident. His assistant, Charles Chamberland, was supposed to inject some chickens prior to vacation, but did not. When he returned a month later, Chamberland proceeded to inject the chickens with the month-old culture. Instead of coming down with the deadly disease, the chickens were only mildly ill. Re-challenging these chickens with a fresh culture of chicken cholera did not cause disease in these chickens because they had been immunized. Pasteur laid the connection between using a weakened or dead pathogen and achieving immunity without disease.

Today some vaccines are still made from weakened or dead pathogens. This process is highly regulated by health authorities such as the American FDA. It has a very high profile because of the vaccine scares among the public in the past few decades. However, there are newer vaccines which don’t use a whole organism at all. Instead, they are what are called subunit vaccines. These can be fairly crude (e.g., the membrane, or protein, or polysaccharide fraction of the killed organism) or highly characterized (e.g., a particular immunogenic protein made by recombinant DNA techniques). The design and manufacture of subunit vaccines won’t be possible in the immediate post-RoF era.

Vaccine Scares

In the past decades there have been two vaccine scares which have kept people from using vaccines, first in the 1970–80s with DTP vaccine (diphtheria, tetanus, and pertussis) second in the 1980–90s with MMR (measles, mumps and rubella). In each case, the media failed to grasp the relative danger of the vaccine compared to the damage that the disease causes. What people clamor for is proof of safety. Misunderstanding of how science or the immune system works causes problems. The scientists either fail to explain these correctly, or more likely, the media fail to report them correctly. While science cannot offer one hundred percent safety, it can provide percentages. These numbers have been able to overwhelmingly describe the safety of vaccines.

Doctors and nurses, including those in Grantville, are acutely aware of the power of vaccines in the prevention of disease in individuals and the ability of vaccines to provide herd immunity for the community. They would have to be certain to explain the “facts” of how vaccines work very clearly, once they are in the 1630s.

Vaccines work by stimulating the immune system, the full process of which can take three or four weeks for a first immunization. Should someone already have a disease, and they are vaccinated after getting infected, the vaccine will not help them. There are many people nowadays who still believe that getting a flu shot actually gives them the flu. Personally, I have heard claims of people saying that they had a case of the flu within a week of vaccination. Considering that most people call any kind of sniffle the “flu”, and how common the common cold is, I know what I suspect rather than the flu shot.

People from Grantville will have to be very clear in how they describe what vaccinations do and how they work. With exception of the rabies vaccine, vaccines can only work preventively. Thus if they go into a community, vaccinate against diphtheria, and the very next day people are already dying of it, they were too late for those people who had already contracted the disease. When people die, responses are often not rational and reasons are sought. In the world of the 1630s, in Europe, the hand of God was seen everywhere by many people. Given irrational responses the world wide throughout history against vaccinations, any vaccination program initiated by Grantville would have to be a program of information at least as much as medicine.

Grantville has arrived in the 1630s . . . now what?

Grantville is in luck. Aside from having two active doctors, eleven registered nurses, and a confusing number of EMTs, they also have three retired MDs. In addition, among the first people they run into is Balthazar Abrabanel, a Jewish court doctor, although he was suffering from a heart attack at the beginning of the tale. By the time the town meeting at the high school’s gymnasium was called, Grantville had been in 1631 for three days.

One of the aspects not discussed in the subsequent chapter is what James Nichols as head of the “Medical and Sanitation Committee” would be setting out to do. I would very much assume that he and the committee would be extremely busy. We have assumed that Grantville was lucky, and among the refugees to pass by them in the first few days there were none with plague, typhoid, cholera, smallpox or any other deadly debilitating disease. Were they not to have been so lucky, the 1632 history line would be somewhat more depressing, since a large percentage of people described in the stories would never have made it. Many diseases could have been controlled by forcing improved sanitation on the part of down-timers (as described in part in 1632), in addition to quarantining people with disease. Many other aspects of modern know-how on sanitation, the rapid development of one or some of the antibiotics, such as Chloramphenicol and knowledge of epidemiology would allow for rapid responses to health care crisis. The prevention of large scale outbreaks of disease is one of the means that the committee would respond. For example, developing means to prevent a smallpox outbreak among the up-timers would have had to be dealt with immediately.

