All-In Summit: Gene therapy and a new era of medicine with Dr. Nicole Paulk

This talk was recorded live at the All-In Summit 2023 at Royce Hall on UCLA's campus in Los Angeles.
(0:00) Besties welcome Dr. Nicole Paulk to All-In Summit ‘23!
(0:59) An introduction to Gene Therapy
(2:18) Three eras of modern medicine
(4:49) Living medicines
(6:35) Congenital blindness and other rare diseases
(9:37) Gene therapy applications for broad use, including cancer
(12:00) Immunosurveillance and immunotherapy
(14:44) Brain cancer test
(16:34) DEC2 mutation to reduce the need for sleep
(17:45) Gene therapy for people living on Mars
(18:40) Bestie Q&A: FDA hurdles and aging as a disease state
(21:16) Biotech’s valley of death
(23:52) Night vision and other human enhancements
(26:32) Fundraising
Follow Nicole:
/ nicole_paulk
Follow the besties:
/ chamath
linktr.ee/calacanis
/ davidsacks
/ friedberg
Follow the pod:
/ theallinpod
linktr.ee/allinpodcast
Intro Music Credit:
rb.gy/tppkzl
/ yung_spielburg
Intro Video Credit:
/ thezacheffect
Relevant links:
/ sirenbio
sirenbiotechnology.com/

[@inboxflux6777]

Bro bring her in for a two hour podcast - this was awesome

[@elitepropertiestoronto2979]

Agreed amazing she should be a science corner regular

[@chrisbuddy87]

I concur. Would love to hear her thoughts on rejuvenation and new wave of bio-hacking

[@malifestro3319]

This one should have been longer. Please get her on the pod.

[@DarrLaw]

+1. So many questions she answered with, literally, 5-word responses. They should be 5 minute + answers!

[@garyhartwelldinmore]

We need Dr. Nicole Paulk on the podcast for an episode or two!

[@maxcoleman8528]

This sounds great. I'm sure nothing will go wrong.

[@samlloyd672]

NOTHING AT ALL. Trust the science.

[@teamspeak9374]

Discarding the whole night vision superpowers bs, if you are at stage 4 cancer getting injected with some virus that has the chance to cure you seems like a pretty good idea. worst case scenario you're going to die anyway

[@Mangini037]

Remember when TED was good? Thank goodness for this summit to learn new things.

[@AlEbnereza]

Most DEFINITELY bring her back on the Pod. Spreading the word on these efforts can’t be understated.

[@vankram1552]

After watching this talk, I want to take a leveraged short postion on this company

[@rendezone]

This was my fav. Talk and it was difficult this year to pick a favourite, her work is IMPRESSIVE

[@asafzilberberg6648]

Wow - wonderful.

[@kristiannelson1851]

Okay, adding my vote to have her on the pod for a full show. Damn Dr. Nicole is good! Also, I have to say how amazing it is that I can be sitting in my little studio, and listen to someone of Dr. Nicole's caliber speak for 30 minutes...for free. Absolutely amazing.

[@mattthompson8329]

Best talk of the Summit, not even close.

[@denilthomas1]

What an inspirational talk! You can’t help but be excited for the future of humanity when you hear talks like this.

[@kevinlanham4293]

Definitely had some pitch-like moments, but I don't blame her for trying to take advantage of the stage that she was on. Not easy to squeeze in any real data given the time constraints, the general audience and the ground she was likely asked to cover. I think I saw her on another panel back when she was still at UCSF, maybe at ASGCT. Unfortunately, she didn't really address the shortcomings of AAV that Chamath tried to bring up. Felt like a dodge to me. Just say, "It has some limitations like a small payload and poor cell specificity, but these can be addressed by using mini-genes or dual vector strategies and capsid engineering. It also has many strengths, and is well suited to target multiple diseases, as evidenced by current FDA approvals, including the diseases that we are targeting." Granted, I have the luxury of typing this on KZbin and she was up on the stage seated between Friedberg, J-Cal, Chamath and Sacks in front of an audience. I probably wouldn't have been as eloquent. I am glad she circled back around and acknowledged Friedberg's question about the manufacturing bottleneck. It's a big problem, particularly as the field moves to treat larger patient populations and conditions that need larger dosages than required for disorders of the eye.

[@85oceanic60]

This is bananas and absolutely incredible. What a time to be alive

[@krissn8111]

This lady is amazing. She knows how to sell her stuff leave alone being genius.

[@knowledgelover2736]

Awesome. I worked with bioreactors and separation in my Chen eng degree back in 2005. Oil and gas paid better and didn’t need a PhD.

[@dylanc1925]

Would love to see and hear more of this in long form on the pod instead of weekly current events… maybe 1-2 a month would be nice. We have lots to learn from these brilliant folks

[@duvaughn5543]

Best in class. By far and away my favourite lecture so far. Bravo Sultan.

