Despite his brilliancy and longevity, we are asked to believe that, although he had managed to keep the stone safe from who knows how many dark lords for approximately 600 years, he was unable to protect it from Voldemort and prevent its destruction in 1992.
I'm not sure I believe it, so I've been exploring other possibilities for what may have happened. Here's what I've considered:
1. Dumbledore took the stone without Flamel's permission
Given what we learned of Dumbledore in DH's, this doesn't seem totally unreasonable. However, I really doubt that Dumbledore would have been able to access the stone without Flamel's consent. Moreover, even if he was, he wouldn't have been able to get away with it for very long since its removal from Gringotts was announced in the Daily Prophet.
2. The stone at Hogwarts was actually a fake, so they didn't really die when it was destroyed.
This feels like the easiest explanation, especially since Hagrid was the one assigned to retrieve it from Gringott's, but I don't think it quite works. The brilliant swythyv proposed a few years ago that Nicholas Flamel had ruled as the "invisible king" of the wizarding world for nearly seven centuries. He left the Wizengamot in charge of managing most of its affairs. Dumbledore had so much political power in the WW mostly because he had Flamel's backing. Therefore, Flamel's death would explain why Dumbledore's political star fell so quickly after Harry's first year. So, if we go with her theory, it would seem that Flamel was definitely out of the picture by 1992.
3. The Flamels had already simply decided that they were ready to die, so they didn't mind if the stone was destroyed.
Maybe. But, if they were, in fact, the sovereigns of the WW, this seems like really bad timing on their part, since Voldemort was still on the loose.
4. The stone at Hogwarts may or may not have been a fake, but, either way, the real stone was still destroyed because that was the only way to keep it out of Voldemort's hands.
In part 7 of his 2004 Expecto Patronus series, pharnabazus presented a good theory about this.
Voldemort's principal aim, once the civil war had begun, would have been to clear his way to the Stone. Whatever charms protected the Flamels he would have circumvented or broken; whoever knew about these protections would have been taken, one by one, and made to reveal all that they knew.It's a really good theory, but, again, I'm not sure it quite works. Waffling wasn't around until the 20th century. There surely must have been other super-evil, super-smart dark lords in the previous centuries from whom the Flamels were able to protect the stone. Was Voldemort really that special? Moreover, we now know that Voldemort already had alternative arrangements for immortality in place, so it's hard to tell if he was, in fact, that desperate for the stone until after he lost his body.
The key figure may perhaps have been Adalbert Waffling, the magical theoretician, whose theoretical breakthroughs apparently affected the lives of "every modern witch and wizard." Waffling died before his time at the age of eighty in the suspicious year of 1981. (From what the chocolate frog cards say, the average age of natural death for wizards of his generation seems to be about a hundred). In other words, he was almost certainly a wartime casualty, and must have been killed shortly before the Potters were. The Flamels (in the Philosopher's Stone) had their own personal goldmine, and could have afforded the best theoretical magic to protect themselves and their stone. Waffling's death may have opened the way for Voldemort to reach the Flamels (or possibly to break into the Gringotts vaults) but before he could capitalise on it, he made a fatal mistake at Godric's Hollow. Voldemort no doubt calculated (as soon as he had heard of the prophecy) that removing a wizard who could defeat him was an even more urgent priority than getting the Philosopher's Stone
The Flamels were safe for now, and as long as Voldemort was in exile the Philosopher's Stone could be safe in Gringotts, but now they could see that if he ever returned its protection would depend entirely on their old friend Dumbledore....
5. The Flamels were actually already dead before the beginning of PS
And this is where I've landed. How can we be sure that Flamel was still alive in 1992? The kids found it nearly impossible to find any information on him. We don't know if there had even been any news about him since he published his work with Dumbledore on the uses of dragon's blood, and that could have been more than 50 years earlier. If Flamel was ruling the WW, he was doing it very much behind the scenes. He may have only been in contact with a few individuals, such as Dumbledore. Only they would have known if Flamel had died. And, just maybe, they wanted to keep his death a secret for as long as possible in order to preserve the political status quo (in other words, retain their power).
So when might the Flamels have died? There are probably a few good possibilities, but I think it could have been as early as the early 20th century. It might explain why both Grindelwald and Voldemort were allowed to run amok for so long... and why Dumbledore was able to get away with so many of his hair-brained schemes.
So what changed in 1992 that we finally learned of Flamel's death and Dumbledore's political clout seemed to suddenly take a nosedive? Maybe somebody else important had recently died. Along with Dumbledore, they had been keeping Flamel's death a secret, and now they were gone.
We have a few candidates for whom the individual(s) might be:
Pollux Black died in 1990
Perpetua Fancourt, noted on her wizarding card for inventing the Lunascope, died in 1991
Tilly Toke, who gained Order of Merlin, First Class for saving muggles from a dragon in 1932, died in 1991
Acturus Black died in 1991
Cassiopeia Black died in 1992
My money is on one or more of the Blacks. Others have noted that the Blacks appear to have been Wizarding Britain's royal family. They are the "The Noble and Most Ancient House of Black," and their tapestry goes back seven centuries (similar to Flamel's supposed 667 years of life). Note, also, that the Black family vault in Gringotts, vault 711, was quite close to the vault containing the stone, vault 713.