April 10, 2024 • 38 mins
In this episode, Omri Amirav-Drory (NFX), Joe Betts-LaCroix (Retro Bio), and Alex Colville (Age1) discuss the history, recent progress, and hurdles in the longevity industry, including the evaluation of potential founders and business risks. The discussion further encompasses the global fundraising potential and societal impact of the longevity sector, viewing aging as a disease, and the future of longevity drugs.
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(00:05):
It's all great to be here today, speaking with2 of my favorite people, Alex and Joe, on my
favorite subject, longevity.
At NFX, we call longevity, the transition fromseek care to health care, Morgan instead of the
current state of waiting for somebody to getsick and playing a game of whack a mole with
the different diseases that manifests as we getold, why not tackle the root cause most
(00:27):
diseases, which is AG.
So let's start with a quick introduction.
Joining us today is a Jo from RetroviralSciences, and Alex from the age one fund.
So let's start with Joe.
Can you please introduce yourself and say a bitabout the company's mission?
Yeah.
I'm Joe.
That's the and CEO of retro Biosciences, whichis, sort of medium sized biotech startup in
California.
(00:48):
That's about sixty people now, and we are veryfocused on our mission of adding 10 years of
healthy lifespan to humanity.
Yeah.
I love the mission.
Always when we meet, I ask myself why only 10years?
I think that if we are successful in ourmission that I will be so incredibly proud of
(01:09):
all of us and that the impact on so many facetsof society and people's lives will be so great,
but it feels enough for me as a person.
Impact wise.
Yeah.
And we can always have stretch goals.
Great.
Alex, can you please introduce yourself and theage one fund?
Yeah.
Absolutely.
You so much, Andre, for having me on.
But my name is Alex Coeville.
I'm the general partner and co founder of age1, which is venture firm focused on longevity
(01:34):
biotech specifically.
So specifically focused on catalyzing andfunding very early stage companies that are
working to this goal exactly like Joe's amazinggoal of increasing healthy lifespan.
We don't put a year on it.
We're running we're on it.
Maybe that's less ambitious or more in I don'tknow, but what I do know is that age 1 in
essence came from the longevity fund, which myco founder Laura Deming made back in 2011 as
(01:59):
kind of the first venture capital fund focusedon the theme of longevity.
And we're super, super excited to haveintroduced age one last year and just to have
closed our first fund out of this new vehicle.
So, yeah, congratulations.
I know what drew me to the space, but, Joe,what drew you to longevity space?
I guess I went through a bit of a lifetransition I guess backing up, the only thing I
really know how to do is startups.
(02:21):
That's like the hammer.
And so I go around the world looking for nailsthat I wanna pound in.
And originally, it was doing things that werecool.
That was enough for me.
I think that's maybe it's a young person'sJames.
But then after succeeding reasonably well atsomething, well, I decided I wanted to make
something meaningful.
And meaningful to me means people becausepeople are special compared to, like,
(02:41):
everything else in the universe that we knowof.
And so of the things that are meaningful toPete?
Like, you know, what affects, like, people'slives?
Like, war, famine, poverty, displaced homes,all that kind of stuff.
Pretty much all that requires extreme politicalacumen, which I don't have.
I'm a nerd.
So, like, what can a technologist do of thethings that I could work on technologically by
(03:04):
far in a way the greatest source of humanmisery.
And therefore, the thing that could, if it wereeradicated, could create the greatest source of
human joy and thriving is dealing with disease,which sounds like a huge giant, you know, like
boiling the ocean kind of task, but thenlooking at disease, like just stacking it up,
like, what are people suffering from athospitals?
(03:24):
What is money spent on at hospitals?
It's like 85% age related disease.
It's not like I have to go around and, like,fix kidney disease and fix psoriasis and fix,
like, to fungus or whatever.
Like, all these diseases.
It's like, aging is basically it.
It's basically, you know, pretty much all ofdisease that we ultimately deal with in the
hospitals and so age related disease.
(03:45):
So that, that makes it more focusing for me.
Well, I should figure out why they happen.
What is this process called aging?
And is there some way by addressing thatitself?
It could make the biggest difference
That's great.
And by the way, it's always amazed me how thekind of the backlash we're getting in the
longevity space where some people say, oh, youknow, it's, the tech bros want to live forever,
or other people think, oh, I don't want to beninety year old for 50 more years.
(04:09):
And in my mind, what longevity is is juststaying healthy.
The best health care is to be twenty two yearsold, right, to be young and healthy for meal
longevity is staying young for as long as youwant and involuntary Right?
So that's my mission at least.
So, Alex, you're a scientist, now investor.
What made you Flint realize that this is whatyou want to spend your time on?
Yeah.
For me, it was kind of like the eight year oldmoment of watching people go through the worst
(04:34):
parts of age related disease.
And kind of seeing somebody go throughdementia, seeing somebody else go through
cancer and kind of starting to ask why.
And, you know, you kind of ask why a lot and,like, why there aren't more options to do
something about, like, how horrific both ofthose diseases are and how much suffering comes
with it and, like, it's just that game of whythat you, like, keep asking why, and it it's
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just, like, you don't really get the answer toyour question.
And, you know, people Beller you, oh, becausethat's the way it is.
Or, like, oh, that's life, that's aging.
That's just like what we deal with, and peoplekeep asking you why, and you just get more
frustrated.
And eventually, I kind of, like, sat with thatfor probably, like, 5 or 6 years pretty
silently, just like very unhappy about it.
And eventually that led to kind of late teensgoogling more about it.
(05:19):
And during undergrad James across through mygoogling this field of the biology of aging and
longevity biotech that we're here to abouttoday.
And that was when I was like, holy cow, foundmy tribe, these are my people, and haven't
looked back since.
Perfect.
It's a great segue because I really want totalk about the scientific history of longevity.
In my mind, one of the rate limiting steps forlongevity is a lack of scientifically valid
(05:42):
things to do.
Not a lot of things you can do.
And when we found one, there is a lot of energybehind it.
Right?
So it's so important, to discuss what's alreadyhave been discovered.
So, Alex, you've been doing research in thisspace for a while.
Age 1, I think, is the first longevity Pete,right, that's the name of your So can you
please talk a little bit about the kind ofscientific history of longevity?
(06:02):
Yeah.
So the scientific history of longevity is veryinteresting and, you know, it's certainly not
up to me, to determine when exactly the fieldwent from mythology to actual science, but the
answer probably lies you know, I think areasonable answer to it would be maybe sometime
in kind of like the early 1900 with the studyof calorie both done in model organisms and
(06:25):
also in humans.
And this kind of eventually led to the work ofLeonard Heyflick and Lenny Hey life, in
essence, he worked a lot on telomere biologyand kind of showing that cells in a dish do not
divide indefinitely.
There's this in essence, distinct replicativelifespan in a dish, and I think this was very
(06:45):
transformative to people in terms of realizingmaybe the limits of aging or what may be, you
know, a distinct part of the aging process.
And then, you know, pretty much in kind of sameera of a decade or so later, we got to see the
very first quote unquote longevity genes,which, yeah, you're spot on age 1.
It originally came out in a paper from MichaelClass.
(07:08):
I think it was 1983, and it came from anunbiased screen in worms where they, in
essence, gave worms a mutagen that caused abunch of single gene mutations, and they ended
up getting, I think, like, 8 or 10 strains thatwere long lived out of that, and they didn't
realize until kind of subsequent follow-uppapers, but eventually they were able to
characterize that I think all of thosemutations were a part of age one this gene that
(07:32):
was shown to be kind of the first to increaselifespan and increase lifespan in the worms by
about 50%.
And then this eventually led to a secondlongevity gene down to from Cynthia Kenyan's
work at UCSF.
She several times called it the Grim ReaperPete, and this kind of eventually led to more
of this modern field being able to study kindof single gene mutations and look at their
(07:54):
effect on health span and lifespan.
Cool.
I guess the question is what range, right,because, you know, people ask me if somebody
interested in longevity, what should I do?
Right?
You know?
And I think even 5 years ago, what I would tellpeople is, you know, don't die from stupid
things, you know, drive carefully, you know,eat well, sleep well, exercise, but other than
that, there was nothing really to move theneedle.
(08:16):
Has something changed in the last 5 years that,you know, you're excited about?
I'll start with Joe again.
I think as a secular trend, 1, we're justgetting a lot better at biology in the last 5
years, and we're made of biology.
And aging is caused through biologicalmechanisms.
And that just makes it faster to figure outwhat's going on and how it works.
(08:36):
And 5 years has been a really meaningful time.
Like, people started doing single cell.
Like, I think single cell was one of the mostsignificant steps forward in understanding
biology.
Before that, people thought of, you know, therewas this epic moment of sequencing the human
genome that happened in, you know, 2001 ishRight?
But it turns out that all our cells are notexactly identical.
(08:57):
We seem to be composed of all these differentcells that are doing different like skin cells
and brain cells and germ Beller.
And getting to the point where we couldactually look at our tissue as an assembly of
this rich extremely diverse multi interactingassembly of all these different dozens and
hundreds of cell types.
I think that picked off another inflectionpoint.
(09:19):
In bio.
As far as I like just, I have observed it.
And, you know, we started doing single cellsequencing earlier, but it seemed like roughly
within the last 5 years, I think thebioinformatics have started to catch up.
You know, because there's this interplaybetween kind of, like, people making tools and
then people figuring out how to use the toolsand learning a much about the biology or any
science in general.
