Grantville Gazette, Volume X

by Eric Flint

  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. Asid
e 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 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 the
y 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.