March 24, 2025 • 46 mins
You're defined in part by the genome you arrive with -- so what does it mean when you can edit it? What does this have to do with viruses, copy-pasting, and whether we will modify the story of our own species? Join Eagleman with guest Trevor Martin, CEO of Mammoth Biosciences, for this week's episode about the remarkable situation we find ourselves in, now that we know how to read and write our biological inheritance.
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Episode Transcript
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Speaker 1 (00:05):
We are defined in large part by the genomes that
we happen to come to the table with. So what
does it mean when we can edit our own genomes?
What does this have to do with viruses or copy pasting,
or whether we are going to modify the story of
our own species. This is in our cosmos, and I'm
(00:29):
David Eagleman. I'm a neuroscientist and author at Stanford And
in these episodes we sail deeply into our three pound
universe to uncover some of the most surprising aspects of
our lives. Today's episode is about the remarkable situation we
(00:54):
find ourselves in, which is that we now know how
to read our biological inheritance. Now, this is very easy
to take for granted because for most of us this
has been true for our whole lives. But it's a
very recent ability for our species. It only began in
the second half of last century. In my postdoctoral fellowship,
(01:17):
I worked with Francis Crick, who was the co discoverer
of the structure of DNA. In April of nineteen fifty three,
he and James Watson published a paper in Nature, and
in just over a page they proposed the double helix
structure of DNA, explaining how genetic information is stored and copied. Now,
(01:41):
there's something about this paper that always makes me tear
up when I read it, because the insight changed our
world and almost certainly the future of our species. What
they realize is that DNA is made of two complimentary
strands wound around each other, and the bases are which
just means A on one strand always links with T
(02:03):
on the other, and C with G. And this gives
a mechanism for making a xerox copy of the whole thing,
because you just unwind the two strands and then each
serves as the template for sticking on new bases in
the right spots. But what I want to emphasize is
how new this is. Nineteen fifty three, isn't that long ago?
(02:24):
World War Two was over, Eisenhower was president of the US,
and by this point we already had automatic transmission in
cars and color television and microwave ovens. But we had
no idea why your ears look like your father's ears,
or your eyes look like your mother's eyes. Just imagine this,
(02:46):
before the discovery of the DNA code, how difficult it
was to understand how inheritance actually happens biologically. People floated
all kinds of wacky hyppods disease about it, like maybe
each sperm cell contained a super tiny embryo. But everyone
(03:07):
knew these models didn't work. And even while people were
driving cars and watching TV and microwaving, they knew that
inheritance was a total unknown in science. And then that
all changed with that very short paper that laid the
foundation for modern genetics and molecular biology and ultimately technologies
(03:31):
like gene editing, and so that puts us where we
are now. For as long as animals have walked this earth,
we have been shaped by forces beyond our control, by
the slow hand of evolution, by the accidents of mutation,
by the blind winnowing of natural selection. The twisting helix
(03:53):
of our DNA has been sculpted by nature's chisel. But now,
for the first time, we are holding the chisel in
our own hands. Just in the last nanosecond of evolutionary time,
we now command gene editing technologies, things like crisper and
(04:15):
single base pair editing tools and epigenetic editing tools and
tools yet to be imagined, and these give us the
power to rewrite the code of life itself. We can
correct genetic disorders, we can eliminate inherited diseases, and we
can presumably even enhance ourselves, pushing beyond the biological boundaries
(04:41):
that we would have recently assumed are fixed. The rules
of genetic inheritance were once immutable, but now they are revisable.
So obviously, with this power comes deep questions. If we
can edit our genetic destiny, what should we choose to become?
(05:03):
Do we cure only what ails us? Or do we
optimize ourselves enhancing features like intelligence and strength and longevity.
How close are we to doing any of this? Does
anything happen to the meaning of human struggle? When suffering
can be edited away? Will we remain the same species
once we begin sculpting ourselves? And who decides is it
(05:28):
the scientists at the lab bench, the policymakers and government,
the parent holding their newborn in their arms. What are
the ethical and social and existential questions of putting our
genetic future in human hands? So in today's episode, we're
(05:48):
going to step into the frontier of gene editing. What
does it mean to be human when we are no
longer bound by the limits of our biology. What stories
will future generation tell about the choices that we make?
Now the code of life is no longer written in stone,
so what will we write? So I called my friend
(06:10):
Trevor Martin, who is the co founder and CEO of
Mammoth Biosciences, which is based here in the San Francisco
Bay area. They are building the next generation of Crisper
products for editing the genome. If you've never heard of
Crisper or aren't sure what it is, hangtight because we'll
get to that in a minute. But the quick preview is,
how do you build a platform to read and write
(06:34):
the code of life? How do you make tools? So
you get something like a word processor for the genome
where you say, look, I just want to hit control
X to cut a piece of the genome, or control
V to paste it, and control F to find some
sequence inside the genome. So here's my conversation with Trevor Martin.