And then the toolmakers think saying, Hey,there's some new stuff in making new tools.
(09:40):
And, you know, there's these cycles that goback and forth.
And I think in the last 5 years, people reallystarted figuring out how to make a meeting out
of the data that that single cell sequencingtool was generating.
Now we're seeing a rush of new machines beingbuilt.
Then they have to catch up and figure out whatto do with the data and so on.
I think that's been the biggest trend, butthat's just a sort of a general biology trend.
Then I think in terms of the aging field, Oneof the things that happens when you're watching
(10:03):
from afar in any given overall exponentialprocess, like, I think things sort of get or
steam with time First, it's just a few kind offringe researchers, you know, like, throwing
mutagens on worms.
They're interested in aging.
One here or there, people saying what if in avery open minded scientific way.
And then there's another one, and, and someoneelse reads their paper a year later and thinks,
(10:23):
okay.
That was a pretty disciplined scientificallyrigorous way of studying this.
I guess I could do that too.
This isn't all just like, you know, liveforever religion weirdos that don't do real And
I think more people read those papers and morepeople get involved.
And that's an exponential process, you know,more than 2 people read a paper.
And so I think that this field has been takinghold as a rigorous and legitimate scientific
(10:44):
endeavor exponentially.
If you're looking at it from an outside linearpoint of view on an exponential process, tends
to look like nothing's happening.
And then all of a sudden, something'shappening.
You know, there's this elbow in the curve.
And I think that's where we are right now.
We're at the point where this exponentialprocess is starting to make a linear dent in
all of bio academia.
And then usually academia kind of startssomething and says, hey.
(11:06):
This is possible.
But look at these phenomena, and then businesscan then jump in afterward and say, Wow.
Yeah.
It's possible.
Let's make it actualized for Pete.
Yeah.
For me, I have to say my excitement for thespace always started the science behind the
space, always started with just basicunderstanding of the rule of nature, like
nothing in what we are trying to do doesn'tinvalidate the rules of physics.
(11:28):
Like, it seems like we should be able to solvethe problem, and I just gave a token.
Conference.
And I started it by staying 1st Nature solvedaging.
Right?
If you think about an AT or old, we can have ababy with forty year old, then that baby will
have the same lifespan as a baby boy to 2teenagers, right, that you're something magical
about nature.
Otherwise, we won't exist that Joe mightdisagree, but when you zero everything out,
(11:52):
when you start with an embryo, you kinda resetlifespan.
Right?
It's kinda magical Otherwise, we won't exist.
Any species would exist.
And the second thing I'd like to say is humansfor aging.
When you think about aging of our cars or ourbuildings, how we solve the aging for cars, we
just keep replacing parks.
So the basic, I think, can be solved.
Like, there is nothing in what we're trying toachieve that is impossible.
(12:15):
We just need to find some typically valid waysof doing it.
And that takes me to the state of the art.
Right?
You know, Alex, you're investing in the space,So to move things forward, what would you
consider as the most cutting edge topics in thespace right now?
Yeah.
I think probably along those lines, because Imean, in part what's so funny is, like, well, a
lot of the things that we're so excited abouttoday, scientists and folks were very excited
(12:36):
about in the 1990s.
For example, and, like, the whole notion ofreplacement parts or, you know, being able to
target biological pathways that slow or preventthe rate of aging more broadly.
Like, both of these, were, you know, extremelyhot topics of discussion in the nineties.
Amongst among the among the very nichescientists in this community.
And so then it's like, okay.
(12:57):
Well, why the heck are, like, now we're, like,still just as excited about it and yet feel so
much more just defied in our excitement aboutit versus them.
And I think it really is, like, the progress oftools and the basic science behind these
things.
And kind of to segue into your question of,like, you know, a cool example is, you know,
the fact that, you know, back in the nineties,everybody's talking about this ability to have
(13:17):
a replacement part and, you know, you give thisreference to the car and, like, this was
something actually that Len Hayflick talkedabout a decent amount where he was like, oh, we
actually haven't solved aging in car becauseyou can only replace parts for so long before
the car still fails to some point.
I mean, what's so interesting from like thehuman version of that is, you know, we wanted
replacement parts back in the nineties, peopletalked about it, and people talked about it all
(13:40):
throughout the early 2000s in terms of havingthe ability to place a cell in the human body,
and we really weren't able to actually feasiblydo it and show that we could do it in humans
safely and effectively until the past 3 yearsor so.
And this part is really remarkable to me.
And then it's a question of, like, what changedto enable us to get to this place where we
actually have the ability to have like celltherapies that are, you know, derived from off
(14:04):
the shelf that we can, in essence, put inhuman, and they'll long term survive and
engraft and kind of serve a useful purpose.
And in part, it was like Shonya Yamanaka'samazing Nobel Prize winning work around Beller
reprogramming.
In part, it was on the boat of a lot ofscientists who had to optimize the process of
kind of differentiating cell types from IPSCs.
(14:24):
And in part, it was just a lot of people whomade all the other sort subtle optimizations
that needed to happen from a deliveryperspective and otherwise to, like, get the
conditions just right to show that we could doit with just a couple of cell type And, you
know, the evidence and reward of this has beenwe saw just a couple weeks ago, a company in
the Parkinson's disease space that was inessence able to show that they could take these
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cells derived off the shelf and Flint them in ahuman Parkinson's brain and and show that they
could survive and and have function for up to18 months in humans.
And so, like, yeah, this is an area I'm justabsolutely incredibly excited about.
That company being Bluerock Therapeutic withseveral others working in that same space and
showing some really cool preliminary evidencein humans.
Like, are we actually at that point that we cannow replace any cell type in the body?
(15:10):
Right?
And then, like, what could get us from now tothat goal?
Or, you know, likewise with human Morgan, alsoinsanely excited about that right now.
As, obviously, you talked about partialreprogramming.
Joe, I think your company is known to beworking in that space.
What drew you to that specific modalities?
I would say a ex sizes, like the things thatpeople talk about in the longevity biotech
(15:30):
space.
You know, there are these molecules that youcould take, for instance, metform.
And, yeah, it seems like it probably slowsaging.
If you give it to mice over long periods oftime.
They'll live, like, 10% longer if you give themmetformin.
But I have this kind of impatient entrepreneurblood in me that I like things that are fast
moving and make big changes.
And the phenotypes that I saw in thereprogramming literature were just huge.
(15:55):
You know, you treat these animals for arelatively short period of time and then the
shifts and the Morgan of aging characteristicsof their tissues of various kinds were quickly
changed.
You know, animals had improved memory outcome.
DNA had less damage, a pretty wide range ofdifferences across tissue and quickly induced.
So I think I would rather work with somethingas an entrepreneur that's kind of like a bit of
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a wild bucking bronco and kind of learn to tameit and to coax it into a particular direction
than to take the sort of slow worn out mule andtry you're, like, girded into action.
It's just more exciting for me as anentrepreneur.
So it's a founder.
What do you think your product will be in theend?
Will it be small molecule or antibody orwhatever modality that will slow down aging or
(16:41):
will be something old people take to rejuvenateand to be younger, what do you think your
product will be in the end?
I'm definitely biased toward rejuvenation overslowing aging.
You know, at some point, probably I have toacknowledge a bit of personal bias too.
Because, you know, if I were in my twenties, Iwould probably wanna be at developing things
that I could take over the whole course of mylife and slow me down, but I'm older than that.
But it's not about me I just like to be able toacknowledge my viruses if they do exist.
(17:03):
So we're not a single product company.
We're a single mission company.
I have 5 parallel research teams working ondifferent aspects of aging, different
modalities.
And they have different intervention methods.
So we have a small molecule program.
Our atrophage group.
We have 3 different cell therapy programs.
And then another one that's basically genetherapy program.
So a bunch of different products, and a prettyintensely product oriented.
(17:25):
Like, we are not academia.
We make products for people to take and maketheir lives Beller, but I'm not focused on any
particular modality, like a therapeuticintervention agnostic.
But how do you get it approved?
Suddenly aging is not a disease.
That's what the FDA said.
Need to get approval for a disease.
So how do you get approval for rejuvenation?
Yeah.
Funny.
I was visiting Japan recently, and but theprime minister was interesting.
(17:47):
In Japan, you you can put that someone died ofold age under a certificate.
And I'm kind of interested in the conversationthere that if that's true, then theoretically
you should be able to make a therapeuticprevent that cause of death.
Right?
So I wanna continue that conversation in Japan.
However, right now, I'm in the US, and that isnot a thing.
Aging is not a disease or a cause of death.
(18:08):
So what we have to do is use what I call proxyindications, which means that diseases that are
caused by the same mechanism that we're workingon, but that typically are more acute or
there's a more kind of immediate need,preferably in unmedical needs.
And the ones that, you know, there's anexisting ICD code Morgan that, you know, you
can actually get an approval from FDA to marketa drug for that.
(18:32):
So that's basically every single program has tohave one of those.
And then the idea is that we deliver onmedicine for a proxy indication first, and that
establishes the mechanism is functional andpeople that gets the therapy out there can
establish a safety track record for it.
And then for open minds and doors, to beingable to expand into larger indications.
(18:53):
And then I think this should be the ultimatepath as you alluded to Currier, Umadi, for all
medicine.
Ultimately, it should be able to be usedpreventatively
yeah, the best health care is to stay healthy.
As I like to say, interesting what you saidabout Japan and dying from old age.
I think in the US, they call it naturalreasons, right, know, natural causes.
