David A. Markowitz

Scientist and engineer. I develop, scale, and apply biotechnologies to benefit society.

[David A. Markowitz @DavidAMarkowitz]

We're at the threshold of understanding intelligence itself. The convergence of neuroscience and AI has created an unprecedented opportunity — but our research ecosystem isn't built to seize it. We need a new model that matches the scale of our ambition... 🧵

[Polly Fordyce @fordycelab]

Characterizing AI-designed proteins requires quantitative biochemistry at massive scale. Enter Amplicon/Protein Bead Display (APB-Display), a fully in vitro platform that quantifies Kd's for >100,000 variants in <3 days (preprint link below!) @Stanford_ChEMH @czbiohub (1/n)

[Prof. Michael Lin @MichaelLinLab]

Excited to announce a powerful new one-two punch for voltage imaging from our lab and collaborators! In two new preprints, we introduce ASAP6c for high-throughput population spike-recording, and ASAP7yfor deep, subthreshold 2P imaging.
🧵 1/14

[Tom Kalil @tkalil2050]

Congrats to the @deliverome team for launching this important project, @AsteraInstitute for backing it, and @IFP for highlighting! I hope more philanthropists and foundations will support this initiative to improve targeted delivery of novel therapies.

[Jacques Carolan @JacquesCarolan]

I had an absolute blast chatting with @juanbenet about the future of neurotech.

For neurotech to reach everyone who needs it, we need treatments that are both more effective and dramatically easier to deliver. That’s the ambition behind the programmes I’m leading at @ARIA_research.

Juan is a super thoughtful host, and this is the deepest conversation I've had about my journey, what it means to lead ambitious R&D, and the future we could unlock if next-generation brain therapies can genuinely scale.

[The Deliverome Project @deliverome]

Today we're launching Deliverome Bio, a focused research organization tackling one of the biggest bottlenecks in medicine: getting therapeutics to tissues beyond the liver.

[Juan Benet @juanbenet]

Episode 3 of my new podcast features Dr. Jacques Carolan (@JacquesCarolan), a founding Program Director at ARIA (@ARIA_research), the UK’s Advanced Research and Invention Agency. He directs two neurotech programs aimed at one of the most important opportunity spaces: developing tools and systems to interface, at scale, with the human brain.

One program is built on the idea that brain disorders are circuit problems, and funds tools to target those circuits with molecular precision across the whole brain. The other aims to deliver high-performance neurotech to the brain non-invasively or at most in a 30-minute outpatient procedure.

We dig into the engineering and biology behind both programs, potential scaling unlocks for the field, how ARIA programs drive breakthroughs, Jacques background, the role of media in shaping the future, and much more. I hope you enjoy the conversation!

Other links to this episode and references below.

Chapters
00:00:00 Introduction
00:01:22 Why 20 years of neurotech breakthroughs haven't reached patients
00:04:08 The two variables that determine whether any medical technology gets adopted
00:09:17 Brain disorders cost the UK £100B/year and we're barely treating them
00:16:15 Using stem cells and gene therapy to build better brain interfaces
00:21:40 Self-regulating gene therapy that helps the brain quiet its own seizures
00:24:03 The non-technical reasons transformative neurotech fail to reach patients
00:31:34 Watching a 30-second brain ablation stop severe tremors
00:38:11 The case for delivering brain implants and therapies without opening the skull
00:50:56 Why high technical uncertainty makes distributed teams better than vertical integration
01:02:55 Why the UK keeps producing world-class neuroscience but not world-class neurotech companies
01:11:04 What AI-driven hypothesis generation means for breakthroughs per pound
01:20:40 From quantum computing to improv comedy to running £119M government brain programs

[Sean Escola @SeanEscola]

What is holding #neurotech back from being one of the greatest breakthroughs of our time?

Infrastructure.

We know neurotech works & the promise is huge, but getting from approval to access takes years — delaying both patient access & company capital.

Our goal at PL Neuro is to break these bottlenecks.

Here we share a roadmap for navigating this at the field level — because if we want to fix it, it’s going to be all hands on deck: https://t.co/lMHfPhev7i

[David A. Markowitz @DavidAMarkowitz]

Governor of Texas @GregAbbott_TX just ordered a statewide medical cybersecurity review based on my team's work for @ARPA_H. Fantastic real-world impact for patients! 👇 https://t.co/amvCRW1l8t

[David A. Markowitz @DavidAMarkowitz]

🚨 There are 30M legacy medical devices in the US and 6.2 vulnerabilities per device. Our health infrastructure is NOT SECURE. To fix it, we need tools that automate vulnerability detection and remediation at scale. Today, my team is releasing those tools. 🧵

[David A. Markowitz @DavidAMarkowitz]

@dfirgs @RenPhil21 @AsteraInstitute @tkalil2050 @KumarAGarg @elidourado Super excited to see this materialize!! I first saw @tkalil2050 present his vision for unlocking DAFs as impact capital in 2019, back when it was "only" a $120B oppty space. The fact that it's now a $250B space shows there is an urgent market need for help deploying capital.

[David A. Markowitz @DavidAMarkowitz]

@BrackLab @LifeSciVC @DARPA @ARPA_H Concrete example: as an IARPA PM, I funded a buzzy VC-backed startup in a hot biotech IPO environment. The company underperformed on my program, so we cut them. If IARPA had an equity stake in the mix, I might have felt pressured to "play ball" until realizing a financial ROI.

[David A. Markowitz @DavidAMarkowitz]

@BrackLab @LifeSciVC @DARPA @ARPA_H Here's the failure mode: A typical ARPA R&D contract can be canceled for underperformance or just USG's convenience. If a performer awards equity to USG in exchange for maintenance of a contract through certain milestones, it creates a financial conflict of interest for USG.

[E11 Bio @E11BIO]

How to make frontier AI models safer and accelerate drug discovery with the connectome. We are featured in this @IFP article by @AdamMarblestone & @Andrew_C_Payne

[David A. Markowitz @DavidAMarkowitz]

But - and I can not stress this enough - to build a BBN:

You. Need. To. Know. How. To. Sell.

[David A. Markowitz @DavidAMarkowitz]

This piece deserves more attention.

[Eric Gilliam @eric_is_weird]

The addition of @Convergent_FROs to the R&D ecosystem has been a game-changer. But fundraising for new FROs is a bottleneck

Today’s FreakTakes outlines a model to help ambitious field strategists with vision build FRO-like orgs with less upfront capital
https://t.co/PwIpWEiw65

[David A. Markowitz @DavidAMarkowitz]

If your mission is to be the world's R&D leader in your technical area, and you are willing to work part of the time on other people's important problems, the sky's the limit on external funding availability - much of which can then be used to fund your passion projects.

[David A. Markowitz @DavidAMarkowitz]

A very well capitalized US biotech CEO told me yesterday: "Our investors are telling us to do everything in China now. Something that used to take 4 years and cost $100M in the US can now be done in 2 years for $20M by Chinese partners."

[David A. Markowitz @DavidAMarkowitz]

...which is another way of highlighting that the monetizability of neural interfaces is unlikely to scale with their throughput over the next 10+ years*

*assuming a revenue model that is based on insurance reimbursements

[David A. Markowitz @DavidAMarkowitz]

What's the strongest current thesis for a problem that can only be solved by bidirectionally interfacing with *millions* of neurons in the human brain?

[David A. Markowitz @DavidAMarkowitz]

My two cents: if you gave this capability to a neuroscientist, it would revolutionize how we study the non-human brain in a basic research setting. Clinically, I think this capability would far outpace our current best ideas about how to intervene in any human brain disorder.