In 542 Constantinople, a city which imported all of its grain, lost 10,000 people a day for months to plague. The population of Europe was reduced by 50% from 550 to 700CE, and again in the 1330s it struck Asia and reached epidemic stage in Europe in 1347.

In the late 1300s the plague killed one European in three; some estimates place the deaths at closer to 50%. Thousands of people a day were dying, there was no one to pick up bodies or console the horrible and agonizing sick. Whole villages were inhabited only by the dead. So many Europeans were killed that the forests returned and the wolf and the bear were plentiful again. It took 250 years for the human population in Europe to recover from the first epidemic.

The plague is still around and is detected occasionally in rodents in the Sierras.

Bubonic plague kills horribly if not treated. Lymph glands swell and burst, the skin turns black, death is a relief.

There have been other plagues, or epidemics, such as the plague of small pox and measles which Europeans brought to the Americas, killing so many people whole empires fell. It was the filthy hygienic habits of the Europeans, and not simply the superior weapon of the musket, which won America. Yellow fever, a "hemorraghic fever," killed several hundred thousand people in Europe in the 19^th century, including half the French army invading Haiti. Typhus was a common epidemic and killed many during the civil war; it is carried by lice and fleas.

The "Spanish flu" outbreak of 1918-1919 killed between 50 and 100 million people in two years. Like most "flu" bugs, it began with sniffles and from there some people had a cough and some people died from fluid filled lungs. The current Swine Flu outbreak in Mexico and elsewhere is of that type of flu.

Non-killer epidemics
Diseases that have "plagued" mankind endemically, meaning some infections all the time, are common. Chlamydia is nearly epidemic; it is a bacteria and is transmitted sexually. About 2.3 million Americans are assumed to have Chlamydia, which displays few symptoms but can have potentially devastating consequences including sterility and arthritis.

Norovirus, a virus the spreads readily from person to person contact and on food is probably also nearly epidemic. It gives most people a "24 hour" intestinal bug; there are several strains and it evolves quickly, and immunity doesn’t last long. It is estimated that some people in nursing homes or day care get noro ten to twelve times a year, sometimes only feeling a little "down".

A very serious and very common threat is methicillin-resistant Staphylococcus Aureus, known as MRSA. MRSA effects the skin and soft tissue, manifesting in sores that simply won’t go away, or can spread. It can also infect the lungs with devastating results.

If the staph bacteria should find a significant advantage, or if a mutation should occur, it is possible the disease could become radically more virulent. It is a very difficult disease to cure, though currently only about 5000 people a year die from MRSA. A more virulent MRSA would be very scary indeed.

HIV/AIDS is epidemic in many places in the world. In the U.S. drugs have made HIV/AIDS much more survivable, but with typical adroitness, the virus mutates quickly, making it difficult to stay on top of the disease. There are about 50 million related deaths each year.

To prepare for a coming plague, we need to understand what makes a "successful" terrifying epidemic infection.

• First, a method of transmission that is rapid and sure;
• Next, some novel feature which makes it hard for drug companies to respond;
• The ability to kill readily;
• And finally, the ability to "evolve" quickly.

Lines of Transmission
Water is a very popular way for plague to spread, and waterborne illnesses are currently widespread, and will become more common as earth dries, fresh water sources are polluted, and people are forced to drink unsanitary water. Common are bacterial and protozoal diarrhea, hepatitis A, and typhoid fever.

Malaria continues to "plague" some 350-500 million people a year with 1-3 million deaths, and drug resistant strains are emerging. The mosquito is a very efficient vector for disease.

For the bubonic plague, fleas were the vectors, and direct person to person transmission was possible but less likely. If there were no fleas, the plague would not have had nearly the impact it did. It was not widely understood until nearly 1900 that fleas were the vector for the disease.

Flu is dangerous because it spreads readily, in the air mostly but also person to person and surface to person.

Indeed, person to person is the most difficult epidemic to treat, because there is no vector to control, no mosquitoes to kill, no fleas to dust. People have to breathe.