And I think there is nothing natural of dyingof old age.
You know, natural is dying when you're 22 frominfection.
(19:16):
Know, and and we don't call it natural today.
And I think, in a 100 years, looking back,dying at the age of seventy from old age will
be looked very primitive and very sad thing.
Beller, let's talk about investment and howinvestors Pete the longevity space.
You know, my day job is general, permanent, andeffects.
A big seed fund.
You know, we take money from LPs.
We invest in companies.
(19:37):
We need to show returns.
And the reason we like longevity is, a, wethink it's the biggest market.
It's for everyone, be it's very magical.
Like, if you really invent something thatrejuvenate you and make you younger, like, who
won that.
And it will be totally magical defensible thingto do, and it drives the most passionate people
to the space.
So you get the best founders.
Like Joe.
So maybe Alex, you know, you're a investor likeus.
(19:59):
So what's the framework that you use toevaluate companies in the space?
Yeah.
Well, obviously looking for Joe's, I don'tknow.
Maybe we should need to clone more of him.
That's the easiest solution, but I can do it.
I can do it.
I have a company for that.
In essence, like, you know, I think there'skind of like the 3 things that I'm constantly
thinking about with potential founders, whichis just like, one, do they have extraordinarily
(20:20):
high judgment and like ability to make rightdecisions to our, you know, as at least
somebody on a founding team mission aligned tothe aging fields and the long term goals of the
field.
And 3, are they willing to be a founder?
Kinda like think on those 3 James as of, like,evaluating potential founders or potential
talent that, you know, are the kind of nextgeneration Joe's that kind of help push the
(20:43):
field forward.
And that's kind of like the immediate accessthat I'm evaluating.
I think at least at age 1, we take a super kindof founder focused viewpoint, and that kind of
under that first bucket of like a founder'sjudgment.
So many other of the standard kind of VCevaluations come into the picture, right?
Because, like, how do you evaluate somebody'sjudgment?
Well, I wanna know, like, how they view Pete tomarket, how they view science in a specific
(21:09):
area who they can attract to, you know,associate with from a, like, scientific advisor
perspective.
Kind of, like, what is their ability to, like,run through walls to make that happen?
And so I think, like, all of those kind of foldinto this bucket of, is this agent company
investable on, you know, adventure scale, like,7 to 10 year timeline, right, that kind of fits
(21:29):
in that higher order framework, which I thinkit really comes down to, like, just a founder's
judgment.
Cool.
So you talked a lot about fathers.
Obviously, funnels are very important, butlet's talk about a little bit about the risks
of longevity companies.
One of them is something that Joe justmentioned.
Right?
The FDA still don't recognize aging as adisease.
You need to find an adjacent indication.
(21:49):
I call it take longevity indications because,you know, some people go after osteo for ease
of the knee, and they don't develop a drug fortougher raises.
You develop a drug for aging that might alsohelp with the stopper raises, but might not be,
you know, the best efficacy for that.
Right?
So it's harder to get approval.
What other risks do you see for companies thisspace?
I think losing your way.
Losing your way is a risk.
(22:10):
I think it happens to people in any kind ofmission focused situation.
This isn't really the full mission, but it'spractical for us to work on in the short term.
And then they focus on that forever, and theynever kinda make it I guess that's more of,
like, getting back to, like, personal founderrisk.
But it's something that I constantly repeatback, like, if we're in strategy sessions,
which we do twice a and I'll constantly bebringing back up.
(22:32):
Yes.
We could go that direction, but I think itwould take us off track, and we need to keep
moving our focus back.
Even if it means we face more risk of certainkinds are less immediate reward, it's worth it.
And we're in a privileged position of havingpatient capital, like just our investor, I
guess, the equivalent of your LPs have areasonably long term view.
I mean, also, personally, from a founderperspective, impatient, and obsessed with PACE
(22:56):
as MI.
A really hard problem.
And I think one needs to think on longer timescales to get there.
Like, I don't necessarily think that we'regonna hit our entire mission within 7 year
venture time frame.
I believe we'll make a dent.
For sure.
We'll, for sure, ship our first drug and thenour next one.
And then our next one.
And then I got next eventually, we'll hit ourmission.
I guess there's business risks.
Like, one thing I see happening over and overagain in the biotech industry, and it makes me
(23:20):
sad is that you see a lot of companies startoff with toward a mission, with a particular
discovery platform and really believing in thescience and the power of the science and in the
depths of their pipelines.
We have this platform.
It's a novel way of discovering therapeuticsagainst particular, you know, set of diseases
or whatever.
And then gonna be able to generate, like,dozens of cures for all these things.
(23:43):
And they get one thing that's kinda startedheading for the clinic.
They derisk certain aspects of it, and theystart running out of money.
And then they go talk to investors, and theinvestors like, I don't know about all this,
like, kind of, like, nerdy stuff.
The, like, the sciency discovery stuff with allthose Pete, like, I can't quite figure.
I don't really understand it that well, butthis drug that looks like it's about to go into
(24:04):
phase 1, that makes sense.
I see the business sense of that.
So I'll invest into that, but you have to layoff your discovery team.
So you see these companies constantly start offmore optimistic and idealistic.
And, like, I guess I have a bias toward deeptech, I guess you would call it.
I mean, that's the buzzword in the investmentcommunity.
But I believe that the important changes thathave happened throughout human history credible
(24:28):
lifestyle today have been from not so muchfrom, you know, just like figuring out that we
should have curbs be 6 inches high on thestreet instead of 8 inches high or whatever,
but have been more like putting in theirresearch and figuring out how to make a really
good rocket engine or how to advertise cloneDNA, etcetera.
And so it said to me to see these organizationsgetting deep tacked over and over again.
(24:50):
That's kind of a business risk in a way it'sinspiring to me when I see a company starting
to do well in the investors.
And I guess they've done a good job atcommunicating with their investors and helping
share the vision not only of this first item,but their whole pipeline and the thesis behind
it, and they can keep R and D funded.
Yeah.
The only thing that matters, if you look backin history, the only thing that matters is is
(25:11):
science and technology.
Everything else is just games.
That's the only thing that moves productivityand the human condition forward.
I think we all agree on that.
And let's talk a little bit about thefundraising side because all of us had to
fundraise for longevity.
So, Alex, you had to fundraise from LPs toraise your fund and Joe, you had to fundraise
from other funds or angels to raise money forlongevity.
(25:31):
So, Alex, let's start with you.
You'd think that every person with money, ifyou scratch him, you know, he's a longevity
buff.
He wants to be healthy and live longer.
Was it easy, or was it hard?
How was your experience?
Raising money for all this fun.
Yeah.
I mean, I think I don't know if there is evereasy fundraising unless you're maybe, like, a
machine learning company or something atSilicon Valley these days.
(25:53):
I think almost any fundraising is hard even in,like, the easiest of circumstances.
So I'd say it was, like, way easier than Iexpected, but I also expected to be swallowing
glass for a year.
And I would say it was like a slightly morepleasant experience than that, but it was
definitely a year grind of just making ithappen even though it was a pleasant
(26:16):
experience.
So in essence, what was the experience?
Like, yeah, I mean, I think I found out, forexample, that, like, through some global
travels, people now just when you mentionedlongevity anywhere kind of outside the they
just think of Brian Johnson, and they ask youif that's what you mean by the longevity field.
So I've learned kind of how global the field isgone and turn of getting name recognition in in
(26:36):
terms of exactly kind of how that process goesand kind of people's comfort with the field.
I mean, I think people do start to see it asone of these opportunities that they need to
track.
And even a lot of the more standard, Beller,traditional funds It's on their radar now.
Maybe not as something that they're activelyinvestigating, but it's at least on their
radar, which I think is a crazy difference.
You know, I think back just 10 years ago, 11years ago to Laura launching the first fund out
(27:01):
of the longevity fund vehicle and, like, howhard that must have been to a approach people
for an industry that didn't even exist Pete.
And now we get to sit here with a luxury ofsaying, you know, there's, you know, what,
like, over 180 different companies in thisspace, and people have heard about it for
better or worse, sometimes in either direction.
So I think that's a really cool change that'shappened in the fundraising landscape is just
it's more on people's radars than it's everbeen before.
(27:24):
Yeah.
I think we all agree that longevity might notbe the best names.
I think there's a big vandaigram of peoplethinking about longevity.
What does this mean?
Some people think it's screams.
Some people think it's extreme biohacking likeBrian Johnson.
I think we're in the camp of, like, the deepscience, you know, rational thing that can move
the needle and, you know, prevent diseases.
I think that's the camp that we're if I cangeneralize, that we're all in.
(27:46):
But I want to talk bigger about the businesscase for longevity.
Right, because, you know, not only it's thebiggest market in the world, I'm about to write
a blog post about the business of longevity.
I wanna call it longevity, the l in LTV.
So LTV means lifetime value.
Right?
So in my hypothesis that not only everybodywould to have the longevity drug, but it makes
all other markets better because it increasesthe lifetime of your customers.
(28:10):
They just live longer to consume whateverproduct or service you grading.
Somebody made a business case for, you know,the economic value of adding 1 healthy year for
adults in the US.
It was suffering in the trillions of Beller.
So, again, it's so surprising why there are nomore investment in longevity than they are.
So, you know, Alex, like, why do you thinklongevity companies are great businesses to
(28:32):
invest in?
Yeah.
Like, in part, like, some of the biggestreturns and, you know, examples or areas of the
best financial returns ever seen are kind of inareas where historically the opportunity has
just been completely overlooked and you havemassive, massive markets at play.