(07:00):
Technology is some of the most amazing technology we have,
but it wasn't actually invented by humans. It was merely
discovered by us. So tell us about that, tell us
about Crisper.
Speaker 2 (07:08):
Yeah, So, similar to how we have immune systems, actually
bacteria and small microbes and just teny little organisms. They
have to defend themselves against invasion as well. Typically viruses
actually much like us, and one of the ways that
they evolve to do this is this thing called crisper
that has become famous, of course for its ability to
(07:30):
do genetic editing. But fundamentally nature has used these crisper
type systems to protect themselves from viruses, very similar to
how our adaptive immune system protects us from viruses.
Speaker 1 (07:42):
And we've kind of ripped that out.
Speaker 2 (07:44):
Of nature and done a ton of engineering on top
of it to turn it into these technologies that can
do genomic engineering. But that's kind of fundamentally where it
came from. And I think it's this beautiful example of
leveraging billions of years of evolution and combining that with
human ingenuity and a lot of hard work from a
lot of scientists.
Speaker 1 (08:04):
So let me get straight. So, so crisper if fits in,
Let's say a single cell organism, a virus injects some
DNA and it's got to figure out, hey, that's not mine,
and then it cuts it up exactly.
Speaker 2 (08:14):
So there's a bunch of complicated steps there. First, it
has to recognize Hey, that's not mine. Then it has
to cut it up. And then actually there's a third step,
which is, hey, I should remember this came and i'd
want to make sure I protect against it in the future.
And it's actually funny, that's where the name crisper itself
comes from, is that I want to protect against the future.
So CRISPER is actually an acronym stands for clustered regulatory
(08:35):
interspace short palindromic repeats and this is actually kind of
the memory of the cell that the crisper systems used
to say, Hey, these are viruses that have invaded me before,
and I want to make sure they don't do it again.
Speaker 1 (08:48):
And this happens in unicellular organisms. That's so incredible, Okay,
And so you started this company Mammoth with the idea
to take these crisper systems and I prove them from
what nature has done or search for other ways of
doing it. So give me a sense of how you
do that. Yeah.
Speaker 2 (09:06):
So probably the most famous Chrisper system is this thing
called CAST nine. And this was what one of my
co founders, Jennifer Dalna, won the Nobel Prize for a
few years ago. Was the work in terms of really
characterizing and developing this into a geneomic engineering technology. And
CAST nine was just one example from a certain class
of bacteria of this type of crisper technology. And one
(09:30):
of the fundamental insights of Mammoth is that actually, there
are all sorts of Christopher technologies out there, because these
are present and all sorts of microorganisms, bacteria, even large
viruses archaea. And our insight was, hey, we should look
through all of these alternative versions of crisper that are
not CAST nine and do a lot of work to
(09:50):
develop those, and that could actually have a huge benefit
for building genomic medicines, for building diagnostics, for improving agriculture.
And that was kind of a fundamental insight that was
maybe obvious today, but at the time people were so
focused on CAST nine that people weren't really looking beyond that.
Speaker 1 (10:06):
So you're looking for things that have already been discovered
by nature elsewhere, and you're looking for versions of that
that do what you want in terms of gene editing.
Speaker 2 (10:17):
So the trick there is that you use nature as
a starting point. And the unfortunate truth is that when
you take these things and you rip them out of nature,
actually usually they don't work at all, but they give
you a starting point. And one of the fundamental insights
we had was it's not enough just to go into
nature and to say, ah, okay, what other alternative crispers
are there? You have to do that, and then you
have to do a ton of engineering. And we actually
(10:39):
have a whole floor of our building that has these
liquid handling robots. They're just running tens of thousands of
experiments at a time and you just kind of grind
away and you can use the latest AI techniques combining
it with the latest and microfluid candling is what those
robots are called. And it's only with that combination of
all of that, with this kind of usually very wacky,
kind of natural starting point. That's the secret sauce one
(11:00):
or the other is not enough. You have to really
have both together. And that was the unique insight as well.
Speaker 1 (11:04):
Oh great, okay, And so they're looking for these smaller systems,
and what's the reason to have them smaller?
