Events that occurred in other fields of biology, distant from ours, that came together under, again, accidental circumstances. Very fortuitous circumstances, that resulted in an explosion of information and the resolution of the question, what is the molecular nature of the counting mechanism. A very interesting story.
The first event has to do with a discovery that was made in the early 70s, I believe, by a Russian theoretician, actually, by the name of Alexey Olovnikov. It was also, this belief... or this theory, also had important input from a paper published by James Watson. I'm... I'm certain the two researchers didn't know what the other one was doing, but they more or less thought about this possibility at the same time, although Alexey's thinking was far more on target. Alexey had left a lecture in Moscow, in which my work was discussed by one of the – actually – leading biologists in Russia at that time, and Alexey heard for the first time about my work, and he wondered about this question of why there was a finite lifetime to cultured normal cells. As he was wondering, he descended to a Moscow subway station and had a brilliant insight as he stood on the platform waiting for the subway train to arrive. At that time – to back up and give you some notion of what insight he had – you need to know that a puzzle existed in the field of DNA replication. DNA, of course, is the fundamental self-replicating molecule that contains all of the genetic information that yields, essentially, in the long run, an animal or a plant, or any living material. So it is the fundamental molecule of life. The question then arose that because it was understood, to some extent, how DNA replicates itself, which is one of its major capabilities... it was understood that the DNA replicates itself using an enzyme called a polymerase.
This enzyme runs along the length of the DNA molecule, which is quite long, and adds to it the nucleotides, or the chemicals, that compose this DNA strand. As it runs along the mother strand, if you will, it picks up the chemicals from the environment and attaches them to each other, and as it rides along the mother strand it reproduces the mother strand, more or less as the mother strand existed, although that's not quite accurate, but for purposes of a simple explanation, it's not necessary to know any more detail. The problem was that it became apparent that the polymerase that was copying the mother DNA strand did not copy the strand to the end. There are known reasons for this, it happens to do... it depends on the chemistry of the polymerase, so we knew why it didn't copy to the end, but we couldn't understand how that would continue to exist, because if the DNA strand is not copied in its entirety at each round of division, then ultimately you're going to be losing the end of the DNA strand and genes will be lost, because the DNA, obviously, is where all of your genes are located, and that would become very apparent quickly in any animal or plant, because it would lose major properties and the species would die... probably the species would never exist, under those circumstances. So this was a major puzzle. It was called 'the end replication problem'.