And I think that sums up the longevity space toa tee.
We wrote a blog post about it probably like 3or 4 months ago just in terms of the, like,
(28:58):
possible market that's achievable with the 1stFDA approved longevity drug.
And, you know, we included, it would be about a150 to $200,000,000,000 per year in annual
revenue.
So this would be in essence 3 to 4 times thesize of the entire market of GLP 1 receptor
agonists, your Ozempic Wagovi, that Munjarothat has been, you know, totally transforming
(29:20):
economies of European Countries.
Like, if you look at the growth of NovoNordisk, just becoming like the most valuable
company in Europe, I'm pretty sure.
Right?
It's like and that's you know, a third or a 4thof the size and magnitude of the effect that
the longevity field is going to see anexperience.
And we just know that that's gonna be the Themarket poll is there, it will happen is just a
(29:40):
matter of when.
So I think you're spot on.
I'm super excited to read your post becauseit's the massive market that's involved in the
very few shot that have been actually taken toachieve that market.
It's a huge mismatch in terms of shots on Peteand the rewards for scoring.
One of the challenges space has is the proud tobe in a space that has this category.
This this is is characteristic, but there is alot of sort of external value created And what
(30:06):
I mean by internal and external is there's asystem in which the investment is made and the
product is produced and revenue directlygenerated from the product And then there are
the other effects on the rest of the world.
You can make, like, high speed race car orwhatever, and you can get paid x number of
dollars every time someone buys 1.
I don't know about the externalities for that.
You know, maybe it's just, like, incrediblyinefficient and cost lots of pollution and
(30:29):
noise and, like, people die often from themand, like, whatever.
It's like, maybe they make the world a littlebit worse place.
But, you know, you can categorize products thatway.
I think there have been really good Bellerreasoned and detailed carefully calculated
cases made for longevity therapeutics thatproduce them, and pretty much everything gets
better society wise.
(30:49):
The amount of time that you have to supportPete, there's, like, the younger population
support the older population that there's thissort of like ratio that has to do, you know,
it's like terrible in Japan and Korea rightnow.
You know, the retirement versus non retirement,how long can people work basically versus
that's a huge, huge effect.
People are healthier or longer and can remainproductive rather than being a burden to
society.
(31:10):
You don't necessarily get paid for that bymaking your longevity drug, not necessarily,
just effect on families, on a society, onproductivity, on forward progress.
And there are a bunch of things like that thatall ripple out from making good, healthy
longevity drugs that you don't necessarily getpaid for directly.
But I think there are enough still that and bemoney that flows back into the same industry
that produces them, which is a virtuous cyclewhere they can produce more such drugs using
(31:34):
that money, because it takes money to fuel Rand D, that there are enough that will still
incentivize people to continue.
This exponential growth?
Yeah.
Totally agree.
And, Alex, by the way, I think it's kinda funnythat you mentioned GLP drugs, like Ozempic,
etcetera, because when I look back at thebiggest pharma Pete in the last 5 years, which
is GLP drugs and even the COVID vaccines, in mymind, those 2 things are longevity drugs.
(31:58):
It's things that you give to healthy Pete, sothey won't become disease, right, you know,
overweight take that drug.
So you won't get NASH.
So you won't get diabetes.
Right?
So you you won't get heart attacks.
So we see the value of those drugs, and thoseare the biggest drugs categories ever.
It's something you give to everybody to keepthem healthy.
So, yeah, I think the business case has alreadybeen made by other drugs, but now let's attack
(32:21):
the root cause let's talk about the future andkinda advice for founders.
Let's start with, what do you think the longterm society effect will be if this space will
be developed as we think it will?
How the world would look different if we havethose drugs?
I mean, the easiest way to think about that forme is, well, how does the world look different
today from how it looked?
(32:41):
100 years ago when people lived shorterlifespans.
You know, it was life was, you know, nastier,shorter, and more brutish.
I think people will look back on now from thefuture and just be like, ugh, man, that sucked.
I'm sorry that people had to live back then.
I get it.
You know, I read the 20 century literature, andit's pretty brutal life.
And you don't know, you know, people are, like,dying of Alzheimer's and all these other, like,
(33:06):
fundamentally treatable things because theyjust I guess they just didn't have the medicine
then.
Yeah, so it'll be a little bit of sort ofgritty reality and a bit of Pete, probably
Yeah.
Definitely.
So we talk about vaccine.
You know?
So, again, you take something and you never getviral infection if we get better vaccine.
You know, you take GLP 1 inhibitors and you'realways fit and, sexy.
(33:27):
Right?
You know, you take partially programming creamsand you're skin looks young and you grow the
hair back, that's something that I feelpersonally about.
Yeah.
Like, some people hate their birthdays.
I always celebrate my birthday.
James a milestone, I survived another year inmy goal of living in the future because the
future is going to be awesome if, the companywe invested and the company you are working on,
(33:49):
Joe, will work out, right, because we'll havethe solution for all of that.
And I think some people are worried about, oh,it's going to go to reach Pete.
To that, I say an expensive solution is betterthan no solution, and expensive solution tend
to get cheaper over time.
You know, patent runs out and everythingbecomes cheaper and more accessible to
everybody Beller, and I'm excited about thefuture.
(34:09):
I want to live in that future.
Even if it's cost a lot, one of the sciencefiction books I read, the way they fund the
longevity treats is people saved instead ofsaving for retirement, they saved for the
longevity treatment that took them back toeighteen years old and they call it 2nd life
and 3rd life and one saying in the book is,life sucks, then you rejuvenate and do it all
over again, which is way better than our optionright now.
(34:31):
So, again, for both of you, I guess, samequestion just to close this, really inspiring
discussion.
You know, if you think about, you know, a bunchof funnels will be listening to this podcast.
What's the one thing you want to tell them?
About the space and why they should be part ofit and, you know, the future of longevity.
I mean, I guess, again, my hammer is makingcompanies.
(34:51):
So that's pretty much the only thing I considermyself qualified to speak on.
But and you also asked earlier about, like, Sowhat is the process of fundraising like?
Me, it's been the absolute peak experience ofmy career to focus on something that isn't
incredibly exciting and inspiring mission.
It makes hiring easier.
It makes fundraising easier.
(35:13):
It makes motivation for myself for everyonejust automatic.
But I think that for people wondering, whatshould I do with my life?
What should I do with my career?
Whatever that is.
Always been confused by the concept of what acareer is because it's always just me and,
like, what should I do today?
If you realize that you personally really feelthis world view in a deep and vivid way.
(35:33):
Like, yeah, it makes sense that the world willbe a better place if people are not dying of
such horrible age related diseases at the agesthat they're dying of then.
It makes it easier for you to live an authenticand successful life.
Just seek out companies that think and believelike you do and work with the people.
You'll get up every day being excited to beworking on the problem that you're working on.
You'll be working with Pete who get you and whoare also excited about it.
(35:55):
Make team work easier.
It's less sort of every person for themselves,just sort of how I see much of academia and
more of, like, what are we gonna as a team,which is an incredible feeling.
I'm the happiest I've ever been running thiscompany.
And if I'm making decisions, they're not basedon, well, this is what I want you to do for me.
It's like, I think this is the right thing forus to do as a company in order to achieve our
(36:16):
mission.
So I'm out of the way.
Like, my ego is out of the way.
So I guess as I'd advise someone Pete involvedsomething that you deeply believe in and, like,
many other obstacles will just, like, melt awayin your life.
Very cool.
Alex?
I
love that.
So, I mean, for those people who that speaksto, I'll go a little bit more tactical.
I think there's, like, 3 massive, you know, Imean, there's way more than this, but three
(36:37):
core challenges I'd identify that, like, areactually semi feasible on a like 30 to 50 year
time scale and would be the most transformativeto society that we've ever seen in terms of a
company transformed society, which I think islike, 1, is like figuring out how to manipulate
aging for each tissue in the body.
I think there's probably like pretty tissuespecific targets to aging and figuring out ways
(37:00):
to do that, whether that's with reprogrammingmodalities or transcription factor based
screening or, you know, the who knows, like,whatever the intervention is, just figuring out
how to do would be unbelievably remarkable.
2nd one would be to figure out a way to be ableto replace any single damage cell in the body
or age cell in the body with a young fresh oneand get to be where it needs to be and have it
(37:20):
be happy and performing its functions.
And the third would be to be able to do thesame with every tissue in the and I think these
are, like, grand challenges.
They sound insane, but on a 30 to 50 year timescale, who knows?
Like, maybe feasible with the pace that we'reseeing, things accelerate and machine learning.
Like, who knows?
So I would say take Joe's advice.
Go after one of those three buckets.
(37:41):
And you may build the most transformativecompany that's ever graced the earth.
Amazing.
Amazing.
So, again, you heard it first.
You know, aging is a disease.
It's a root cause of most diseases.
We can tackle it.
People are tackling it.
People are investing in it.
So please, you know, if you're excited aboutwhat you heard right now, get up and join a
company, start a company, and do something inthis space.
(38:03):
You know, we can do it.
Thank you very much.
All of you.
Thank you so much for coming.
Thanks, Hillary.
Pleasure speaking
Thanks a ton.
It's all great to be here today, speaking with2 of my favorite people, Alex and Joe, on my
favorite subject, longevity.
At NFX, we call longevity, the transition fromseek care to health care, Morgan instead of the
current state of waiting for somebody to getsick and playing a game of whack a mole with
the different diseases that manifests as we getold, why not tackle the root cause most
(00:27):
diseases, which is AG.