Smallpox

A description of the Boston smallpox epidemic of 1721 may serve as an example of what Grantville could expect should it not take action. In 1721, Boston had been free of smallpox since the epidemic of 1702. Boston had a strict quarantine rule for incoming ships. Each incoming ship was inspected for the presence of disease. If any member of the crew showed symptoms of disease, the ship was anchored next to Spectacle Island, at the far end of the harbor. Spectacle Island had a hospital where sick crew members could be treated. No member of the crew was allowed ashore in Boston until three weeks after everyone was symptom free. This method was effective. The previous October, a ship coming in from London flew the yellow flag, indicating disease on board. The ship only had eight people on board who had not had the disease. By the time they reached Boston harbor, seven had come down with it. They were fortunate in that only one had died and had been buried at sea. The last person who had not shown signs of the disease until reaching the harbor was Captain John Gore, a Boston native. Three days later he came down with the disease and a week later he died. By staying out of town, choosing not to see his wife a last time, he saved the city from a smallpox epidemic.

The next year Boston was not to be so lucky. When a large fleet came in from the Caribbean, ships were processed as usual by the harbor authorities. They were cautious since there were smallpox epidemics ongoing in both London and Barbados. There was one oversight in the regulations. It didn’t apply to naval vessels. The captain of the Seahorse, the Royal Navy escort frigate for this convoy, was much more interested in claiming prizes and capturing pirates than he was in health. He failed to report, and claimed ignorance of, widespread smallpox among his crew. He instead claimed he suffered from “massive desertion.” Within weeks Boston, a city of about 11,000 people, started to suffer from a smallpox epidemic. In the end, there would be 5,759 cases of which 848 died.

When, during this epidemic, a Boston lay physician, Zabdiel Boylston, who had been trained first by a Dr. Cutler in Boston and later as an apothecary in London, started using the practice of variolation, he met with fierce resistance from the official medical establishment in the city. As Dr. Cutler’s assistant, he had seen the vast devastation that smallpox left behind in the community before catching it himself and having to fight for his life in 1702. He helped variolate 287 people during the 1721 epidemic, among which were his own children. The opposition was so fierce that he was nearly arrested, crowds were instigated against him and he came close to being lynched. Of the variolated people, six died, most likely due to having caught wild smallpox prior to variolation. Boston was particularly vulnerable to a smallpox epidemic because so many of its citizens had not had the disease. Grantville may be in even greater danger.

But one could say “so many people have been vaccinated in Grantville, why would smallpox harm those?” The answer is two-fold. First, all routine vaccination with vaccinia stopped in 1972 in the USA. The most recent people to be vaccinated would have been members of the US armed forces where the practice was stopped in 1990. Most people born after 1972 are unvaccinated, thus herd immunity would be very low.

A second complication is that vaccinia does not necessarily provide lifelong or complete protection against smallpox. This is unlike survival of actual smallpox which does confer lifelong protection. So Grantville’s population lacks herd immunity to smallpox.

This is literally asking the “speckled monster” to strike. Smallpox in Western Europe in the early modern era was endemic (around all the time). People very rarely had a chance of living their lives without encountering it. Among the refugees, camp followers, armies or cities nearby, there would be active smallpox. It would be only a short time before Grantville would come into contact with smallpox, and this would call for a drastic response.

Dr. Nichols was present at the shootout with the mercenaries at the farm right outside the Ring of Fire on the first day. He would not have failed to notice that among the dead mercenaries half or more of them would have shown the telltale signs of smallpox survivors. The question would be whether he and the other medical experts from Grantville would know and realize the lack of herd immunity to smallpox. It is very likely that they would. Would they also know that a booster would be the better gamble than to count on thirty-year or older immunization? Again, it is very likely that they would. They would certainly know that the half of the population born after 1972 has no immunity whatsoever.

Grantville will not have any supply of vaccinia. It is unlikely that any cow present in Grantville will have cowpox, and horsepox, also known as “grease,” was as extinct as smallpox in the time Grantville came from. That means the source material for the vaccine must come from down-time territory. What source material would they go for? It is unlikely that any of the up-timers have much background in making vaccines. They would have textbooks and perhaps some more detailed medical articles from Doc Adams or one of the retired doctor’s archives, but none would likely provide a precise description of how to formulate such a vaccine from source material.

The question becomes whether to formulate the vaccine at all or take a more primitive approach. Here, Balthazar Abrabanel may be helpful. He may very well have known about variolation (inoculation with attenuated smallpox), and may even have practiced it, considering his contacts in the Ottoman Empire. Among the up-timers, there would be some knowledge of variolation.

