1632

by Eric Flint

  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:

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

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

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

  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.