So let's start with a quick introduction.
Joining us today is a Jo from RetroviralSciences, and Alex from the age one fund.
So let's start with Joe.
Can you please introduce yourself and say a bitabout the company's mission?
Yeah.
I'm Joe.
That's the and CEO of retro Biosciences, whichis, sort of medium sized biotech startup in
California.
(00:48):
That's about sixty people now, and we are veryfocused on our mission of adding 10 years of
healthy lifespan to humanity.
Yeah.
I love the mission.
Always when we meet, I ask myself why only 10years?
I think that if we are successful in ourmission that I will be so incredibly proud of
(01:09):
all of us and that the impact on so many facetsof society and people's lives will be so great,
but it feels enough for me as a person.
Impact wise.
Yeah.
And we can always have stretch goals.
Great.
Alex, can you please introduce yourself and theage one fund?
Yeah.
Absolutely.
You so much, Andre, for having me on.
But my name is Alex Coeville.
I'm the general partner and co founder of age1, which is venture firm focused on longevity
(01:34):
biotech specifically.
So specifically focused on catalyzing andfunding very early stage companies that are
working to this goal exactly like Joe's amazinggoal of increasing healthy lifespan.
We don't put a year on it.
We're running we're on it.
Maybe that's less ambitious or more in I don'tknow, but what I do know is that age 1 in
essence came from the longevity fund, which myco founder Laura Deming made back in 2011 as
(01:59):
kind of the first venture capital fund focusedon the theme of longevity.
And we're super, super excited to haveintroduced age one last year and just to have
closed our first fund out of this new vehicle.
So, yeah, congratulations.
I know what drew me to the space, but, Joe,what drew you to longevity space?
I guess I went through a bit of a lifetransition I guess backing up, the only thing I
really know how to do is startups.
(02:21):
That's like the hammer.
And so I go around the world looking for nailsthat I wanna pound in.
And originally, it was doing things that werecool.
That was enough for me.
I think that's maybe it's a young person'sJames.
But then after succeeding reasonably well atsomething, well, I decided I wanted to make
something meaningful.
And meaningful to me means people becausepeople are special compared to, like,
(02:41):
everything else in the universe that we knowof.
And so of the things that are meaningful toPete?
Like, you know, what affects, like, people'slives?
Like, war, famine, poverty, displaced homes,all that kind of stuff.
Pretty much all that requires extreme politicalacumen, which I don't have.
I'm a nerd.
So, like, what can a technologist do of thethings that I could work on technologically by
(03:04):
far in a way the greatest source of humanmisery.
And therefore, the thing that could, if it wereeradicated, could create the greatest source of
human joy and thriving is dealing with disease,which sounds like a huge giant, you know, like
boiling the ocean kind of task, but thenlooking at disease, like just stacking it up,
like, what are people suffering from athospitals?
(03:24):
What is money spent on at hospitals?
It's like 85% age related disease.
It's not like I have to go around and, like,fix kidney disease and fix psoriasis and fix,
like, to fungus or whatever.
Like, all these diseases.
It's like, aging is basically it.
It's basically, you know, pretty much all ofdisease that we ultimately deal with in the
hospitals and so age related disease.
(03:45):
So that, that makes it more focusing for me.
Well, I should figure out why they happen.
What is this process called aging?
And is there some way by addressing thatitself?
It could make the biggest difference
That's great.
And by the way, it's always amazed me how thekind of the backlash we're getting in the
longevity space where some people say, oh, youknow, it's, the tech bros want to live forever,
or other people think, oh, I don't want to beninety year old for 50 more years.
(04:09):
And in my mind, what longevity is is juststaying healthy.
The best health care is to be twenty two yearsold, right, to be young and healthy for meal
longevity is staying young for as long as youwant and involuntary Right?
So that's my mission at least.
So, Alex, you're a scientist, now investor.
What made you Flint realize that this is whatyou want to spend your time on?
Yeah.
For me, it was kind of like the eight year oldmoment of watching people go through the worst
(04:34):
parts of age related disease.
And kind of seeing somebody go throughdementia, seeing somebody else go through
cancer and kind of starting to ask why.
And, you know, you kind of ask why a lot and,like, why there aren't more options to do
something about, like, how horrific both ofthose diseases are and how much suffering comes
with it and, like, it's just that game of whythat you, like, keep asking why, and it it's
(04:56):
just, like, you don't really get the answer toyour question.
And, you know, people Beller you, oh, becausethat's the way it is.
Or, like, oh, that's life, that's aging.
That's just like what we deal with, and peoplekeep asking you why, and you just get more
frustrated.
And eventually, I kind of, like, sat with thatfor probably, like, 5 or 6 years pretty
silently, just like very unhappy about it.
And eventually that led to kind of late teensgoogling more about it.
(05:19):
And during undergrad James across through mygoogling this field of the biology of aging and
longevity biotech that we're here to abouttoday.
And that was when I was like, holy cow, foundmy tribe, these are my people, and haven't
looked back since.
Perfect.
It's a great segue because I really want totalk about the scientific history of longevity.
In my mind, one of the rate limiting steps forlongevity is a lack of scientifically valid
(05:42):
things to do.
Not a lot of things you can do.
And when we found one, there is a lot of energybehind it.
Right?
So it's so important, to discuss what's alreadyhave been discovered.
So, Alex, you've been doing research in thisspace for a while.
Age 1, I think, is the first longevity Pete,right, that's the name of your So can you
please talk a little bit about the kind ofscientific history of longevity?
(06:02):
Yeah.
So the scientific history of longevity is veryinteresting and, you know, it's certainly not
up to me, to determine when exactly the fieldwent from mythology to actual science, but the
answer probably lies you know, I think areasonable answer to it would be maybe sometime
in kind of like the early 1900 with the studyof calorie both done in model organisms and
(06:25):
also in humans.
And this kind of eventually led to the work ofLeonard Heyflick and Lenny Hey life, in
essence, he worked a lot on telomere biologyand kind of showing that cells in a dish do not
divide indefinitely.
There's this in essence, distinct replicativelifespan in a dish, and I think this was very
(06:45):
transformative to people in terms of realizingmaybe the limits of aging or what may be, you
know, a distinct part of the aging process.
And then, you know, pretty much in kind of sameera of a decade or so later, we got to see the
very first quote unquote longevity genes,which, yeah, you're spot on age 1.
It originally came out in a paper from MichaelClass.
(07:08):
I think it was 1983, and it came from anunbiased screen in worms where they, in
essence, gave worms a mutagen that caused abunch of single gene mutations, and they ended
up getting, I think, like, 8 or 10 strains thatwere long lived out of that, and they didn't
realize until kind of subsequent follow-uppapers, but eventually they were able to
characterize that I think all of thosemutations were a part of age one this gene that
(07:32):
was shown to be kind of the first to increaselifespan and increase lifespan in the worms by
about 50%.
And then this eventually led to a secondlongevity gene down to from Cynthia Kenyan's
work at UCSF.
She several times called it the Grim ReaperPete, and this kind of eventually led to more
of this modern field being able to study kindof single gene mutations and look at their
(07:54):
effect on health span and lifespan.
Cool.
I guess the question is what range, right,because, you know, people ask me if somebody
interested in longevity, what should I do?
Right?
You know?
And I think even 5 years ago, what I would tellpeople is, you know, don't die from stupid
things, you know, drive carefully, you know,eat well, sleep well, exercise, but other than
that, there was nothing really to move theneedle.
(08:16):
Has something changed in the last 5 years that,you know, you're excited about?
I'll start with Joe again.
I think as a secular trend, 1, we're justgetting a lot better at biology in the last 5
years, and we're made of biology.
And aging is caused through biologicalmechanisms.
And that just makes it faster to figure outwhat's going on and how it works.
(08:36):
And 5 years has been a really meaningful time.
Like, people started doing single cell.
Like, I think single cell was one of the mostsignificant steps forward in understanding
biology.
Before that, people thought of, you know, therewas this epic moment of sequencing the human
genome that happened in, you know, 2001 ishRight?
But it turns out that all our cells are notexactly identical.
(08:57):
We seem to be composed of all these differentcells that are doing different like skin cells
and brain cells and germ Beller.
And getting to the point where we couldactually look at our tissue as an assembly of
this rich extremely diverse multi interactingassembly of all these different dozens and
hundreds of cell types.
I think that picked off another inflectionpoint.
(09:19):
In bio.
As far as I like just, I have observed it.
And, you know, we started doing single cellsequencing earlier, but it seemed like roughly
within the last 5 years, I think thebioinformatics have started to catch up.
You know, because there's this interplaybetween kind of, like, people making tools and
then people figuring out how to use the toolsand learning a much about the biology or any
science in general.
And then the toolmakers think saying, Hey,there's some new stuff in making new tools.
(09:40):
And, you know, there's these cycles that goback and forth.
And I think in the last 5 years, people reallystarted figuring out how to make a meeting out
of the data that that single cell sequencingtool was generating.
Now we're seeing a rush of new machines beingbuilt.
Then they have to catch up and figure out whatto do with the data and so on.
I think that's been the biggest trend, butthat's just a sort of a general biology trend.
Then I think in terms of the aging field, Oneof the things that happens when you're watching
(10:03):
from afar in any given overall exponentialprocess, like, I think things sort of get or
steam with time First, it's just a few kind offringe researchers, you know, like, throwing
mutagens on worms.