Speaker 2 (11:11):
Yeah, So one of the giant challenges of the field
is how do you deliver these systems to the cells
that need it the most. So when you and I
think about genetic medicine, what comes to mind, it's going
to be things like Alzheimer's, Parkinson's, Huntington's, you know, these
really debilitating disorders where they can be basically a death
sentence and you something that's kind of known in your
genome from birth. And the big problem though, has been
(11:35):
what the genetic medicine, the crisper field has been focused
on is a tiny subset of diseases that are typically
not that and that's amazing for those patients that have
diseases that are like blood disorders or like certain liver disorders,
and there's amazing progress in this field, like for example,
there's now an approved therapy using Crisper for sickle cell
disease in beta talasmia. Those are overlook diseases with underrepresented
(11:56):
populations and that's a huge win for the field. But
the proms of genetic medicine is not just blood disorders
and liver disorders. The promise is to go to any
cell in the body and do any kind of edit.
And that really is what guides us at Maamath that
means you need to go to the muscle, you need
to go to the brain, you need to get to
the heart. And that has been a gigantic challenge, and
it's because CAST nine is actually a big protein. So
(12:19):
obviously it's small relative to us, like all proteins, but
it's really really big on a kind of molecular scale.
And one of the things that we did is we said, hey,
could we create a crisper system that's not just a
little bit smaller than CAST nine, but it's way smaller.
And that resulted in a thing we called nanocasts nano
and that was really exciting and there's a lot of
(12:40):
skepticism in the field, which is great for our patents,
people like, oh, these will never work. And it required
a ton of work and a lot of these robots
doing a lot of work overtime with our scientists. And
what's cool though, is that now we actually have data
showing that in monkeys, which is a really high bar.
It's not you know, cell lines or mice, we actually
get extremely good editing either equivalent or better than CAST
(13:04):
nine with these really really tiny systems. And these really
tiny systems, unlike CAST nine, can actually be delivered anywhere
in the body, so that's a seed change in terms
of what's possible.
Speaker 1 (13:14):
And they can be delivered by a virus for example.
Speaker 2 (13:17):
Yeah, So a classic way that you can deliver to
muscle or brain, for example, would be with a thing
called AV which is another acronym that stands for adno
associated virus. And one of the big limitations of this
is that it has a very strict size limit. Like
you can think of it as like a semi trailer
truck where you can only fit so much in the
back and cast nine is just way too big to
(13:38):
fit inside it. But these nanocast style systems don't just fit,
but they actually have a ton of room to spare.
And the room to spare is really important as well,
because when you're a scientist you can start to think
really creatively about how do I use that. And one
of the key ways that we use that is to
fit in the machinery to do different types of edits.
So people may have heard of things like base editing
(13:59):
or writing or epigenetic editing. These are all techniques that
take the fundamental Chrisper system and say, hey, what if
instead of editing the genome as this like word document
and only being able to delete sentences, what if we
could add a paragraph, What if we could spell check
a word? What if we could italicize a sentence. These
are all kind of different types of edits you can
(14:21):
do in the genome, and they require delivery have even
more machinery, and that means that Mammoth has really been
the only company that's been able to actually deliver not
just anywhere in the body, but also deliver any kind
of edit anywhere in the body. And I think it's
you have to do both of those if you really
want to address all genetic.
Speaker 1 (14:37):
Disease, and any kind of edit means reading or writing. Yeah.
Speaker 2 (14:42):
So we also had a lot of work we did
on diagnostics as well, and during the pandemic we actually
got emergency use authorization for a Chrisper based COVID test.
So we're super proud of the work we did there.
The focus of the company today is very much on
the writing side, but definitely I think there's huge potential
on the reading side.
Speaker 1 (15:00):
As well. Give us an example of the reading side.
Speaker 2 (15:04):
Yeah, so basically there, instead of using the Chrisper systems
to change the DNA, you can use the Chrispher systems
to send out some signal that there's a certain sequence present,
so to say, hey, I found the word potato and
it'll glow green if it finds potato, and it won't
show any color if it doesn't. And that's a very
(15:24):
powerful kind of concept, and that means you could do
really low cost, high accuracy style molecular testing, and that's
something that we're very bullish on long term. But as
a company, obviously you have to focus on a certain area,
and already, you know, trying to tackle all genetic diseases
a limited set of focus to begin with, So that's
(15:45):
kind of kind of where we're focusing our efforts otherwise.
Speaker 1 (15:48):
Right, So let me come back to something you said. So,
as far as the writing goes, you can write single
base pairs, you can write something longer. You can write
whole genes or collections of genes. Ice.
Speaker 2 (16:00):
Yeah, you could have all insert an entire gene. You
could kind of change a single base pair out of
all the billions of base pairs in your genome. And
that's an important philosophical point as well, because I think
in biotech we often get so enamored with technology, so
we always think in terms of like, ah, this is
a base editing technology, or this is a gene writing technology,
This is like Deuvile's trand break if you're patient. You
(16:22):
don't care, Right, I have a disease and I don't
care how you're doing it. I just want you to
cure or treat my disease. In our case, we can
actually cure it. And I think that's where our philosophy is.