Modern knowledge about the germ theory could make variolation a relatively safe option, with two possible careful modifications. One modification would be to take the source material, fluid/pus from a smallpox pustule, and to lightly heat it (at 60º C for an hour would do), thus further inactivating it. This is possible with the available technology. The heat-treated viral material, would likely still be capable of inducing immunity, but would not be as likely as the traditional variolation material to spread live smallpox or to induce the other possible complications seen with variolation. As it would be a mostly disabled virus, all members of the community could be variolated.

This would be started with those members of the community who had most recently been vaccinated. These would also be the people who would have to be used to greet incoming refugees and screen them for possible quarantine purposes. One advantage would be that by variolating these previously vaccinated people, their blood will be rich in antibodies to smallpox after the variolation. They could donate a pint or less of blood and their plasma would serve to protect those few people who may come down with complications or show signs that they may become more ill with smallpox. This form of passive immunotherapy is called an enriched immunoglobulin. In this case the blood donated is enriched for antibodies/immunity against smallpox. Giving this plasma will provide people with some immunity against smallpox that will last for about one month. Smallpox elicits a stronger immune response than cowpox. While cowpox immunity may not last or offer complete protection, smallpox immunity does. A single variolation would be sufficient for a lifetime and the up-timers and their children will need it.

Should Grantville be so lucky that smallpox is not present in their area of Germany at the time that they landed, they are provided with an additional option. The technology required to vaccinate or variolate the Grantville population is very minimal. Given their knowledge of vaccination they could go out and look for cowpox or grease and provide people with a primitive vaccination based on these pathogens. Another source, possibly known to the veterinarians of Grantville, would be the cats of the Netherlands. Cowpox and grease are viruses closely related to smallpox virus that are adapted to organisms other than people. While people can be immunized with these viruses, the chances of becoming seriously ill are much lower than with smallpox virus. If they should follow such an inoculation by variolation, the whole population could be safeguarded at a relative minimum level of risk.

So Grantville has fought its first major enemy and won an overwhelming victory. It has defeated the greatest scourge in the history of mankind. They took a risk, and decided to go with the aggressive, but in the end safest, route and everyone in the community has been variolated aside from the youngest babies who will undergo the procedure by age two. Herd immunity should function to keep those little ones safe to begin with. A procedure has been set in place to continue the practice on incoming refugees to keep it that way. This would involve a quarantine for the set period (about two to three weeks) while they are building up their immunity.

After beating smallpox, the medical professionals of Grantville can congratulate themselves and after a great sigh of relief start to lose sleep again over the many other diseases they face.

Plague and other nasty bacteria vaccines

Herd immunity in Grantville will be very high to those diseases we in the modern era are almost all immunized against. Measles, mumps, rubella, polio, pertussis, tetanus and diphtheria would not be a problem to start with. But diseases which currently are virtual unknowns in the developed world, such as typhus and plague, will find up-timers fertile ground if ways to protect them are not designed. Even with quarantines, eventually one or another of these diseases will hit. Making antibiotics would be trying to cure the disease after it hits and there will be plenty of cases where up-timers will need those drugs when they won’t even know what is hitting them. But for several well-known diseases it would be possible to make whole-cell vaccines and provide immunity. These whole-cell vaccines would be less safe than current vaccines and would likely have more side effects, but they would work. From a community perspective, the safety they would provide would by far override the side effects, such as fever or sore arm at the injection site.

Using very basic bacteriology techniques, presented in any introductory bacteriology book, the bacteria causing the most dangerous diseases could be isolated, verified and grown. Many of these diseases have very clear symptoms. Samples can be taken from carriers of the diseases among the refugees or from the nearby towns. In these samples, the bacterium causing the disease would be present. These will be grown, isolated and a single type of bacterium selected. This bacterium would have characteristics similar to those described in the medical textbooks as to what the disease bacterium looks like. Finally, however horrible it may sound, it would be used to infect healthy animals, likely mice or rats. (This is an application of Koch’s postulates.)

Once it is verified that this bacterium does cause the disease, it can be prepared for the vaccine. These bacteria can be grown in a large batch, isolated and heat-killed. It is easy to verify whether or not any bacteria survived. These “dead” bacteria are tested to see if they are truly dead by growing them. It is then tried out on another batch of animals. If the animals get sick, go back and repeat the process. If the animals don’t get sick, the animals will then be challenged with the real live bacterium and see if they now survive. Once the effectiveness is ascertained, these dead whole-cell bacteria can be used for vaccinations.