They're interested in aging.
One here or there, people saying what if in avery open minded scientific way.
And then there's another one, and, and someoneelse reads their paper a year later and thinks,
(10:23):
okay.
That was a pretty disciplined scientificallyrigorous way of studying this.
I guess I could do that too.
This isn't all just like, you know, liveforever religion weirdos that don't do real And
I think more people read those papers and morepeople get involved.
And that's an exponential process, you know,more than 2 people read a paper.
And so I think that this field has been takinghold as a rigorous and legitimate scientific
(10:44):
endeavor exponentially.
If you're looking at it from an outside linearpoint of view on an exponential process, tends
to look like nothing's happening.
And then all of a sudden, something'shappening.
You know, there's this elbow in the curve.
And I think that's where we are right now.
We're at the point where this exponentialprocess is starting to make a linear dent in
all of bio academia.
And then usually academia kind of startssomething and says, hey.
(11:06):
This is possible.
But look at these phenomena, and then businesscan then jump in afterward and say, Wow.
Yeah.
It's possible.
Let's make it actualized for Pete.
Yeah.
For me, I have to say my excitement for thespace always started the science behind the
space, always started with just basicunderstanding of the rule of nature, like
nothing in what we are trying to do doesn'tinvalidate the rules of physics.
(11:28):
Like, it seems like we should be able to solvethe problem, and I just gave a token.
Conference.
And I started it by staying 1st Nature solvedaging.
Right?
If you think about an AT or old, we can have ababy with forty year old, then that baby will
have the same lifespan as a baby boy to 2teenagers, right, that you're something magical
about nature.
Otherwise, we won't exist that Joe mightdisagree, but when you zero everything out,
(11:52):
when you start with an embryo, you kinda resetlifespan.
Right?
It's kinda magical Otherwise, we won't exist.
Any species would exist.
And the second thing I'd like to say is humansfor aging.
When you think about aging of our cars or ourbuildings, how we solve the aging for cars, we
just keep replacing parks.
So the basic, I think, can be solved.
Like, there is nothing in what we're trying toachieve that is impossible.
(12:15):
We just need to find some typically valid waysof doing it.
And that takes me to the state of the art.
Right?
You know, Alex, you're investing in the space,So to move things forward, what would you
consider as the most cutting edge topics in thespace right now?
Yeah.
I think probably along those lines, because Imean, in part what's so funny is, like, well, a
lot of the things that we're so excited abouttoday, scientists and folks were very excited
(12:36):
about in the 1990s.
For example, and, like, the whole notion ofreplacement parts or, you know, being able to
target biological pathways that slow or preventthe rate of aging more broadly.
Like, both of these, were, you know, extremelyhot topics of discussion in the nineties.
Amongst among the among the very nichescientists in this community.
And so then it's like, okay.
(12:57):
Well, why the heck are, like, now we're, like,still just as excited about it and yet feel so
much more just defied in our excitement aboutit versus them.
And I think it really is, like, the progress oftools and the basic science behind these
things.
And kind of to segue into your question of,like, you know, a cool example is, you know,
the fact that, you know, back in the nineties,everybody's talking about this ability to have
(13:17):
a replacement part and, you know, you give thisreference to the car and, like, this was
something actually that Len Hayflick talkedabout a decent amount where he was like, oh, we
actually haven't solved aging in car becauseyou can only replace parts for so long before
the car still fails to some point.
I mean, what's so interesting from like thehuman version of that is, you know, we wanted
replacement parts back in the nineties, peopletalked about it, and people talked about it all
(13:40):
throughout the early 2000s in terms of havingthe ability to place a cell in the human body,
and we really weren't able to actually feasiblydo it and show that we could do it in humans
safely and effectively until the past 3 yearsor so.
And this part is really remarkable to me.
And then it's a question of, like, what changedto enable us to get to this place where we
actually have the ability to have like celltherapies that are, you know, derived from off
(14:04):
the shelf that we can, in essence, put inhuman, and they'll long term survive and
engraft and kind of serve a useful purpose.
And in part, it was like Shonya Yamanaka'samazing Nobel Prize winning work around Beller
reprogramming.
In part, it was on the boat of a lot ofscientists who had to optimize the process of
kind of differentiating cell types from IPSCs.
(14:24):
And in part, it was just a lot of people whomade all the other sort subtle optimizations
that needed to happen from a deliveryperspective and otherwise to, like, get the
conditions just right to show that we could doit with just a couple of cell type And, you
know, the evidence and reward of this has beenwe saw just a couple weeks ago, a company in
the Parkinson's disease space that was inessence able to show that they could take these
(14:46):
cells derived off the shelf and Flint them in ahuman Parkinson's brain and and show that they
could survive and and have function for up to18 months in humans.
And so, like, yeah, this is an area I'm justabsolutely incredibly excited about.
That company being Bluerock Therapeutic withseveral others working in that same space and
showing some really cool preliminary evidencein humans.
Like, are we actually at that point that we cannow replace any cell type in the body?
(15:10):
Right?
And then, like, what could get us from now tothat goal?
Or, you know, likewise with human Morgan, alsoinsanely excited about that right now.
As, obviously, you talked about partialreprogramming.
Joe, I think your company is known to beworking in that space.
What drew you to that specific modalities?
I would say a ex sizes, like the things thatpeople talk about in the longevity biotech
(15:30):
space.
You know, there are these molecules that youcould take, for instance, metform.
And, yeah, it seems like it probably slowsaging.
If you give it to mice over long periods oftime.
They'll live, like, 10% longer if you give themmetformin.
But I have this kind of impatient entrepreneurblood in me that I like things that are fast
moving and make big changes.
And the phenotypes that I saw in thereprogramming literature were just huge.
(15:55):
You know, you treat these animals for arelatively short period of time and then the
shifts and the Morgan of aging characteristicsof their tissues of various kinds were quickly
changed.
You know, animals had improved memory outcome.
DNA had less damage, a pretty wide range ofdifferences across tissue and quickly induced.
So I think I would rather work with somethingas an entrepreneur that's kind of like a bit of
(16:18):
a wild bucking bronco and kind of learn to tameit and to coax it into a particular direction
than to take the sort of slow worn out mule andtry you're, like, girded into action.
It's just more exciting for me as anentrepreneur.
So it's a founder.
What do you think your product will be in theend?
Will it be small molecule or antibody orwhatever modality that will slow down aging or
(16:41):
will be something old people take to rejuvenateand to be younger, what do you think your
product will be in the end?
I'm definitely biased toward rejuvenation overslowing aging.
You know, at some point, probably I have toacknowledge a bit of personal bias too.
Because, you know, if I were in my twenties, Iwould probably wanna be at developing things
that I could take over the whole course of mylife and slow me down, but I'm older than that.
But it's not about me I just like to be able toacknowledge my viruses if they do exist.
(17:03):
So we're not a single product company.
We're a single mission company.
I have 5 parallel research teams working ondifferent aspects of aging, different
modalities.
And they have different intervention methods.
So we have a small molecule program.
Our atrophage group.
We have 3 different cell therapy programs.
And then another one that's basically genetherapy program.
So a bunch of different products, and a prettyintensely product oriented.
(17:25):
Like, we are not academia.
We make products for people to take and maketheir lives Beller, but I'm not focused on any
particular modality, like a therapeuticintervention agnostic.
But how do you get it approved?
Suddenly aging is not a disease.
That's what the FDA said.
Need to get approval for a disease.
So how do you get approval for rejuvenation?
Yeah.
Funny.
I was visiting Japan recently, and but theprime minister was interesting.
(17:47):
In Japan, you you can put that someone died ofold age under a certificate.
And I'm kind of interested in the conversationthere that if that's true, then theoretically
you should be able to make a therapeuticprevent that cause of death.
Right?
So I wanna continue that conversation in Japan.
However, right now, I'm in the US, and that isnot a thing.
Aging is not a disease or a cause of death.
(18:08):
So what we have to do is use what I call proxyindications, which means that diseases that are
caused by the same mechanism that we're workingon, but that typically are more acute or
there's a more kind of immediate need,preferably in unmedical needs.
And the ones that, you know, there's anexisting ICD code Morgan that, you know, you
can actually get an approval from FDA to marketa drug for that.
(18:32):
So that's basically every single program has tohave one of those.
And then the idea is that we deliver onmedicine for a proxy indication first, and that
establishes the mechanism is functional andpeople that gets the therapy out there can
establish a safety track record for it.
And then for open minds and doors, to beingable to expand into larger indications.
(18:53):
And then I think this should be the ultimatepath as you alluded to Currier, Umadi, for all
medicine.
Ultimately, it should be able to be usedpreventatively
yeah, the best health care is to stay healthy.
As I like to say, interesting what you saidabout Japan and dying from old age.
I think in the US, they call it naturalreasons, right, know, natural causes.
And I think there is nothing natural of dyingof old age.
You know, natural is dying when you're 22 frominfection.
(19:16):
Know, and and we don't call it natural today.
And I think, in a 100 years, looking back,dying at the age of seventy from old age will
be looked very primitive and very sad thing.
Beller, let's talk about investment and howinvestors Pete the longevity space.
You know, my day job is general, permanent, andeffects.
A big seed fund.
You know, we take money from LPs.
We invest in companies.
(19:37):
We need to show returns.
And the reason we like longevity is, a, wethink it's the biggest market.
It's for everyone, be it's very magical.
Like, if you really invent something thatrejuvenate you and make you younger, like, who
won that.
