Even with all the scientific and technological advances of the last two millennia and especially of the last century, humankind itself has not really changed. The stories we read in our most ancient books do not seem alien to us. On the contrary, the humans who wrote those works had the same needs and desires that we have today, though the means of meeting those needs and of fulfilling those desires may have changed in some of the details.
The human species has managed to survive a great number of truly monumental catastrophes, some naturally caused (floods, droughts, tsunamis, glaciations, etc,) and some the result of its own doing, often with the help of science and technology (especially in creating the tools of war). But such calamities did not really "change everything." (This statement is certainly not meant to minimize the tragedy of the millions of lives lost in these catastrophes.) Though we worry about the possible dramatic effects that an anthropogenically changed global climate might have, humankind itself will survive such changes (because of its science and technology), though we cannot predict how many people might tragically die because of it.
In terms of "what will change everything" the larger view is what will significantly change humankind itself. From this human perspective, the last "event" that truly changed everything was over some period of time around 50,000 years ago when evolutionary advances finally led to intelligent humans who left Africa and spread out over the rest of the world, literally changing everything in the entire world.
Prior to that evolutionary advance in Africa, our ancestors' main motivations in life were like any other animal — find food and avoid death until they could reproduce. After they evolved into intelligent beings their motivations in life expanded. Although they still pursued food and sex and tried to avoid death, they also spent increasing amounts of time on activities aimed at preventing boredom and making them feel good about themselves. These motivations have not changed in the succeeding millennia, though the means of satisfying themhave changed often.
How humankind came to be what it is today was a result of natural selection. Humans survived in the hostile environment around them (and went on to Earthly dominance) because of the evolved improvements in their brains. One improvement was the development of curiosity and a desire to learn about the environment in which they lived. But it was not simply a matter of becoming smarter. The human species survived and succeeded in this world as much because of an evolved need for affection or connection with other human beings, a social bond. It was both its increased intelligence and its increased social cooperation that led to increasing knowledge and eventually science and technology. Not all individuals, of course, had the same degree of these characteristics, as shown by the wars and horrendous atrocities that humankind was capable of, but social evolution driven by qualities acquired from the previous species evolution did make progress overall. The greatest progress and the greatest gain in knowledge only happened when people worked with each other in harmony and did not kill each other.
The evolution of human intelligence and cooperative social bonding tendencies took a very long time, though it seems quite fast when appreciating the incredible complexity of this intelligence and social bonding. How many genes must have mutated and been naturally selected for to achieve this complexity? We are here today as both a species and a society because of those gene changes and the natural selection process that over this long time period weeded out the bad changes and allowed the good changes to remain.
Technically, evolution of the human species as a result of natural selection stopped when we became a social animal — when the strong began protecting the weak and when our scientific and technological advances allowed us to extend the lives of those individuals unfortunate enough to have genetic weaknesses that would have killed them. With humans, artificial selection (selective breeding) was never a serious replacement for natural selection possibility, and as a result there have been no significant changes to the human species since its societies began.
But now, with the recent great advances in genetic engineering, we are in a position to change the human species for the first time in 50,000 years. We will be able to put new genes in any human egg or sperm we wish. The children born with these new genes will grow up and pass them on to their children. The extensive use of this genetic selection (or should we call it anthropogenic selection) will rapidly pass new genes and their corresponding (apparently desired) traits throughout the population. But what will be the overall consequence? When selecting particular genes that we want while perhaps not understanding how particular gene combinations work, might we unknowingly begin a process that could change our good human qualities? While striving for higher intelligence could we somehow genetically diminish our capacity for compassion, or our inherent need for social bonding? How might the human species be changed in the long run? The qualities that got us here — the curiosity, the intelligence, the compassion and cooperation resulting from our need for social bonding– involve an incredibly complex combination of genes. Could these have been produced through genetic planning?
Our ever-expanding genetic capabilities will certainly "change everything" with respect to medicine and health, which will be a great benefit. Our life span will also be greatly extended, a game-changing benefit to be sure, but it will also add to our overpopulation, the ultimate source of so many problems on our planet. But the ultimate effect may be on the human species itself. How many generations might it take before the entire human race is significantly altered genetically? From a truly human perspective, that would really "change everything."