[@hineinindeinsein3362]

We need to make money with healthy people. Think about what she says. We need such a summit for energy healing.

[@willieposey2672]

This was so amazing cannot wait to hear her on the podcast in more detail

[@tgwashdc]

Engaging and delightful to hear from Dr. Nicole Paulk. A single prompt starts a cascade of pithy responses, vow! Thanks, All-In team.

[@flwi]

If you can encode logic in the medicine the term "stomach bug" gets a whole other meaning 🙈 Great talk! I'd like to hear more from her. She explains stuff in an easy digestible way.

[@value_investing]

As a scientist, I am very sceptical for her claims. But I also understand that she sure knows who are her audiences. Great show BTW.

[@curtinity]

Incredibly impressive! Thanks for sharing, deeply appreciate

[@HelloFellowAI]

That woman is absolutely on fire 💥

[@dsalz_]

I love her

[@johns.777]

Thanks besties!!

[@MickLeonardJD]

More, more, more. And Thanks!

[@carlosoviedo5685]

no i'm speachless wow

[@MrFredericandre]

I tune in for the All-In music

[@Markinthemix]

Enjoyed this so much! Phenomenal preso.

[@benditovicentecosta1710]

Chamath never disappoints man, and Friedberg is the man...

[@Doomlaser]

Great presentation. Modern medicine is a human-made miracle

[@jaycolucci5989]

Wow!! Awsome presentation, please have Dr. Paulk on again in the future.

[@Gamegenio]

This is my favorite presentation of this summit

[@canoepolomattyp]

That’s the best.

[@josh_wags]

So good

[@karolpelc3956]

She’s just amazing!!

[@SM-mz1ny]

Fantastic! Really loving the science corner talks

[@srikarravulapalli]

Thank you thoroughly enjoyed

[@eddiemeese1218]

Phenomenal presentation!! Wow!

[@canoepolomattyp]

Get her on the pod - she makes the future sound bright. We can all get behind that.

[@adamh0319]

Love her energy..

[@20thcenturyboy85]

Thanks for this optimistic guest

[@benditovicentecosta1710]

This was the best biology lesson, I ever had

[@yjwang3558]

Incredible talk!

[@Ivelin]

Incredible talk.

[@realestateattorney]

Amazing presentation!

[@valandil86]

This was freeking awesome!

[@Boboche]

What…more awesome interviews?! This is a monday even Garfield would love ❤. Many thanks!

[@jhunt5578]

I should be sleeping right now, would love that 4hr sleep gene edit.

[@GregBman]

I don’t know why this didn’t get more views! The implications for curing disease are gigantic.

[@Khanfuzed1]

Rhythm was off a bit. Nicole/her platform are very impressive

[@knkootbaoat6759]

I'm not saying this is the cause (ie correlation != causation), I just noticed (correct me if I'm wrong or you disagree) there is a negative correlation between All-in video views and female present in the video (thumbnail). I would say it's those people's loss for not viewing the videos because this video is one of my favourite all-in video and Mar Hershenson last year's was one of my favourite videos as well. I'm curious what others think.

[@marcagray]

People generally don’t care about the future until it’s here.

[@GodofDisco]

More likely it's cuz this one is only 30 mins @@knkootbaoat6759

[@Khanfuzed1]

@@knkootbaoat6759 there’s definitely something there. Personally i think she was toeing the line of woowoo and a bit too, i guess, unordinary with presentation. I cant wait to learn more, but with a least a bit of expected misogyny from viewership those kind of things will cause more unfounded negativity

[@jhunt5578]

If a person had the HDEC2 gene therapy for 4 hours of sleep, assuming they’d live to 100, that’s ~16.5 extra years of conscious life gained. Not to mention the health benefits from not being sleep deprived. If everyone got that therapy it would also boost the economy due to increased productivity and consumption.

[@itsjaynguyen]

Been waiting for a cure to my blindness in my left eye 😢 less goooo

[@whalespurtsoddengrass475]

They already have the cure for you ready. They want to make it legal to sell it to you first. That's why you don't have it yet. That's what this whole talk is about. Once you understand, you will see our civilization is mentally ill, unethical, and selfish to the exclusion of rationality. You deserve better.

[@hm25636]

A good talk! Very smart woman

[@moilanea]

I'm getting Elizabeth Holmes vibes from her.

[@djg450]

Great Job Sacks!