Will actually develop many techniques, all the techniques, and actually
be able to deliver them. And then for any disease,
we might try a couple of different ways of doing it.
(16:42):
We might say, ah, there's like a way to do
it by base editing, there's a way to do it
by epigenetic editing. We're not sure which one's gonna be
the best, but we'll try both and see which one
actually works well. And that's very different from philosophy from
typical biotech, where you try and create like ten companies
whe each company is doing a different method and I
think that's all fine and well in some ways, maybe
also from like how do you maximize like investor involvement
(17:06):
in different companies, But from a I think long term
company building and from a patient perspective, I think that's
very much like the wrong way to go about it.
Speaker 1 (17:14):
Yeah, So tell us about diseases in the brain and
what you're thinking of, is the future of those maybe
in give me a sense of three years, ten years
where we'll be with that. Yeah.
Speaker 2 (17:25):
So to start with a specific example of one that
I think kind of is frankly a condemnation of the
genetic medicine space is Huntington's disease. So this is a
disease that was mapped, Oh my god, not just decades ago,
like half a century ago, like I think in like
the late eighties, and it was mapp They mapped it
with microsatellites, I believe, on giant gels that were in
(17:46):
the lab. Right, this is like, you know, not pre computer,
it's like Wexler, right, Yeah, but you know, very very
early technologies, and we have understood, you know, fundamentally kind
of the genetic base of Huntington's for a very long time,
and still today people die from this every single year,
and it's a horrible disease where basically, if you have
a certain genomic sequence, then you know, typically in your thirties,
(18:10):
you'll have the accumulation of a certain protein and you'll
pass away. And it's infuriating, honestly that we understand the
genetic cause of this and we can do nothing about it.
So I think the genetic medicine space and Crisper in
particular will have arrived and will have really I think,
done a hallmark deliverance of like what the true potential
(18:33):
is the day the last Huntington patient dies?
Speaker 1 (18:35):
Agreed? When is that? Do you think?
Speaker 2 (18:37):
Yeah? So, I think it's definitely within sight. I'm not
going to give a specific.
Speaker 1 (18:42):
Three years or five or ten.
Speaker 2 (18:44):
Yeah, it's probably not three, but it better not be ten. Okay, Yeah,
I think in general, like you can kind of see
the steps that you need to take and it's a
matter of walking down the path.
Speaker 1 (18:55):
Got it? And what has been the problem? Given that
we have Chrisper cast technology and that we have known
the gene for Huntington's it's monogenetic, what has been the
hold up? Yeah?
Speaker 2 (19:05):
So I think there's a lot of things you have
to think about. One is what type of edit are
you going to do? Like can you just knock out
the whole Huntington gene or do you have to think
more creatively about modifying it in a more subtle way.
Then the second one is can you actually get the
editing machinery to the cells of interest? Can you actually
get this into the brain, and those are two of
(19:27):
the most obvious problems. I think that we've really thought
deeply about mammoth and like the general sense, not just
running to the before any brain disease. And I think
that's where the technologies we've developed, like these ultracompact systems
and having all these different editing modalities I think can
make a huge difference.
Speaker 1 (19:43):
Potentially got it and so it sounds like you've got
the can we get it to the right cells? It
sounds like you've got a beat on that. But as
far as what edit to make is that something you're
experimenting with, well, I.
Speaker 2 (19:55):
Think that's definitely something where we have a lot of
great ideas for any about like different types, and that's
where we're very unique because we can actually try different
methods and we can say, hey, this is our hypothesis,
prove it out or not, but not have a hammer
and everything else to look like a nail, which is
very very classic not just a biotype but a deep
tech in general. And you know the classic startup advice
(20:17):
of like find the problem first and then figure out
the solution. There's a lot of reasons why that doesn't
work in deep tech right, Like, sometimes you really do
have to kind of build the thing and then figure
out what the best application is. But that being said,
the more you can mitigate that, that's a very powerful
idea to get away from hammer, you know, squint at
everything until it's a nail.
Speaker 1 (20:36):
Yeah, let me make sure I understand. What's the way
that you can test out these different hypothesies. Do you
(20:57):
have an animal model of Huntington's.
