Okay, I want to kick off by asking, what made you guys interested in writing about Matt Wilsey's experience and his company, Grace Science?

Well, we'd both been hearing about Matt's work.

We'd been following it for a long time.

Jorge Conde, who's a friend of Matt's and a well-known venture capitalist, actually reached out to me and said, look, you guys have to write this story.

There's a fantastic story to be done here that gets at a lot of the tensions and rare... disease drug development.

And I talked about it with Jason, and then he was just insistent that we had to find a way to get this one done.

We were not lucky given the size of the market.

Matt, there are researchers who feel that what you've done has been heroic, but there are people who feel both that the efficacy that you've been able to show so far or the evidence of it is limited and that the manufacturing data that the FDA is looking for for this therapy is really necessary.

Matthew, how big a deal is this?

Well, depends what part you're asking.

I think the idea of this, uh, gene therapy is potentially revolutionary and is a big deal.

Um, I've thought that since Sakari Kartha Thiersten, who founded this company, this is a cardiovascular geneticist, I know him pretty well, um, had the idea, and it's a radical solution to the problem that we know that bad cholesterol, low-density lipoprotein, uh, causes heart attacks.

We know that drugs that target PCSK9, which is the target of this gene editing, uh, reduce that risk.

Um, we know that statins, which also hit LDL, reduce that risk.

We know that people don't take them, so Sakes' argument was, well, there are probably people who'd be willing to edit their genomes, and then they have lifetime low risk, and the scientific argument there makes sense.

How can these two things coexist?

Matt, can you give us a quick summary of what happened this week?

So one of the big ideas for mRNA vaccines has always been to develop flu shots using that technology.

You can pick flu strains faster.

It should be a good thing.

Moderna ran a global randomized clinical trial with 41,000 volunteers that compared their experimental mRNA flu shot to a standard dose flu vaccine in people aged 50 and older.

Moderna's vaccine was 27% more effective at preventing influenza-like illness and 49% more effective against hospitalizations.

But the FDA, or in this case, specifically Vinay Prasad, told Moderna that its clinical trial was not adequate and well-controlled, and therefore its application would not be reviewed.

Stephen, welcome to The Read Out Loud.

So Matt, fill in the picture about the scope of what's happening here, the range of, of staffers who are being cut.

Oh, it's very, very broad.

Um, I mean in the CDC we're talking tobacco control, injury prevention, workplace safety, birth defects, reproductive health, basically everything that is not infectious disease.

And at the FDA, um, the cuts are, I think, a lot deeper than a lot of people expected.

People who review new medical products, the people who actually look at a new drug or device, mostly seem to have been saved but, um, a lot of expertise late last week before the layoffs, the top vaccine official, uh, also in charge of gene therapy and, and the blood supply was removed, uh, today a director at the Office of New Drugs and the head of the Tobacco Center were removed.

Um, the former FD, several former FDA commissioners expressed concern including Scott Gottlieb, who was FDA commissioner under the Trump administration, worrying about a return to delays in drug approvals, and Robert Califf saying that, uh, the FDA as we know it is finished with most of the leaders with institutional knowledge and deep understanding of product development and safety no longer employed.

To what extent do these cuts reflect RFK Jr.'s desire to change the government's approach to public health?

Well, I think they certainly reflect that.