And it will be totally magical defensible thingto do, and it drives the most passionate people
to the space.
So you get the best founders.
Like Joe.
So maybe Alex, you know, you're a investor likeus.
(19:59):
So what's the framework that you use toevaluate companies in the space?
Yeah.
Well, obviously looking for Joe's, I don'tknow.
Maybe we should need to clone more of him.
That's the easiest solution, but I can do it.
I can do it.
I have a company for that.
In essence, like, you know, I think there'skind of like the 3 things that I'm constantly
thinking about with potential founders, whichis just like, one, do they have extraordinarily
(20:20):
high judgment and like ability to make rightdecisions to our, you know, as at least
somebody on a founding team mission aligned tothe aging fields and the long term goals of the
field.
And 3, are they willing to be a founder?
Kinda like think on those 3 James as of, like,evaluating potential founders or potential
talent that, you know, are the kind of nextgeneration Joe's that kind of help push the
(20:43):
field forward.
And that's kind of like the immediate accessthat I'm evaluating.
I think at least at age 1, we take a super kindof founder focused viewpoint, and that kind of
under that first bucket of like a founder'sjudgment.
So many other of the standard kind of VCevaluations come into the picture, right?
Because, like, how do you evaluate somebody'sjudgment?
Well, I wanna know, like, how they view Pete tomarket, how they view science in a specific
(21:09):
area who they can attract to, you know,associate with from a, like, scientific advisor
perspective.
Kind of, like, what is their ability to, like,run through walls to make that happen?
And so I think, like, all of those kind of foldinto this bucket of, is this agent company
investable on, you know, adventure scale, like,7 to 10 year timeline, right, that kind of fits
(21:29):
in that higher order framework, which I thinkit really comes down to, like, just a founder's
judgment.
Cool.
So you talked a lot about fathers.
Obviously, funnels are very important, butlet's talk about a little bit about the risks
of longevity companies.
One of them is something that Joe justmentioned.
Right?
The FDA still don't recognize aging as adisease.
You need to find an adjacent indication.
(21:49):
I call it take longevity indications because,you know, some people go after osteo for ease
of the knee, and they don't develop a drug fortougher raises.
You develop a drug for aging that might alsohelp with the stopper raises, but might not be,
you know, the best efficacy for that.
Right?
So it's harder to get approval.
What other risks do you see for companies thisspace?
I think losing your way.
Losing your way is a risk.
(22:10):
I think it happens to people in any kind ofmission focused situation.
This isn't really the full mission, but it'spractical for us to work on in the short term.
And then they focus on that forever, and theynever kinda make it I guess that's more of,
like, getting back to, like, personal founderrisk.
But it's something that I constantly repeatback, like, if we're in strategy sessions,
which we do twice a and I'll constantly bebringing back up.
(22:32):
Yes.
We could go that direction, but I think itwould take us off track, and we need to keep
moving our focus back.
Even if it means we face more risk of certainkinds are less immediate reward, it's worth it.
And we're in a privileged position of havingpatient capital, like just our investor, I
guess, the equivalent of your LPs have areasonably long term view.
I mean, also, personally, from a founderperspective, impatient, and obsessed with PACE
(22:56):
as MI.
A really hard problem.
And I think one needs to think on longer timescales to get there.
Like, I don't necessarily think that we'regonna hit our entire mission within 7 year
venture time frame.
I believe we'll make a dent.
For sure.
We'll, for sure, ship our first drug and thenour next one.
And then our next one.
And then I got next eventually, we'll hit ourmission.
I guess there's business risks.
Like, one thing I see happening over and overagain in the biotech industry, and it makes me
(23:20):
sad is that you see a lot of companies startoff with toward a mission, with a particular
discovery platform and really believing in thescience and the power of the science and in the
depths of their pipelines.
We have this platform.
It's a novel way of discovering therapeuticsagainst particular, you know, set of diseases
or whatever.
And then gonna be able to generate, like,dozens of cures for all these things.
(23:43):
And they get one thing that's kinda startedheading for the clinic.
They derisk certain aspects of it, and theystart running out of money.
And then they go talk to investors, and theinvestors like, I don't know about all this,
like, kind of, like, nerdy stuff.
The, like, the sciency discovery stuff with allthose Pete, like, I can't quite figure.
I don't really understand it that well, butthis drug that looks like it's about to go into
(24:04):
phase 1, that makes sense.
I see the business sense of that.
So I'll invest into that, but you have to layoff your discovery team.
So you see these companies constantly start offmore optimistic and idealistic.
And, like, I guess I have a bias toward deeptech, I guess you would call it.
I mean, that's the buzzword in the investmentcommunity.
But I believe that the important changes thathave happened throughout human history credible
(24:28):
lifestyle today have been from not so muchfrom, you know, just like figuring out that we
should have curbs be 6 inches high on thestreet instead of 8 inches high or whatever,
but have been more like putting in theirresearch and figuring out how to make a really
good rocket engine or how to advertise cloneDNA, etcetera.
And so it said to me to see these organizationsgetting deep tacked over and over again.
(24:50):
That's kind of a business risk in a way it'sinspiring to me when I see a company starting
to do well in the investors.
And I guess they've done a good job atcommunicating with their investors and helping
share the vision not only of this first item,but their whole pipeline and the thesis behind
it, and they can keep R and D funded.
Yeah.
The only thing that matters, if you look backin history, the only thing that matters is is
(25:11):
science and technology.
Everything else is just games.
That's the only thing that moves productivityand the human condition forward.
I think we all agree on that.
And let's talk a little bit about thefundraising side because all of us had to
fundraise for longevity.
So, Alex, you had to fundraise from LPs toraise your fund and Joe, you had to fundraise
from other funds or angels to raise money forlongevity.
(25:31):
So, Alex, let's start with you.
You'd think that every person with money, ifyou scratch him, you know, he's a longevity
buff.
He wants to be healthy and live longer.
Was it easy, or was it hard?
How was your experience?
Raising money for all this fun.
Yeah.
I mean, I think I don't know if there is evereasy fundraising unless you're maybe, like, a
machine learning company or something atSilicon Valley these days.
(25:53):
I think almost any fundraising is hard even in,like, the easiest of circumstances.
So I'd say it was, like, way easier than Iexpected, but I also expected to be swallowing
glass for a year.
And I would say it was like a slightly morepleasant experience than that, but it was
definitely a year grind of just making ithappen even though it was a pleasant
(26:16):
experience.
So in essence, what was the experience?
Like, yeah, I mean, I think I found out, forexample, that, like, through some global
travels, people now just when you mentionedlongevity anywhere kind of outside the they
just think of Brian Johnson, and they ask youif that's what you mean by the longevity field.
So I've learned kind of how global the field isgone and turn of getting name recognition in in
(26:36):
terms of exactly kind of how that process goesand kind of people's comfort with the field.
I mean, I think people do start to see it asone of these opportunities that they need to
track.
And even a lot of the more standard, Beller,traditional funds It's on their radar now.
Maybe not as something that they're activelyinvestigating, but it's at least on their
radar, which I think is a crazy difference.
You know, I think back just 10 years ago, 11years ago to Laura launching the first fund out
(27:01):
of the longevity fund vehicle and, like, howhard that must have been to a approach people
for an industry that didn't even exist Pete.
And now we get to sit here with a luxury ofsaying, you know, there's, you know, what,
like, over 180 different companies in thisspace, and people have heard about it for
better or worse, sometimes in either direction.
So I think that's a really cool change that'shappened in the fundraising landscape is just
it's more on people's radars than it's everbeen before.
(27:24):
Yeah.
I think we all agree that longevity might notbe the best names.
I think there's a big vandaigram of peoplethinking about longevity.
What does this mean?
Some people think it's screams.
Some people think it's extreme biohacking likeBrian Johnson.
I think we're in the camp of, like, the deepscience, you know, rational thing that can move
the needle and, you know, prevent diseases.
I think that's the camp that we're if I cangeneralize, that we're all in.
(27:46):
But I want to talk bigger about the businesscase for longevity.
Right, because, you know, not only it's thebiggest market in the world, I'm about to write
a blog post about the business of longevity.
I wanna call it longevity, the l in LTV.
So LTV means lifetime value.
Right?
So in my hypothesis that not only everybodywould to have the longevity drug, but it makes
all other markets better because it increasesthe lifetime of your customers.
(28:10):
They just live longer to consume whateverproduct or service you grading.
Somebody made a business case for, you know,the economic value of adding 1 healthy year for
adults in the US.
It was suffering in the trillions of Beller.
So, again, it's so surprising why there are nomore investment in longevity than they are.
So, you know, Alex, like, why do you thinklongevity companies are great businesses to
(28:32):
invest in?
Yeah.
Like, in part, like, some of the biggestreturns and, you know, examples or areas of the
best financial returns ever seen are kind of inareas where historically the opportunity has
just been completely overlooked and you havemassive, massive markets at play.
And I think that sums up the longevity space toa tee.
We wrote a blog post about it probably like 3or 4 months ago just in terms of the, like,
(28:58):
possible market that's achievable with the 1stFDA approved longevity drug.
And, you know, we included, it would be about a150 to $200,000,000,000 per year in annual
revenue.
So this would be in essence 3 to 4 times thesize of the entire market of GLP 1 receptor
agonists, your Ozempic Wagovi, that Munjarothat has been, you know, totally transforming
(29:20):
economies of European Countries.
Like, if you look at the growth of NovoNordisk, just becoming like the most valuable
company in Europe, I'm pretty sure.
