Dr. David

Liu.

The December of my freshman year, E.J. Corey won the Nobel Prize in Chemistry for his contributions to synthetic organic chemistry, which is a field that teaches how to construct complicated small molecules from simpler materials and is sort of the backbone of the traditional small molecule pharmaceutical chemistry industry.

my training as a chemist would sort of morph in part in E.J.' 's lab into an interest in molecular biology and into DNA.

And so when I then did my PhD in Peter Schultz's lab at UC Berkeley at the time, I was very interested in evolving molecules and in manipulating DNA to support the evolution of proteins and I was hoping to plant the seed for the evolution of synthetic molecules as well.

So then when I became an assistant professor, right after getting my PhD in 1999, I launched our group on a series of projects, a major one of which was how to perform chemistry on DNA molecules that were attached to the precursors for drug-like molecules.

In other words, how to do DNA-encoded small molecule drug library synthesis as a way of expediting small molecule discovery for biologically active compounds and for applying some of the powerful principles that drive biological evolution to the discovery of small molecule therapeutics.

with TFR1 capsids.

Tell us about this recent incident.

Okay.

So, what happened was that last Saturday, I went to support a dear friend of mine, also an ally of mine, Steve Hilton.

He had a rally, a council meeting in San Gabriel.

San Gabriel is also part of my district.

I went and I was inside town hall for a little bit.

Then I came out.

Tell everybody where they can find out more about your campaign for state assembly.

Why don't you tell us about a few of them?

Yeah, so the first one that we interviewed was actually foreign and domestic.

So Sarah Hurd and Nathan Lemley, I got to see their story kind of unfold right in front of me.

I had met the owners shortly before lockdown.

And as soon as lockdown happened, I was one of their first to-go orders.

And they had never really done to-go in that manner.

And seeing the types of pivots that they had to go through to make it, I mean, that's kind of the start of our friendship and the start of me thinking about it.

How did your experience with Austin restaurant or Austin dining change over the course of making this film?

Tell us about this recent incident.

Okay.

So what happened was that last Saturday, I went to support a dear friend of mine, also an ally of mine, Steve Hilton.

He had a rally, a town hall meeting in San Gabriel.

San Gabriel is also part of my district.

I went and I was inside town hall for a little bit.

Then I came out.

Tell everybody where they can find out more about your campaign for state assembly.

What are some of the challenges of making these therapies more financially viable?

So there are some genetic disorders, sickle cell anemia, now called sickle cell disease, being the poster child, that have a prevalence high enough that clearly an effective treatment can be profitable enough to recoup the costs and more, which is why so many genetic medicine companies have pursued sickle cell disease.

So gene editing medicines and genetic therapies in general, especially if it's a one-time gene editing treatment that can cure the patient in principle for the rest of their life, can be financially viable for diseases where there are at least thousands of patients that you can treat The typical genetic disease patient, although that itself is sort of an oxymoron, but the average genetic disease patient costs the U.S. healthcare system between $2 and $10 million over their lifetime.

So there is some room for these treatments to both help patients and their families and end up saving the U.S. healthcare system money in the end.

But it does get a lot harder once the number of patients in a disease falls below thousands.

In some cases, science can help.

The simplest way to imagine gene editing is the baby KJ story where there's a mutation that causes a fatal genetic disease and you correct the mutation back to the normal sequence so the disease is no longer present.

And so I

The question is what the regulators say, right?

Well, at least for highly regulated institutions at time of onboarding, I'm pretty confident the answer will be no. Yeah, I agree.

Anyway, so because of all of this, I think behavioral biometrics will continue to be really useful.

Then after that, there's all the information you put on the application, the phone, the email, etc.

And in my hypothetical example, I said, well, we're compromising the phone.

And the way we're doing that is by getting a different phone number that was associated with you and an email, but the email is not associated with you.

And I think coverage of email ownership in the US maybe is 50, 60%.

There was a very massive change.

Okay.

And, you know, we got all the stuff from, like, the Sender films, like, you know, uh, festivals, and you got to see, and I got to go to Yosemite and actually climb in Yosemite, and, like, that, to me, was such a, a gift to g- to see that part of history.

Like, Valley Uprising was interesting because as somebody who didn't come from that world, it gave me what I felt like the history and the context to do it, and that was kind of, like, the gateway.

And then the rest of the world, the documentaries started showing up.

Um, I think another, another one that was prior to that, which was more of a series, was Chef's Table, right?

I love it.

Because then you can, you can go somewhere.

And I think we need to be okay with doing that with more of these films, because if I had stopped at any point to listen to other people's advice and stop the film, or have done something to cheapen out the effect of the storytelling, then I don't think we'd a- we'd have a film that's as, as impactful as this.

Is that correct? Tell me about that happening.

Yeah, I was on the board of a company and one of our fellow board members happened to live in this area in the Pacific Northwest.

It's called the Willapa Bay.

It's been written up as the cleanest bay in North America.

And it's just beautiful and pristine.

It's a massive body of water.

And one of the sort of unique attributes of it is that close to 80% of the water moves out on every tidal turn.

Restaurants

Can you talk about that?

Sure.

So the baby is KJ Muldoon, and this is work that was co-led by Kiran Musunuru and Rebecca Arons-Nicholas, both at Children's Hospital of Philadelphia and, and UPenn, and involved many, many researchers.

So it's very important to give credit where credit is due.

It's, this is a, the definition of a village effort.

Our lab developed the base editing technology that was used to correct KJ's mutation, but many labs contributed to identifying which flavor of base editor was the best to use, manufacturing it, making the cells and the animal model, the mouse model, and doing the monkey studies that were needed to de-risk to the extent possible the treatment.

This is a very special case because the disease that KJ suffered from was a single letter change in a gene called CPS1 that has, as a consequence, that ammonia levels are elevated and can't get cleared through the normal mechanism, and that can be very toxic.

Can you please explain in simple layman's terms what these are?