Cell

Now, that sounds almost like a news article or a, a news article about a scientific paper, but that's actually the title of the scientific paper, which was published in the journal Science, which is one of the three apex journals.

You know, scientific publishing is competitive, but it's especially competitive to get manuscripts accepted into Science, into Nature, and into the journal Cell.

So it represents kind of the, one of the kind of Super Bowl, uh, NBA championships, and Stanley Cup, if you will, for you sports aficionados of scientific publishing.

This is a paper from Matthew Killingsworth and Dan Gilbert.

And nitric oxide is enormously important for, um, for your heart, for cardiovascular and metabolic function.

And many, uh, health disorders have been associated with, uh, compromised nitric oxide synthase.

That's the enzyme that makes nitric oxide, uh, uh, to, to do that.

Now, let me talk a little bit about nitric oxide synthase.

Okay? And then that has-- that goes to the heart and has various targets.

Completely, completely different, uh, mechanism.

This would mean that the cardiovascular benefits of dietary nitrate, like leafy vegetables and beets and so on, which, you know, you should eat if you want good heart health, they're probably mediated by microbially generated DNICs rather than by the nitrate, nitrite, ni- nitric oxide pathway that we think is currently the reason why these vegetables are good for you.

So that's a huge paradigm shift.

I wanted to screen through those compounds very quickly, and I didn't wanna, like, have to stay up all night long, night after night, doing it one test tube at a time.

Uh, and a lab across the hallway had this, uh Cell washer, right? It would just, it would suck up 12 rows on a 96-well plate all at once and filter the contents on glass fiber filters.

Um, and the, the, the assay that, that was, you know, well accepted and was being run to, to assay protein kinase C back in those days was a glass fiber filter.

So it was a really natural kind of extension to just say, "Oh, I can just miniaturize it and do it 12 at a time." [inhales] Um, so developed that assay and then, you know, d- got really beautiful, um, sort of inhibition curves on all 50 of these compounds, and then put together a very sort of simple structure activity relationship map, uh, and found one, actually two very potent inhibitors, and one turned out to be quite selective, at least when we screened it against a few other serine/threonine kinases.

Uh, I really developed a strong love of cancer biology and trying to understand it.

But at the end of the day, I think I was a postdoc there for five years, and I realized I have to get out, right? I have to become independent and find a job.

So basically looked at every job that was listed in, uh, "Science, Nature, and Cell," whether it was in academia, industry, or, you know, there was also the NIH jobs and, and other sort of research institute jobs.

And I think I sent out somewhere on the order of 50 letters in the course of a two or three-week period.

So we did not contact, uh, Emmanuel at that time, and instead we just, uh, uh, trying to finish the paper as soon as possible.

And true story is that at that time, suddenly, this, uh, famous editor, Ben Lewin, [chuckles] from Cell, he suddenly called me out of the blue.

So because we published this discovery of orexin as a new neuropeptide about one year earlier in journal Cell, so he knew me.

And so he called me suddenly that, "Well, Masashi, could you review this new paper, new manuscript submitted by somebody in Stanford?" No, this is true story

Oh my-

the story because I, I was, I was not sure, is that true or not true? But to be honest, when you have something like this, you use it to whip up your troops to work even harder.

Uh, and we worked very hard, and then we finished the story.

We found the mutation, and then we submitted to Cell, and that's when he got the paper.

Together, they mapped a complete intact male fruit fly brain.

They just published these findings in the journal Cell.

The absolute scale of the numbers involved here is staggering.

We are talking about a creature smaller than a grain of rice.