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Genetically-engineered organisms
We can, and have, genetically-engineered self-replicating organisms, albeit only in the limited sense of modifying that which exists, not in simply creating things from scratch.
It seems likely that our ability to create and manipulate life will only increase in the future. There are countless potential benefits, and so we have tremendous incentive to explore and expand our knowledge of and use of such technology.
But it also seems certain that we could construct an organism---be intentionally or unintentionally---that is capable of wiping out humanity.
It's hard for me to guess how high the the risk here is. There have been many deadly forms of life that Mother Nature has produced. Many of those have annihilated other species. A very few have created extinction events, rapid, mass die-offs of many of the species on Earth. We ourselves perhaps represent one of such notable killers in the history of life, though presently are greatly outmatched by things like blue-green algae.
But...whether it is some kind of pathogen, an unintentional mutation in something that we create, or similar, it seems likely that we could create something that would end humanity. Mother Nature has tried many forms of life over the eons. Her most potent tools are natural selection, with the later development of sexual reproduction greatly increasing the rate at which change could propagate.
When we developed artificial selection, we got the ability to much-more-rapidly reshape life. Genetic engineering has allowed us to jump forward again, much more rapidly.
I do not know how widely-available genetic engineering capabilities will spread among humanity. It may be that, with the advance of technology and software, it will become as viable for any given human to create dramatically new forms of life in the future as it is to print a document on paper today. That seems likely to create an unstable situation.
I think that often, the risks of biological warfare are overstated. The military use of biological weapons has been limited; they are difficult to control, and generally pose risks to their wielders.
In general, where biowarfare has been pursued, things like anthrax have been of more interest, where the biological weapon acts more like a chemical weapon, and does not really lend itself to rapid, uncontrolled replication. This is, no doubt, a dangerous weapon, but governments have generally not shown a tremendous military interest in engineering pandemics.
Disease certainly has been used in warfare. Most-recently, Japan made some use of disease in World War II in China, and considered, near the end of the war, doing so against the US in Operation Cherry Blossoms at Night. This would not have posed an existential threat, but it does show that the will can exist, and one might imagine genetic engineering creating biological weapons that do spread.
But, in general, I think that it is less-likely that countries would intentionally produce organisms with existential threat potential to humanity as military technology, and more-likely that an existential risk would come from some sort of non-state actor who can leverage spreading access to genetic engineering, or to some kind of engineered organism intended for some civilian application that spins out of control.
In 2026, we probably have the ability to create terrible pandemics. We could, probably, say take pathogens like smallpox and engineer variants to defeat vaccines. I have not looked deeply into the kind of harm that someone could manage with existing technology. I think that given that our ancestors fought for survival against billions of years of all kinds of life forms, it probably wouldn't be the easiest thing in the world to kill humanity, given present-day technology, and that gives me some reassurance about our ability to deal with an accidental, self-replicating pathogen. But if one considers how devastating multiple concurrent threats can be to life, I am not certain that someone with the will and current technology could not create incredibly dangerous concurrent pandemics. Consider how we make use of combination antibiotics as a weapon against against pathogens, because it is much harder for a strain of pathogens to simultaneously develop immunity to multiple antibiotics; one that develops immunity to one may be killed by another antibiotic before it can spread. Or, in the case of humanity, what happened to New World humans when the Columbian exchange occurred, where many diseases struck a large human population at once:
https://en.wikipedia.org/wiki/Columbian_exchange
The Columbian exchange, also known as the Columbian interchange, was the widespread transfer of plants, animals, and diseases between the New World (the Americas) in the Western Hemisphere, and the Old World (Afro-Eurasia) in the Eastern Hemisphere, from the late 15th century on. It is named after the Italian explorer Christopher Columbus and is related to the European colonization and global trade following his 1492 voyage. Some of the exchanges were deliberate while others were unintended. Communicable diseases of Old World origin resulted in an 80 to 95 percent reduction in the Indigenous population of the Americas from the 15th century onwards, and their near extinction in the Caribbean.
Even if it would be hard for someone to create a single humanity-killing disease using 2026 technology, perhaps they could create a cornucopia and release them concurrently to increase their efficacy. And in the future...well, it's hard to know what we might develop the ability to create.
Genetic engineering has enormous potential benefits. Disease resistance. Greater productivity of plants and animals. The ability to create "biological factories" for any number of new, valuable things that as of yet, we do not have. We will probably not readily swear off genetic engineering, since it has such tremendous benefits. But those incentives also means that we will probably always be exposed to potential risks.
Self-replicating nanotechnology
We are not yet to the point where we can build small, self-replicating robots. But it seems likely that, sooner or later, we will be. There are such potential benefits in materials science and manufacturing that it seems hard to believe that we will collectively choose not to build such a thing.
Once we have done so, we create the potential for a gray goo scenario.
https://en.wikipedia.org/wiki/Gray_goo
Gray goo (also spelled as grey goo) is a hypothetical global catastrophic scenario involving molecular nanotechnology in which out-of-control self-replicating machines consume all biomass (and perhaps also everything else) on Earth while building many more of themselves,[1][2] a scenario that has been called ecophagy.[3] The original idea assumed machines were designed to have this capability, while popularizations have assumed that machines might somehow gain this capability by accident.
Self-replicating machines of the macroscopic variety were originally described by mathematician John von Neumann, and are sometimes referred to as von Neumann machines or clanking replicators.
This bears a lot of similarities to the potential harms from genetically-engineered organisms; life as nature has created it is simply one type of self-replicating machine. We can, via modifying existing life, produce more-sophisticated and self-replicating things through genetic engineering than we can via crafting self-replicating machines from scratch. But...I think that it seems likely that over time, we will catch up when it comes to self-replicating machines, to no longer stand on Mother Nature's shoulders and billions of years of evolution. I think that most of the incentives and risks and such for self-replicating nanotechnology are similar to those of genetic engineering.
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