[@otaviopmartins]

Awesome

[@BertoBills]

I want to hear more of this. This was too short

[@meetrichardreyes]

Wow! I’m excited for the future. I wouldn’t mind having night vision 😎

[@RHt09]

As somebody who invests heavily in these companies (and has a background in biology) and watches a lot of these CEOs speak, she strikes me as a more concerning Elizabeth Holmes type. If you want to know what reasonable gene therapy researchers sound like, listen to Jennifer Doudna (Nobel prize winner and co discoverer of CRISPR)

[@theresanarasimhan5911]

Was thinking the exact same thing. She presented this science in a very twinkling light and completely left out any drawbacks and serious challenges to this area of science. Very delusional presentation.

[@RHt09]

@@theresanarasimhan5911 Definitely. The references to being able to easily modify out the need to sleep long hours and do a lot of gene edits with the tech we have right now is definitely divorced from reality. It took over 5 years to get exa-cel to the point that it can proven to work in humans safely and be presented to the FDA for approval. And that's a simple knock-out edit. We have no idea what genes are involved with sleep and how complex they are and what types of edits would be involved. I'm sure she doesn't know either. We also don't know what the ramifications might be from making these edits. Crazy claim to make.

[@shitmypants5275]

She talks about the potential market size lol I smell greed

[@taijistar9052]

Her mind moving so fast, speaking so fast!

[@FeroxX_Gosu]

Long #CRSP!

[@adamh0319]

Hey fabulous 4.. get this dynamo on for a long segment. This is next level interesting

[@joedirnfeld]

She is a doctor, wow wow

[@dbeck_youtube]

Major Theranos vibes

[@chukwuemekaallison4891]

When she said improving the human gene with viruses, my mind kind of brought up umbrella

[@YASH-xo9sl]

All IN guys done awsome job not just focusing on hot sectors like fintech crypto but other sectors like Bio-Tech and damn Dr. Nicole Paulk is freaking awsome speaker explaining super complex biology to someone who hates it !

[@barryonthefly]

I’m so glad there is no downside to gene therapy

[@db07c7ec7]

exactly, and wonder why no one ask the million dollar questions, the ethical view on the smart gene etc.

[@yumedan]

😂😂😂😂 Hit the nail on the head. All our troubles will soon be gone just give me your money please...

[@user-dj8gt6ik7c]

gene therapy causes cancer because you’re putting foreign genes into your body and your natural immune system reacts to that.

[@essiotll]

Most excellent! Also, this gives me a flashback to about 2005 watching OG Ted talks and seeing Craig Venter introduce human genome editing with CRISPR - these have a great OG TED vibe - with more entrepreneurs and more open discussion at the end.

[@jeffcal007]

The "OG" Teds were great. As stated on the All-In pod, the summit was formed to bring back positivity because Ted has now turned into a platform for social warriors.

[@essiotll]

@@jeffcal007 Indeed.

[@jamesdeininger3759]

The Q&A reminds me of the villain’s hubris in a Marvel movie, right before their experiment goes wrong 😂

[@jaggol9416]

I think this one was the highlight of the conference, not Bill Gurley's talk (don't get me wrong, I thought Bill Gurley's talk was amazing too).

[@mikescheme]

Any path to setup shop in Cuba or elsewhere to get this ball rolling quicker?

[@PaulHallelujahMaranatha]

Please bring David Sinclair, expert in anti-aging onto the show. His work is extraordinary

[@bernios3446]

Not sure if they can be compared. David Sinclair also conducts experiments with mice and says they have fixed blindness in mice, but somehow I do not trust him fully. In general people who present their research obviously tend to overstate the state of their research.

[@PaulHallelujahMaranatha]

@@bernios3446 he is clearly being suppressed by trad pharma. I attended medical school for 4 years

[@luisfernandosantosmora1000]

Sometimes it's just more efficient and safer to eat the leaf!

[@wendygu3469]

AAv delivery has not achieved tissue or cell type specific precision. Most disease are polygenic, meaning not a single gene mistake caused the disease. She is way oversimplify the complexity of disease biology. Perhaps for the layman finance audience. Sounded like a found raising pitch😂

[@diazigy]

Seriously, out of the 12 major AAV serotypes and sub variants, tissue tropism is barely selective. AAV is too small to deliver large genes. Production is super complex and needs major purification. Something as simple as titering assays to determine dose have huge error bars, like 80% relative standard deviation. There are several FDA approved AAV gene therapies, but only for rare diseases and cost like $400,000 per dose.

[@leejohn9754]

This is not enough. I need more. He needs to come back at least one of the two hours❤

[@ombasnet3488]

EDIT, CRSP, PACB, ILMN will be big soon.

[@ghtybn1372]

does anyone have a link to where we can get the "where are we now" graphic at 8:50 ?

[@Kenneth_James]

Everyone has at least heard of gene therapy Nicole. She's so animated. Exciting topic. Exciting times are ahead if these non-disease related treatments are given a regulatory green light.