Speaker 2 (20:58):
Yeah, it's gonna so not speaking specifically about Huntington's, but
just generally in terms of different diseases. Some diseases you'll
have an animal model that's really good, and that means
you can actually try it out like in mice or
maybe even monkeys, and like really get a lot of
confidence for others. Honestly, you don't have anything. Maybe there's
no animal models, so like you have to try it
out in cell lines and then kind of make your
(21:19):
best guess about what's going to work.
Speaker 1 (21:20):
Well.
Speaker 2 (21:21):
So it's very varied, i'd say, across different diseases and
across different tissues, but you want to have as many
shots on goal I think as possible because then when
you go to humans, maybe you'll find something surprising, Like
you only had cell line work and then it doesn't
work in humans. And if you only have one technique,
you're kind of out of luck. But if you have,
like you know, a backup or a backup to the backup,
(21:43):
that means you can actually go in and you know,
do something for patients after that.
Speaker 1 (21:47):
Got it. So that gives us a good sense of
what the challenge is with something like Huntington's. Now, Huntington's
is one gene. If you got it, you're getting Huntington's.
But what about other diseases, whether it's Alzheimer's or schizophreny
or whatever, that are polygenic, I can involve lots of machines.
Does that make the problem exponentially harder.
Speaker 2 (22:05):
Yeah, so that's a really really good question. So kind
of building on your point about monogenic disease, the diseases
where there's a single gene that causes it, there's depending
on how you count, let's say about four thousand of
those that we kind of are well understood, and that
means you have a lot of you have your work
cut out for you just in monogenic disease, and you know,
there's a lot of work to be done there. And
(22:28):
the one thing I'll mention before moving on to the
polygenic is that one of the beauties of the kind
of crisper technology is that, unlike a lot of previous
things that have happened in biotech, the first therapy you
build with a crisper technology is the hardest, and then
the second one gets easier, and the third one gets easier,
and the fourth one gets easier. And that's very different
from a lot of things, like you know, small molecule development,
(22:49):
where every drug you kind of go back to the
starting board and you're like, Okay, well I got to
kind of go through the whole process again, and I
haven't you know, obviously I've learned something, but I'm not
going to like shorten the process for the second small
male the third small molecule I make. And with Christopher,
that's very very different because you're using the same technology
and you're switching out this thing that's called a guide RNA.
You can kind of think of it as like you
go to Google and you type into the search engine
(23:11):
and the guide RNA is what you're typing. So it's
very kind of facile to switch these things out. And
I think that means that even though there are four thousand,
you know where monogenetic diseases, I think we have a
real shot at tackling them all because the first one
is the hardest and it only gets easier from there.
And that's very different from classic biottech.
Speaker 1 (23:30):
Now, how about the polygenetic diseases.
Speaker 2 (23:32):
Right So on the polygenic side, I think the main
challenge there is in an exciting way, going to become
what to edit. So there are limitations to what we
call multiplex editing. Right now, I think the state of
the art would be, you know, you could reasonably do
maybe three to five edits in one go, depending on
(23:52):
which lab you want to kind of take a queue from,
And there's a lot of progress that can be made there,
of course, But even for these things where you're trying
to edit multiple genes, it's often very unclear. Even if
you want to edit five things and you said, hey,
I can go edit five things, like which five you
should edit can be very very tricky, like schizophrenia being
a classic example, even things like type two diabetes, and
(24:15):
there I think there's a lot of progress that could
potentially be made in terms of mapping these diseases and
really understanding even like are these edits additive, Like if
I edit five things, am I getting just the full
benefit of every edit? Or maybe is there a sequence
of edits that's going to be more beneficial if I
do them in a certain kind of cohort together. And
these are very complicated statistical questions, right, and it's very
(24:38):
non obvious kind of what the answer is for many
of these diseases. And that's where I think there's a
lot of additional kind of statistical work that could be done.
Speaker 1 (24:47):
Okay, got it, But you've got the technology now to
go in there and do these experiments. What do you
see as the ethical issues about a society that knows
how to edit genes? As we move forward, Let's say
we're thinking ten years in the future, two twenty years,
what do you see is the issues there? Yeah?
Speaker 2 (25:02):
Well, I think the exciting thing is that we're quickly
going to live in a society where we're better at
making edits in any cell in the human genome than
we are understanding what to edit, which also has to
read out on. Yeah, your question about the ethics of like, Okay,
let's move beyond monogenetic disease. Let's even move beyond like
the classic polygenetic diseases like schizophrena, type two diabetes. I
(25:25):
think these are relatively non controversial things where of course,
if you have an ability to cure people, yeah, you
probably should, or at least I feel very strongly personally
that you should. And then it gets into the realm
of I think, you know, people like to think about, oh, well,
what about things that are not necessarily diseases, but maybe
you want to improve, like whether that's uh, you know, kids,
(25:46):
athleticism or intelligentism and intelligence.
