Jacob Kimmel

They're mostly nucleus.

They grow really, really fast.

They look different.

They detach from a dish.

They grow up into a 3D structure.

And they express some genes that will just never be turned on in a fibroblast by definition.

So actually how he ran the experiment was he just set up a simple reporter system.

So he took a gene that should never be on in a fibroblast, should only be on in the embryo, and he put a little reporter behind it so that these cells would actually turn blue when you dumped a chemical on them.

And then he ran this experiment in many, many dishes with millions upon millions of cells.

The second really key feature of the problem is this notion that those cells he's converting into amplify.

They divide and grow really quickly.

So in order for you to find a successful combination, you don't actually need it to be efficient almost at all.

The original efficiency Yamanaka published, the number of cells in the dish that convert from somatic to an induced pluripotent state back into a stem cell is something like a basis point or a tenth of a basis point, so like 0.01, 0.001%.

If these cells were not growing and they were not proliferating like mad, you probably would never be able to detect that you had actually found anything successful.

It's only because success is easy to measure once you have it, and even being successful in very rare cases, one in a million,

amplifies, and you can detect it, that this I think was amenable to his particular approach.

So in practice, what he would do is dump these factors or this group of 24 minus some number, eventually whittling it down to four.

He would dump these onto a group of cells.

And over the course of about 30 days, just a few cells in that dish, like a countable number on your fingers, would actually reprogram.

But they would proliferate like mad.