Right?
It's like and that's you know, a third or a 4thof the size and magnitude of the effect that
the longevity field is going to see anexperience.
And we just know that that's gonna be the Themarket poll is there, it will happen is just a
(29:40):
matter of when.
So I think you're spot on.
I'm super excited to read your post becauseit's the massive market that's involved in the
very few shot that have been actually taken toachieve that market.
It's a huge mismatch in terms of shots on Peteand the rewards for scoring.
One of the challenges space has is the proud tobe in a space that has this category.
This this is is characteristic, but there is alot of sort of external value created And what
(30:06):
I mean by internal and external is there's asystem in which the investment is made and the
product is produced and revenue directlygenerated from the product And then there are
the other effects on the rest of the world.
You can make, like, high speed race car orwhatever, and you can get paid x number of
dollars every time someone buys 1.
I don't know about the externalities for that.
You know, maybe it's just, like, incrediblyinefficient and cost lots of pollution and
(30:29):
noise and, like, people die often from themand, like, whatever.
It's like, maybe they make the world a littlebit worse place.
But, you know, you can categorize products thatway.
I think there have been really good Bellerreasoned and detailed carefully calculated
cases made for longevity therapeutics thatproduce them, and pretty much everything gets
better society wise.
(30:49):
The amount of time that you have to supportPete, there's, like, the younger population
support the older population that there's thissort of like ratio that has to do, you know,
it's like terrible in Japan and Korea rightnow.
You know, the retirement versus non retirement,how long can people work basically versus
that's a huge, huge effect.
People are healthier or longer and can remainproductive rather than being a burden to
society.
(31:10):
You don't necessarily get paid for that bymaking your longevity drug, not necessarily,
just effect on families, on a society, onproductivity, on forward progress.
And there are a bunch of things like that thatall ripple out from making good, healthy
longevity drugs that you don't necessarily getpaid for directly.
But I think there are enough still that and bemoney that flows back into the same industry
that produces them, which is a virtuous cyclewhere they can produce more such drugs using
(31:34):
that money, because it takes money to fuel Rand D, that there are enough that will still
incentivize people to continue.
This exponential growth?
Yeah.
Totally agree.
And, Alex, by the way, I think it's kinda funnythat you mentioned GLP drugs, like Ozempic,
etcetera, because when I look back at thebiggest pharma Pete in the last 5 years, which
is GLP drugs and even the COVID vaccines, in mymind, those 2 things are longevity drugs.
(31:58):
It's things that you give to healthy Pete, sothey won't become disease, right, you know,
overweight take that drug.
So you won't get NASH.
So you won't get diabetes.
Right?
So you you won't get heart attacks.
So we see the value of those drugs, and thoseare the biggest drugs categories ever.
It's something you give to everybody to keepthem healthy.
So, yeah, I think the business case has alreadybeen made by other drugs, but now let's attack
(32:21):
the root cause let's talk about the future andkinda advice for founders.
Let's start with, what do you think the longterm society effect will be if this space will
be developed as we think it will?
How the world would look different if we havethose drugs?
I mean, the easiest way to think about that forme is, well, how does the world look different
today from how it looked?
(32:41):
100 years ago when people lived shorterlifespans.
You know, it was life was, you know, nastier,shorter, and more brutish.
I think people will look back on now from thefuture and just be like, ugh, man, that sucked.
I'm sorry that people had to live back then.
I get it.
You know, I read the 20 century literature, andit's pretty brutal life.
And you don't know, you know, people are, like,dying of Alzheimer's and all these other, like,
(33:06):
fundamentally treatable things because theyjust I guess they just didn't have the medicine
then.
Yeah, so it'll be a little bit of sort ofgritty reality and a bit of Pete, probably
Yeah.
Definitely.
So we talk about vaccine.
You know?
So, again, you take something and you never getviral infection if we get better vaccine.
You know, you take GLP 1 inhibitors and you'realways fit and, sexy.
(33:27):
Right?
You know, you take partially programming creamsand you're skin looks young and you grow the
hair back, that's something that I feelpersonally about.
Yeah.
Like, some people hate their birthdays.
I always celebrate my birthday.
James a milestone, I survived another year inmy goal of living in the future because the
future is going to be awesome if, the companywe invested and the company you are working on,
(33:49):
Joe, will work out, right, because we'll havethe solution for all of that.
And I think some people are worried about, oh,it's going to go to reach Pete.
To that, I say an expensive solution is betterthan no solution, and expensive solution tend
to get cheaper over time.
You know, patent runs out and everythingbecomes cheaper and more accessible to
everybody Beller, and I'm excited about thefuture.
(34:09):
I want to live in that future.
Even if it's cost a lot, one of the sciencefiction books I read, the way they fund the
longevity treats is people saved instead ofsaving for retirement, they saved for the
longevity treatment that took them back toeighteen years old and they call it 2nd life
and 3rd life and one saying in the book is,life sucks, then you rejuvenate and do it all
over again, which is way better than our optionright now.
(34:31):
So, again, for both of you, I guess, samequestion just to close this, really inspiring
discussion.
You know, if you think about, you know, a bunchof funnels will be listening to this podcast.
What's the one thing you want to tell them?
About the space and why they should be part ofit and, you know, the future of longevity.
I mean, I guess, again, my hammer is makingcompanies.
(34:51):
So that's pretty much the only thing I considermyself qualified to speak on.
But and you also asked earlier about, like, Sowhat is the process of fundraising like?
Me, it's been the absolute peak experience ofmy career to focus on something that isn't
incredibly exciting and inspiring mission.
It makes hiring easier.
It makes fundraising easier.
(35:13):
It makes motivation for myself for everyonejust automatic.
But I think that for people wondering, whatshould I do with my life?
What should I do with my career?
Whatever that is.
Always been confused by the concept of what acareer is because it's always just me and,
like, what should I do today?
If you realize that you personally really feelthis world view in a deep and vivid way.
(35:33):
Like, yeah, it makes sense that the world willbe a better place if people are not dying of
such horrible age related diseases at the agesthat they're dying of then.
It makes it easier for you to live an authenticand successful life.
Just seek out companies that think and believelike you do and work with the people.
You'll get up every day being excited to beworking on the problem that you're working on.
You'll be working with Pete who get you and whoare also excited about it.
(35:55):
Make team work easier.
It's less sort of every person for themselves,just sort of how I see much of academia and
more of, like, what are we gonna as a team,which is an incredible feeling.
I'm the happiest I've ever been running thiscompany.
And if I'm making decisions, they're not basedon, well, this is what I want you to do for me.
It's like, I think this is the right thing forus to do as a company in order to achieve our
(36:16):
mission.
So I'm out of the way.
Like, my ego is out of the way.
So I guess as I'd advise someone Pete involvedsomething that you deeply believe in and, like,
many other obstacles will just, like, melt awayin your life.
Very cool.
Alex?
I
love that.
So, I mean, for those people who that speaksto, I'll go a little bit more tactical.
I think there's, like, 3 massive, you know, Imean, there's way more than this, but three
(36:37):
core challenges I'd identify that, like, areactually semi feasible on a like 30 to 50 year
time scale and would be the most transformativeto society that we've ever seen in terms of a
company transformed society, which I think islike, 1, is like figuring out how to manipulate
aging for each tissue in the body.
I think there's probably like pretty tissuespecific targets to aging and figuring out ways
(37:00):
to do that, whether that's with reprogrammingmodalities or transcription factor based
screening or, you know, the who knows, like,whatever the intervention is, just figuring out
how to do would be unbelievably remarkable.
2nd one would be to figure out a way to be ableto replace any single damage cell in the body
or age cell in the body with a young fresh oneand get to be where it needs to be and have it
(37:20):
be happy and performing its functions.
And the third would be to be able to do thesame with every tissue in the and I think these
are, like, grand challenges.
They sound insane, but on a 30 to 50 year timescale, who knows?
Like, maybe feasible with the pace that we'reseeing, things accelerate and machine learning.
Like, who knows?
So I would say take Joe's advice.
Go after one of those three buckets.
(37:41):
And you may build the most transformativecompany that's ever graced the earth.
Amazing.
Amazing.
So, again, you heard it first.
You know, aging is a disease.
It's a root cause of most diseases.
We can tackle it.
People are tackling it.
People are investing in it.
So please, you know, if you're excited aboutwhat you heard right now, get up and join a
company, start a company, and do something inthis space.
(38:03):
You know, we can do it.
Thank you very much.
All of you.
Thank you so much for coming.
Thanks, Hillary.
Pleasure speaking
Thanks a ton.
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If you've ever wanted to know about champagne, satanism, the Stonewall Uprising, chaos theory, LSD, El Nino, true crime and Rosa Parks, then look no further. Josh and Chuck have you covered.
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Crime Junkie
Does hearing about a true crime case always leave you scouring the internet for the truth behind the story? Dive into your next mystery with Crime Junkie. Every Monday, join your host Ashley Flowers as she unravels all the details of infamous and underreported true crime cases with her best friend Brit Prawat. From cold cases to missing persons and heroes in our community who seek justice, Crime Junkie is your destination for theories and stories you won’t hear anywhere else. Whether you're a seasoned true crime enthusiast or new to the genre, you'll find yourself on the edge of your seat awaiting a new episode every Monday. If you can never get enough true crime... Congratulations, you’ve found your people. Follow to join a community of Crime Junkies! Crime Junkie is presented by audiochuck Media Company.