There are reasons why using these whole dead bacteria cell vaccines would work. Bacteria have special components on their cell walls. These are related to the sugar people put in their coffee or tea but are chemically a bit different. Our immune system can tell this difference and responds very strongly when exposed to these kinds of sugars. That is why these whole cell vaccines would be able to provide very good protection. Standard vaccinations against plague, typhoid, and typhus would seem entirely obvious. These are especially necessary for people who need to dwell away from Grantville in large cities such as Amsterdam, Venice, Rome, Paris and London.

“Normal” vaccines

How would the Ring of Fire world go about regenerating the vaccines we are using currently? Would it be necessary? Would it be possible and what would it take?

Measles is a disease virtually everyone would get as a child prior to the vaccine against it. It kills about one in a thousand infected children. The symptoms begin with a cough, a rash, runny nose and fever. It often progresses to severe dehydration and five percent of children get pneumonia. The measles vaccine is given as a combination shot with mumps and rubella (German measles). Measles at the time of the Romans was a much more virulent disease and was known to kill at a similar rate to smallpox. People have either adapted or it has adapted to people to be more “benign.”

Measles, polio, mumps, rubella and varicella (chickenpox) vaccines all consist of weakened viruses created in the lab. The easy option would be to save some of the vials that Doc Adams likely has and use it as a starter to culture these weakened viruses. Otherwise, to make the vaccines, a sample needs to be taken from the throat of an infected child, cultured in tissue culture in the lab in human or animal cells; historically this was done in chicken embryo cells or human embryonic connective tissue cells.

In the Ring of Fire universe, it may be a while before tissue culture (sterile growing of cells in petri dishes) that could produce these weakened virus strains will be possible. But when it does become possible, a very similar route will lead to a very similar result. By culturing these viruses in tissue culture, they become adapted to living under those conditions. Only those viruses which adapt, literally change their genetic blueprints to function better in tissue culture, will survive. When this is done to generation after generation of viruses, the viruses lose their ability to replicate and survive well in people. They are then ready to function as much weakened sparing partners for the children’s immune systems to train themselves on. Given the effort and up-timer knowledge, making these vaccines in a crude form would be feasible within five to ten years of the Ring of Fire.

Hib (Haeamophilus InfluenzaeB), MenC (Neisseria meningitidis) and pneumococcal vaccines are against three different bacteria which cause either encephalitis or meningitis. The vaccines for these diseases may be among the hardest to reproduce. They are made by linking the special sugar groups which the pathogens have in their cell walls to a carrier protein. This combination allows children under the age of two to make, and to continue making, active antibodies against these sugars, which children are not able to do without the carrier protein. There is, however, a possibility of using a whole-cell vaccine again. Whether this would work well enough for the under-two age group is a question they would have to determine the answer to themselves.

DTaP (Diphtheria, Tetanus and acellular Pertussis vaccine) is a difficult case. This is actually a trivalent vaccine, that is, one which protects against three different pathogens by providing corresponding immunogens. The simple aspect would be to create a whole-cell pertussis vaccine. The tougher parts are tetanus and diphtheria. In both tetanus and diphtheria, the bacteria are not targeted, but rather the toxins these bacteria produce. It is the toxins which even in minute quantities damage human cells or nerves and can kill when these bacteria infect people. Usually these bacteria have trouble growing in people because we use oxygen and it is present in our tissues. Both of these two bacteria species are obligate anaerobic bacteria, meaning that they live only under conditions without oxygen. That would make it difficult to culture them without developing some equipment for it first. If that gets done, making the vaccine is relatively easy. The toxins are produced by the bacteria and expelled into the media they are grown in. The bacteria can be filtered out, the toxin inactivated by formaldehyde and the toxoid (inactivated toxin) concentrated. This would be very dangerous because these toxins are extremely deadly.

Other Vaccines

Making a rabies vaccine in a crude form similar to that of Pasteur is not very difficult. It involves infecting a rabbit, letting it get sick and then killing it, extracting the spinal cord, and letting it dry. The drying kills the virus and then bits of this can be injected many times over many days.

The flu vaccine, on the other hand, would be very difficult to produce. It is likely they would choose to go for more readily available and more likely targets first because it requires much more infrastructure to make effective flu vaccines.

Tuberculosis is a major killer. In 1632, it killed three times as many people in London than did smallpox. The current vaccine for tuberculosis is not used in the U.S.A. or Holland, but is employed virtually everywhere else and has been used since 1921. It does not appear to prevent tuberculosis in people but it prevents the most deadly form of the disease in young children about eighty percent of the time. This vaccine is made from bovine (cow) tuberculosis bacterium. When it was originally made by Calmette and Guérin, they weakened this bacterium by continuously culturing it in the lab for thirteen years.