In designing the perfect plague, we’ll choose "person to person" as the means of transmission. This is most effective because people travel all over the world, one can catch a disease in one country and spread it the next day half a world away. The Severe Acute Respiratory Syndrome (SARS) outbreak of 2002-2003 is a good example of how quickly a disease can go from an obscure province in China to 37 countries in just a few weeks. Human to human is definitely our choice for transmission.

Something new
For our next characteristic, something novel, there are a couple of choices. Viruses that come from animals are particularly hard to deal with, hence "Swine Flu" and "Avian Flu". Most of our deadly diseases started in animals and took advantage of humans because of our close association with the animals we eat. Viruses in general are very hard to "treat". A virus that would move readily from animals to humans and then humans to humans would be ideal for a pandemic. Swine flu is such a virus. However, several bacteria have recently developed some new tricks, and they are currently contenders for the next big pandemic.

Deadly
The ability to kill readily is a key to a really terrible epidemic. As we have seen, norovirus could be considered a pandemic, but the only effect is mild illness. Mild discomfort doesn’t close cities and bring down empires.

Several likely pandemic candidates can kill.

Flu, of course, kills, indeed, the better your immune system works, the more likely it is to kill. But, there are other contenders.

Fast Forward
Finally, the ability to mutate or evolve quickly. This feature makes for a nearly unstoppable infectious threat. Viruses multiply very quickly, and can change within hours. Bacteria, on the other hand, can "learn" from each other. Many diseases fit this description of "rapidly evolving", partly because their life-cycles are so rapid. Bacteria and viruses both reproduce incredibly quickly under the right circumstances.

This is important because our response, whether the immune system in our body, or the "extended" immune system of medical science, responds to the invaders, and the faster they can change, the harder it is for us to keep up.

 Virus?
What is the difference between a virus and a bacterium? Most of us remember our 8^th grade biology class enough to recall that a virus is simply genetic material packed in a protein envelope. All viruses are parasites. They don’t produce waste and don’t really use energy. A virus does one thing: reproduce, and it can’t do this alone, it doesn’t have enough moving parts. It has to find a host, invade the cell of that host, and inject its genetic material. The material then hijacks the cell’s genetic material causing it to make more viruses.

Viruses are probably the most common "thing" on earth, outnumbering even the numberless bacteria.

Interestingly, though most people consider viruses to be only destructive, that might not be true. Viruses bring chains of RNA and DNA to their host. It is possible that, in their role as parasite, they actually promote "evolution" by moving RNA and DNA between hosts. Interesting article HERE.  In addition, some viruses only attack specific bacteria, and others attack mostly tumors. Some day a virus might be used instead of surgery, or in place of our rapidly ineffective antibiotics.

Mostly, however, viruses are parasites, so simple that some people argue viruses are not alive, they are simply chemical machines. Some viruses can remain dormant, just little dry bags of genetic material, for hundreds of years. Just as bacteria are gaining a resistance to antibiotics, viruses are becoming resistant to anti-virus drugs.

Though bacteria reproduce rapidly, most every 10-16 hours, they do not reproduce as rapidly as viruses. However, bacteria have a neat trick. Though they typically reproduce "asexually" by budding a new clone, they also "exchange" genetic materials with other bacteria of the same or even different species. Here’s one downside for us: the E. coli living in our stomachs have developed a resistance to many antibiotics, and they can pass that resistance on to other bacteria.

Indeed, the resistance to antibiotics and other anti-bacteria medications is a deadly consequence of over use of antibiotics, and it is a key feature in the next deadly epidemic.

Bacteria are also long lived, some living for perhaps a thousand years in some singular environments. Many can also create "cysts" which are very, very durable.

Spread person to person? Yes
Novel features: Yes
Ability to kill: very high
Evolution rate: very high

One, of course, is a virus, the flu family. This family, even the same basic strain, can make you a little sick, or it can kill you. It has all the necessary skills to be our next big deadly epidemic, just as it has been an epidemic every 22 years for the last 300 or so. The current swine flu H1N1 will do just fine, and even has some anti-viral resistance going for it, since it is resistant to Tamiflu

This is very much the same flu that struck in 1918, eventually infecting one person in four in the US, up to half the population in some countries, and killing 600,000 in the U.S. Cities dug common graves to accommodate the dead.

