by Eric Flint
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 Influenzae B), 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.