Conclusions

Would people from Grantville use vaccines now that they are back in the 1630s? Personally, I can’t see how they couldn’t. It would go with their spirit to go out and try to conquer these diseases just as much as they set out to make themselves and their neighbors safe from Tilly’s mercenaries. They are already armed with much knowledge: of the scientific method, the germ theory, statistics, epidemiology and even the nature of the enemies they are fighting. They would have it in their own hands. It is a choice to make between living in fear or actively fighting the demon who feeds that fear. Would the vaccines they would develop be as safe as they are now? Not likely. There is just so much less testing that could be possible with what they have. It is very likely that in this process there will be mistakes made and lives lost. But overall, the tally will be so many lives saved, not just in Grantville, but wherever they manage to teach that dying of certain diseases is a choice, not a certainty.

References

The Dutch Republic, Jonathan Israel. Oxford University press. 1995.

Introduction to Bacteria: for students of biology, biotechnology & medicine, Paul Singleton. Chichester; New York: Wiley, 1992. 2nd ed.

When Plague Strikes: the Black Death, Smallpox, AIDS, James Cross Giblin, New York: HarperCollins, 1995.

The Speckled Monster: a historical tale of battling smallpox, Jennifer Lee Carrell. New York: Dutton, 2003.

Vaccines: What You Should Know, Paul A. Offit and Louis M. Bell. New York: Chichester: Wiley, 2003.3rd ed.

Health, Disease and Society in Europe, 1500-1800; A source book, Peter Elmer and Ole Peter Grell eds. Manchester University Press, 2004.

The Conquest of Smallpox, Peter Razzell. Caliban books 1st ed. 1977. 2nd ed. 2003

Online Resources

http://www2.sunysuffolk.edu/westn/people.html, life of the people in the early modern era

http://en.wikipedia.org/wiki/Scientific_method

http://en.wikipedia.org/wiki/Louis_Pasteur http://www.sciencemag.org/cgi/content/summary/291/5512/2323
http://www.medicalnewstoday.com/medicalnews.php?newsid=47385 http://www.sciencemag.org/cgi/content/summary/291/5512/2323, UK vaccination schedule

http://www.dur.ac.uk/anthropology.journal/vol13/iss1/casiday/casiday.html, http://www.cdc.gov/NIP/vacsafe/research/lancet.htm
http://www.geocities.com/issues_in_immunization/fearmongers/opposition_to_immunization.htm vaccine scares in the 20th century.

http://www.lrb.co.uk/v26/n13/penn01_.html, fraud and media in causing disruptions in vaccine coverage

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About Vincent Coljee

I am from 1967, a good year if I say so myself. I am Dutch-Canadian, happily married to a wonderful English lady. I only first came across the 1632 book in early 2006 and played catch-up until the end of 2007 when other things came in between me and this particular hobby. My interests in history and science stem from a very young age, and have been going strong since. I have built up a fairly substantial science fiction collection over my lifetime and have been known to attempt to devour libraries in my pre-parent days. I am finding alternative history is my favorite, although I certainly also stray back to the hard science fiction fold since alternative history is still pretty thin on the ground, although there are new authors breaking in now more regularly.

Professionally, my training was in the USA, with a chemistry degree in college and a PhD in biochemistry and biomedical nutrition completed in Philadelphia, followed by a post-doc in Boston. I did a five year stint in Denmark at a Danish biotechnology company in the early 2000’s (that’s how I ended up missing out on 1632 for so long). Following that, I spent some time at Harvard while setting up a biotech company with a friend. That way I became the Chief Scientific Officer of a biotech company until the end of 2012, something that took a lot of time away from reading and writing fun things, but certainly was exciting. I am currently back working at Harvard University, researching the biophysical secrets of DNA and DNA protein interactions.

I have two kids, boy who is a chip of the old block, and a lovely young lady who is taking after my dear wife (lucky for her). I will likely remain focused on science/medical related fiction and especially non-fiction. I am a proud dyslexic, have worked hard to become who I am despite people’s believes. I am a firm adherent of the scientific method even in my own life, it is whatever works (within reason and ethics). For those other dyslexics out there, take heart, we don’t all need to be like Edison, Ford, Agatha Cristie or even Einstein. ;o)
Previously published works by Vincent W. Coljee are:

“Herd Immunity,” Grantville Gazette , Volume 10

“A Gift of Blankets,” Grantville Gazette , Volume 11, co-written by Kerryn Offord. Please see the entry under both names to read the story.