Speaker 1 (25:48):
These are the classic ones.
Speaker 2 (25:49):
And as someone that did a lot of work on
the kind of genetic side of the equation, I think
one thing that's often lost here is that there's no intelligence.
Just to be clear, Like the gains you can get
even from doing a lot of it, it's on the
intelligence side are kind of shockingly minimal.
Speaker 1 (26:08):
Agreed. Although, although if we fast forward twenty years and
you've figured out, hey, polygenetically, here's some very clever AI
way to test this and try that, maybe we'll find
out Oh it's.
Speaker 2 (26:18):
Yeah, it's definitely definitely possible. I think there's a bit
of a holy war in terms of, you know, the
environmental component versus the innate genetic component.
Speaker 1 (26:25):
But the innate genetics doesn't hurt right.
Speaker 2 (26:27):
Right, So let's put that aside for a second and say, okay,
let's just same. There's been progress made, and we have
some better understanding maybe of at least what are the
best possible dits you could make. I think there it's
going to be really interesting because if you zoom out,
I feel like this is, first of all, this is
a question beyond any individual and beyond any company. It's
really kind of a society level question where there's you know,
(26:49):
religious and you know, ethical and kind of personal and
of course corporate kind of viewpoints here. But I think
you've seen this in other deep tech areas. You see
it with AI right now, every country is going to
have kind of a different view on this. And I
think the really interesting thing when you start thinking about
human biology, which we all share, of course, is that
(27:12):
these decisions very much are not in isolation, right, And
it does make you wonder if one country is more
willing to kind of go down some of these paths
that other countries might find less ethical, does that create
an imperative for other countries just to fall along to
stay competitive. And I don't know what The answer to
that is, but I think that's the part that seems
(27:35):
like it might be most complicated, honestly, is different countries
will come to different conclusions, and there's definitely been a
lot of work to try and come to like international
consensus around these things. But in general, I think that's
going to be the trickiest pressure is that even if
let's say in the United States, we make, you know,
certain decisions around this is the line, We're not going
to do edits for intelligence, but we are going to
(27:56):
do edits for anything that's you know, classified as a disease.
Maybe another country decides, hey, actually I want to give
my population super charging powers to whatever extent I can,
and maybe it's a minimal extent, but we're going to
try our vest I think that creates a pretty interesting
situation geopolitically about like how do you handle that?
Speaker 1 (28:15):
Yeah, agreed, once we're a species that knows how to
modify our code. Yes, So the geopolitical things, what do
you think it means just in terms of what it
means to be a human? How does that change? I mean,
let's say we're thinking fifty years in the future here,
and you get to choose everything about your kids and
(28:38):
perhaps yourself in some ways. But how does that change society?
Speaker 2 (28:42):
Yeah, I think it brings to mind one of my
favorite movies, Gatica. I'm sure you've seen it.
Speaker 1 (28:49):
I have seen it, but I thought that was it
was silly in the sense that, just as a reminder
to the listeners, your genes predispose you to some particular
career in that movie, and if you have these genes,
are going to be this kind of janitor or whatever
as opposed to the astronaut. And of course, with the
nature nurture debate, that's totally dead because it's always both so,
(29:13):
but yeah, tell me why it reminded you of Ghika.
Speaker 2 (29:15):
Yeah, because the part there was most salient to me,
I think was this idea that let's say one child
was kind of quote unquote natural born, the other child
was given these certain advantages to whatever degree at birth,
and more to the point, being natural born was just
a disadvantage you weren't allowed to apply to be like
an astronaut, like doors were just closed to you, basically,
(29:35):
And I think that is a very kind of concerning
world to live. I don't want to live in that
world in all honesty and I think you could maybe
have like some rationalist argument about why maybe you should
do that, but I think just morally and ethically, that
feels just really horrible to me. And the whole point
of the movie was that actually, no matter how good
the sciences at that point, there's just certain factors that
(29:58):
make that a silly choice, just the resilience of the
individual and their ability to overcome the challenges they had genetically.
And I think that's a very that's a message that
really resonates with me, because I think even fifty years
from now, there's gonna be many things we don't understand
about our biology. And I think if you try and
overrationalize these things and shut doors because like oh, someone
had this genotype and not that one, just inherently you're
(30:19):
going to be missing things and you're not going to
be actually as rational as you think.
Speaker 1 (30:23):
Well, that's true, but maybe one hundred and two years
from now will be less bad at that. It would
be just by Devil's advocate. It would be like saying,
you know, athletes are on anabolic steroids won't ever be
better than natural athletes, but they will be they can
lift more and so on. Well, yeah, now, there's gonna
be the Enhanced Olympics. I suppose, yeah, exactly so. But
(30:46):
but that doesn't affect the career choices like in Gatica.
