The Grantville Gazette - Vol. 10 Part 38

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 dest.i.tute 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 pract.i.tioners.

The tale of Madame Louise Bourgeois shows how much power the MDs had and how willing they were to use it against women pract.i.tioners, 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 ma.s.sive 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 pa.s.sed 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 a.s.sumptions of some kind and some of these a.s.sumptions 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, doesnot 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 ofPistoia 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 lice 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 pa.s.s 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 sh.e.l.l 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 pa.s.ses into the cytoplasm, and there other enzymes a.s.semble 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 a.s.semble 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 p.r.o.ne 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 inEurope 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, ca.n.a.l or ditch. It is debatable whether that superficial cleansing would aid their general health when that same river, ca.n.a.l 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 quant.i.ties 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 theOttoman Empire . The medical establishment was rather disdainful of the technique, but it had the support of Lady Mary Wortley Montagu, the wife ofBritain 's amba.s.sador to theOttoman 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 inChina andIndia . The thought behind the practice was simple: if someonehad 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 theBritish 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 pa.s.sed along in various rural communities.

Smallpox was a constant major killer inWestern 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 inEngland 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 a.s.sistant, 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 197080s with DTP vaccine (diphtheria, teta.n.u.s, and pertussis) second in the 198090s 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, inEurope , the hand of G.o.d 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 a.s.sume that he and the committee would be extremely busy. We have a.s.sumed that Grantville was lucky, and among the refugees to pa.s.s 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 theBoston 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 anch.o.r.ed next toSpectacleIsland , at the far end of the harbor.SpectacleIsland had a hospital where sick crew members could be treated. No member of the crew was allowed ash.o.r.e inBoston until three weeks after everyone was symptom free. This method was effective. The previous October, a ship coming in fromLondon 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 reachedBoston 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, aBoston 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 yearBoston was not to be so lucky. When a large fleet came in from theCaribbean , ships were processed as usual by the harbor authorities. They were cautious since there were smallpox epidemics ongoing in bothLondon andBarbados . 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 "ma.s.sive desertion." Within weeksBoston , 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, aBoston lay physician, Zabdiel Boylston, who had been trained first by a Dr. Cutler inBoston and later as an apothecary inLondon , started using the practice of variolation, he met with fierce resistance from the official medical establishment in the city. As Dr. Cutler's a.s.sistant, 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 theUSA .

The most recent people to be vaccinated would have been members of theUS 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 inWestern 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 theOttoman 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 60 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 pa.s.sive 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 ofGermany 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.