It killed quickly. There are reports of people going out shopping and never returning home. People sometimes died within hours of the first symptom. Hospital emergency rooms stacked the dead out of the way to make room for new patients.

It killed the healthy. Most people who died were between 15 and 40. It is the body’s own reaction to the flu which brings death, an effect called the "cytokine storm" in which the body over-reacts to an invader, overcoming the respiratory system and causing death from suffocation in the body’s own fluids. This accounted for the "bluish tinge" of those about to die. A creaky old immune system could save your life if you get H1N1 Type A influenza.

The current swine flu is well related to the 1918 outbreak, and it is also killing the healthy.

The flu is a very likely epidemic or pandemic infection, and we might be seeing the first of it right now. The flu hits hard, moves fast, and often disappears as an epidemic in a few years. The flu could significantly impact many countries.

Already Mexico City has shut down all nightclubs, parties, schools, churches, indeed gatherings of any sort. The CDC is warning that this could easily become an epidemic or pandemic.

However, as likely is a flu epidemic is, it might not be the worst epidemic we experience. There is a second epidemic, already started, and it has cases in every nation including the US. Currently, the disease kills slowly. It is often kept in check with antibiotics. At least that’s the current state of this disease. It’s tuberculosis.

Tuberculosis has long been with humans, though it was only identified in 1882, and it was traditionally called the White Death or White Plague. It is caused primarily by Mycobactrium Tuberculosis.

It is currently the leading cause of death in developing countries, even though most of those who get the disease show no symptoms, and are not contagious. A third of the world’s population has it; there is a new case every second.

The disease enters through the lungs and eventually moves throughout the body where it goes dormant. It may never re-emerge, or it may re-emerge each time the host is stressed by hunger, ecological factors, or other diseases. Indeed, TB owes much of its current strength to HIV, with which it is often an opportunistic infection.

There are two very important things about TB which make it a good candidate for a decades long, empire crushing pandemic:

1. It has increasingly developed resistance to one or more drugs which used to be very effective.
2. It used to kill quickly.

For TB to kill quickly something would have to change about its current "strategy." The bacillus does very well by just making its hosts sick. However, it used to kill quickly, and if a clear advantage presents itself, it might again kill quickly. The ecological change that would encourage a virulent TB is overcrowding. A very sick person weeping Mycobactrium Tuberculosis from every orifice and coughing it into the air would benefit a virulent strain, provided other hosts can’t get away. If the victim can be isolated, it is more advantageous for the bacillus, which is very, very hardy against heat and disinfectants, to lay low and come out in times of stress. Then, the bacillus are spread a few at time, over days and weeks. Should crowding take place, due to natural disasters, prison and housing overcrowding, or refugees from wars or other infectious epidemics, TB might spring forth in a virulent form. Given its durability, ability to spread from person to person or from food to persons, and given a new resistance to specific antibiotics and perhaps antibiotics in general, TB could become a horrible new killer, one with staying power. There is no way to guess at the global impact of such a disease.

We already have people living among us who live as if in those days. Despite the belief that homeless people enjoy great social services, for many homeless people any injury can mean death, because they are unable to obtain proper medical care. They might receive emergency room care, but are often not eligible for follow up care.

The growing number of people in the margin of our society are the breeding ground for the next epidemic. The treatment they and their fellows endure in other nations, particularly developing nations, encourages antibiotic and antiviral resistance.

Statistically, it is just a matter of time before an epidemic of the sort we thought was a century behind us strikes again. Like those before us, we will be terrified to go to the store, to visit sick relatives, to breathe the night air. In epidemics of the past the survivors became numb to death, to stench, to horrid suffering, and the death around them robbed them of the faith that they might escape.

In a way, the better our medical science gets, the more likely a terrible epidemic becomes. It is the nature of evolution, the give and take between predator and prey. Whatever advantage in understanding we gain, we can never match the durability and flexibility conferred on bacteria and particularly viruses, to multiply often and quickly.

One step, though, would be comprehensive medical care for all residents.

For more info on swine flu, go here.