Speaker 2 (30:51):
Yeah, I think it's where I think where I get
missed squeamashes when it comes down to like the individual choice,
because going on the athletics example, you can choose to
take performs enhancing drugs or not, right, and that either
shuts through a pensors for you. I think the thing
that's more human to me is you don't choose how
you're born, right, That's a choice that's made for you
in a lot of different ways. And I think that's
(31:11):
where the type of world that I don't want to
live in is where things that are truly outside of
your control in terms of like your your genome before
you even born, determine kind of how you live. And
that's that's not something where I can reconcile personally.
Speaker 1 (31:29):
I mean, interestingly, we're already in that situation, right, which
is that there's a genetic lottery and you show up
in the world with advantages or disadvantages. But now it's
just a matter of whether your parents did the right
payments and edited.
Speaker 2 (31:43):
Well and I think that's an important point as well.
I don't want to live in a world where there's
a massive stratification between the rich and the poort, not
just from like a starting point of like, okay, these
are the opportunities available to you in terms of schooling,
but oh, this is the starting point for you in
terms of your genome. Yeah, and that's something that we
talk about the inheritance of wealth. Well, you literally inherit
(32:05):
your genes. Yes, So that's something that could be a
very durable advantage in some ways if it's not, you know,
something that we think about very deeply before we go
down that path. If we go down that path.
Speaker 1 (32:17):
So following up on that, can we change features in
adults as in you make a change again in the
future where you decide, hey, now I want to be
like the equivalent of performance enhancing drugs and do that
at any age.
Speaker 2 (32:29):
Yeah, And I think that's kind of where the most
of the focus is now, is like, well, first of all,
for disease, of course, you know, let's say someone was
born with Huntington's and now they're in their twenties, like
you want to help them out and really, you know,
prevent them from how any problems in their thirties. I
think for a lot of diseases, one of the key
questions you have to answer is like when do you
have to intervene For some diseases, maybe it could be
(32:51):
very early in life. Maybe there's certain biological processes that
just take place early in life and you need to
do the edit before then, or else maybe you have
to come up with some other way of reversing the disease.
I think, fortunately for seems like maybe most diseases you
can edit an adulthood and that can actually have a
very material effect on the disease. But that isn't going
to necessarily always be true.
Speaker 1 (33:12):
Okay, got it. And so coming back to this conversation
about what society will become, it may be that some
of it is not an issue that you're born with
and you have to deal with, but that you make
a choice, just like anibolic steroids, that people are doing
it that way. Do you suppose that people are going
to be looking for things that involve longevity as one
(33:34):
of their first aims with this.
Speaker 2 (33:36):
Yeah, I mean, obviously there's a huge amount of interest
in longevity. I have a personal interest in living a
healthy life. For a long time anyway. I think I'm
definitely fall more on the spectrum of like health span
versus life span. If I'm living to be two hundred,
but i'm you know, de crefit and can't remember my kids,
that's not a life I personally wanted to live. But
if I live to a very healthy one hundred and
ten and where you know, I die in my sleep,
(33:58):
that sounds great to me. So I think longevity is
definitely an area where gene editing could play a huge
role in terms of you know, what are the processes
is like, you know, some sort of mutation accumulation in
certain areas that's like causing these cells to age in
the way they are, and could we reverse that with
genetic editing approaches. I think that is a very reasonable
(34:18):
and potentially promising line of research. I think that in general,
some of the biggest longevity things we can do though
today is like, you know, heart disease like cancer obviously
being a big one, and those are of course directly
addressable by genetic editing as well. And it goes to
interesting questions of like, should we edit millions of people
(34:39):
in the US to reduce their risk of heart disease
by thirty percent. That could say tons and tons of lives.
It's a relatively large in invention for them. So obviously
you'd have questions about safety. So far, crisper seems to
be very very safe at least based on the trials
and humans so far. So that's something we could do.
Is that something we want to do as a society?
Speaker 1 (34:58):
What would be the pros and cons?
Speaker 2 (35:00):
So the pro would be you reduce let's say hard
tech and it all cause mortality essentially and a huge
segment of the population. The con would be there's going
to be some expense associated with that. Do we want
to pay that expense as a society? Maybe it saves
us money in the long term because both people are
more productive and you're also spending less and kind of
in stage care in the hospital.
Speaker 1 (35:21):
And then see that as a government program that's paid
for as opposed to individuals saying, hey, I'm going to
pay for this.
