Dr. Leonard Zon on the Secrets of the Zebrafish

Len, let's talk about stem cells and cancer.

I think probably people in the stem cell community know that stem cells can be good and bad.

I certainly had no idea.

I thought stem cells were just all good.

But when I had a conversation with you, you said, listen, we discovered that.

cancer begins with a stem cell state and so let's talk about that you found that with melanoma yeah because we've known about how stem cells can help beat cancer actually they can be the the the origin of cancer so you found that cancer begins from one cell a single cell that reverts back to a stem cell state and then it becomes cancerous and the the cancer grows you found this in melanoma tell me about how the zebrafish helped you discover this and what is next

Yeah, it's a really good story.

So what happened was Chuck Kaufman in the lab was studying the origin of melanoma.

And we always thought that cancer should start as a single cell, but nobody had ever actually seen this happen in the body.

So what had happened is that we have been studying melanocytes, which are the pigment cells of your skin.

Now, melanocytes come from a stem cell population called the neural crest.

So during embryogenesis, the stem cell population eventually differentiates to make the melanocytes.

And what we saw, he made a reporter for the neural crest stem cells.

When he looked at tumors and saw that the very beginning of the tumor, he could see that this reporter came on.

And it came on really early.

So he decided to follow an entire cohort of fish pretty much every day for a couple months until they developed tumors.

And what he could see is an adult fish, and they had one cell that was green.

And 100% of the time, that one cell was the beginning of the tumor, and you could see it develop over time.

So we had been the first people to ever see cancer at the one cells stage.

And, you know, we think about embryogenesis, you start as one cell and you develop well, the same thing is true in cancer.

You start as one cell and you develop.

So the surprise was the initiating event of starting a cancer.

was to take a melanocyte and go backwards in development.

So it actually reprograms itself to become a stem cell.

And at that particular point, it becomes tumorigenic and starts to grow out of control.