[@willowdesk]

I wish these were 1 hr instead

[@carlosoviedo5685]

where you can have access to this types of treatments? i mean the ones that are already aprove

[@enteyedos]

BEST Talk of the show! Chammi shaking the arena as a PRO like always! Jason get OFF-WHITE now!

[@skyfireavenue2016]

Major theranos vibes. Wish I'm wrong though

[@hayato5115]

I wonder if we will be able to make a specefic body part larger...

[@shubhamdhiman528]

Can someone link the industry prospectus at 8:40? Can't seem to find it online.

[@alexwillenbrink8069]

30 years to gene therapy augmentation lol. I wish her research the best but there's no way in hell. Until we have absolute control over the adaptive immune system, we're extremely limited in our capacity to move forward on stuff like this or gene therapies that correct normal diseases. Not to mention all the other hurdles she mentioned regarding adoption by the FDA.

[@9spr]

I only work adjacent to this field so definitely don't have the full in and out picture of things but day to day I've seen many of these working their way through the clinical trial process. Additionally there's several that have already made their way through approvals including several cancer and eye sight treatments. There are serious safety standards that these treatments need to treat for and test for and rightfully need to achieve because these are serious and in many cases permanent changes being made but there is a lot of work being done here to make this happen. so regardless if it is the next 5.10.20. or 30 years This is important work being done. Although that's just my opinion,

[@alexwillenbrink8069]

I mean sure @@9spr. Ultimately though a lot of what she's doing is raising funds. Seems a bit unfair to set expectations that are essentially impossible to meet. The eye and the brain are immunologically privileged sites, ergo don't have nearly as many of adaptive immune system problems. For cancer do you mean like ex-vivo CAR T? If so again able to get around immune system problems because making changes to cells outside the body. If you mean treating cancer via gene therapy in vivo, I'd love to check it out if you have a reference or an article on it.

[@Yahweh42069]

just declare a pandemic and you can roll out whatever gene therapy you want lol

[@vincenthus399]

@alexwillenbrink8069 I don't think that that's accurate. In Leukemia for instance, the first patients were treated 10 years ago with CAR-T cell therapy and 2 of them are still cancer free. There are 500 CAR-T cell therapies in clinical trials. It is likely these will translate into new medicines.

[@robertkelleyroth409]

My understanding is the AAV guys are using something like a directed evolution technique. So instead of naturally occurring AAVs they develop ones for particular types of cells (like brain cells). The rest of the idea is if you can increase delivery to the particular cells you can decrease the dose and therefore decrease immune response without sacrificing efficacy.

[@terrysullivan1992]

Running at .75 speed makes her much easier to listen to.

[@j03man44]

Literally unbelievable. As in i do not believe the claims made. There were no discussions of risks or tradeoffs. I would bet my net worth that there are major downsides to "naturally" sleeping 4 hours a night, for longevity if nothing else.

[@onsidelegal1002]

no discussion about MRNA failure??

[@chesstictacs3107]

As a gentleman, I would like to compliment her beauty as well. Since enough said of her intelligence 😁

[@John-wf5if]

When will cartilage regeneration be realised? I need new knees and hips.

[@arthureum]

This is how all zombie movies start. 😅 A treatment for the masses

[@fbmg8547]

Wow

[@ambarkumar7046]

She first needs to make something that will help her not stay out of breath while giving presentations

[@rashad5969]

@Lex Fridman needs to bring her on his pod, and let the robot to human conversation take place

[@DanyPell]

Give her the money if she can really do such bio engineering improvements!! The US will be able to defend itself!

[@Skankhunt420.]

5 to 10 years in science means 50 to 100 years

[@kitmburau]

Great work as always! I raise an eyebrow when she says "night vision is easy". Beware of those with more answers than questions. Assuming there will not be any untoward effects from manipulating the human genome....... bad idea. A negative side effect may be worth it when you are fixing a true genetic handicap such as blindness or curing cancer. When you are attempting to "enhance" the human body it would stand to reason that the average patient will not be willing to tolerate any negative side effects or problems since their aim was to improve themselves rather than downgrade things.

[@kitmburau]

Holy crap then she goes on to say she can "restore joy" and that mental health problems are usually single variables. The subjective nature of the human experience, sorrow and suffering, restored by gene therapy....... If despite access to current antidepressant meds depression rates in the US continue to soar it implies we still don't understand "mood" that completely. This is a gross oversimplification of the nature of many things. Yall should definitely have her on for two hours and have Friedberg ready to push back. I put her on par with the AI experts that say there is "nothing to worry about". They haven't thought hard enough about it.

[@dkgong]

I feel that she’ll either be the next Elon Musk or Elizabeth Holmes of biotech. Only time will tell.

[@NovellaDeParmesano]

Elisabeth 😅

[@birhon]

Can viral gene therapy be used for in vivo data collection?