Grantville Gazette, Volume X Read online

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

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

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

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

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

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

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

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

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

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

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

  One important scientific hypothesis unknown in the world of the 1630s was the "germ theory." It was still presumed in 1630 that "miasmas," bad smells, caused disease. When the plague hit the countryside in Northern Italy around the town of Pistoia in 1631, the learned medical doctors were asked for their opinion as to what to do to prevent its spread. Their sole advice was a prohibition of silkworms and the production of raw silk in town. Since silkworms produce foul odors they were considered very suspicious. Plague is known in our time to be caused by a bacterium carried by 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 d
iseases 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.