The Black Death in Europe and smallpox and measles in the New World were two instances where the human species went a noticeable part of the way towards extinction. Thus, I predict the end of humanity will be a series of bioengineered plagues.
Technology, management of public health, and even evolution and natural selection can effectively combat one pandemic, but will probably be overwhelmed if a large number of different new contagious deadly diseases were suddenly simultaneously unleashed upon the world.
Advanced technology coupled with our own curiosity and stupidity will cause this scenario. We first need a day when most people own a table-top virus generator. We'll say virus generically to mean some microorganism: bacterium, prion, protist, fungus, or perhaps some form of yet undiscovered or even fully synthetic form of life.
Everyone will own one of these appliances because, like a microwave today, it will be splendidly useful. You go on the Internet and download an appropriate DNA sequence, input it into the appliance, and it will synthesize a microorganism which creates a drug, condiment, cleaning product, skin lotion, printer ink, air freshener, or many other sorts of useful household items. It's a Star Trek replicator for chemicals.
One day someone will probably post the sequence to a single terrible disease (actually, plenty of dread diseases have already been sequenced and published), but this will not be a problem. The CDC can download the sequence, too, and even if there is an epidemic, it will fail to cause complete human extinction for the reasons mentioned above.
The real danger is instead of giving a man a fish, you teach him to fish, that is, let everyone be able to design a different new terrible disease. Beyond the table-top virus generator, we would need three more major advances in technology.
The first is a virtual pathogenic model of the human body. The second is a computer program that will use this model to randomly design particularly virulent diseases. The third is a computer in every home capable of running that search program. Intense research and development happens today in the first and third fields, while the second becomes easier and easier the more we understand disease.
All these technologies are decades if not centuries away. There will probably be safeguards against using one's virus generator this way, but safeguards may be subverted. Improvements in health care might outpace the apocalyptic combination, but then our civilization would live in the precarious state that only constant application of our technology wards off extinction.
Having armed everyone on the planet each with the ability to create a unique epidemic capable of killing, say, 50% of the population, how many curious people will try pushing the button? Today, on our planet of 6 billion, we would only need 33 crazy people to simultaneously release 33 independent pandemics in order to have a good chance of extinguishing the species. The expected number of survivors is less than one, 6e9 * 0.5^33. Are there less than 33 crazy people on the planet?
As described, the way this pandemic of pandemics spreads is mainly as information: information in the form of computer programs, pathogenic models, and virus generator technology. This means that even if humanity colonizes the stars, it will probably maintain an information link with the homeworld and other colonies, so the implements of our extinction can even cross the vast empty gulfs of outer space.
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