Speaker 2 (35:26):
Well, I think that's a very interesting question as well,
and I think you could see stratification there of maybe
you know, frankly wealthier individuals choosing to get a lot
of these types of technologies, whereas you know, is that
available to everyone. That's the kind of choice for society.
And then of course the big one would be safety.
You only want to do that if it's extremely safe, right,
because you're trying to prevent disease kind of an aggregate,
(35:49):
so it needs to be extraordinarily safe for each individual.
Speaker 1 (36:10):
Do you think if you're interested in longevity, do you
think you're going to see this in your lifetime where
there are edits that can be made Let's say forty
years from now, where you say, hey, this is great,
I'm going to live longer. I'm going to expand this.
Speaker 2 (36:23):
Yeah, it's an interesting question. I wouldn't be surprised if
there's things that can maybe get you ten to twenty
percent further along. Are we going to see like a doubling.
I mean, that'd be great. Sure, I'm not going to
be root against it. I would be surprised. Frankly, we've
run a natural experiment. There's billions of humans on Earth
with all sorts of genomes. No one seems to live
(36:46):
over one hundred and ten hundred and twenty. Let's say
that doesn't mean you know, it's not possible, but I
think that one of the areas where I think we'll
see way more progress on is like health span within
that period. So like if you can live to an
extraordinarily healthy one hundred ten where you're hiking mountains and
you're having fun with your kids, that's already a huge
extension of that's like a twofold extension of life relative
(37:08):
to what a lot of people really kind of practically experience.
And I think glip ones and things like that, the
obesity drugs from the Lili and Novo and others, I
think that that's also kind of u shown that there
can be these kind of giant mass markets in biottech.
And longevity is the other one that everyone always kind
of thinks about, but there's others as well. You can
(37:30):
imagine things that mitigate like alcohol consumption or you know,
other areas. I don't I don't think glip ones are
going to be the only kind of trillion dollar drug
in biotech, but I think it's the first, and I
think hopefully that kind of inspires everyone else in biotech,
including us at Mammoth, to really think more broadly and
more fundamentally about, Okay, what are the things we can
do that actually change society for the better overall, not
(37:51):
just necessarily for specifical you got to start with specific
things and knock out rere diseases. But I think in
terms of like the long term vision of Mammoth, I
think that becomes very very exciting.
Speaker 1 (38:01):
And I've been throwing out numbers like three years, five years, ten,
But what you see, given your incredibly specific view on
what is happening right now, what you're capable of doing,
what is that time scale that we're talking about.
Speaker 2 (38:16):
Yeah, so I mean, going back to the beginning of
the conversation, Already, today people are being treated for sickle
cell disease using crispers.
Speaker 1 (38:24):
That's today.
Speaker 2 (38:25):
I think over the next five years, for the tissues
that are kind of most easily accessible, like blood and liver,
people are going to be shocked at how much progress
is made at curing rare diseases in those areas. And
these are kind of things where it's like it happens
slowly and then it happens all at once. It's very
much like that. And then I think over the next
ten years, you're gonna, because of you know, Mammoth, be
(38:49):
able to see us knocking out diseases and like muscle
and brain and all the other tissues of the body,
and I think it's going to take time, and there's
a lot.
Speaker 1 (38:58):
Of diseases to go through.
Speaker 2 (38:59):
But I think if we're sitting here a couple decades
from now and people are still suffering from rare disease,
we've done something incredibly wrong, Like things have gone off
the rail somewhere, and that's insane. Like to live in
a world where genetic disease is really a thing of
the past would be transformative for those patients, but also
I think for society generally. And I think once you've
(39:20):
done that, that's when you in parallel, because now you're
showing the safety, Now you're showing that this is an
effective technology. I think you can start to dream even bigger.
You can start to think about, like, you know, how
do you go after reducing cardiovascular risk, how do you
go after even more esoteric things like thinking about health span,
Like there's certain people that have short sleep and they
(39:41):
actually only need to sleep like three to four hours
a night, Like what if we could all do that?
Speaker 1 (39:45):
Right?
Speaker 2 (39:45):
Like just really thinking about how do we transform society
for the better and kind of more aggregate ways. That's
really long term where I get very excited.
Speaker 1 (39:55):
Unlike traditional medicine, which addresses symptoms of disease, gene editing
technology in general could change really fundamental aspects of who
we are. And so what do you think this does
to personal identity? Yeah?
Speaker 2 (40:09):
I think to your point, this is a very different
way of doing medicine. Like often medicine is treating symptoms,
often very effectively, but really treating symptoms, whereas this is
going into the core, into your DNA and really solving
the problem at it.
Speaker 1 (40:24):
Right, But I mean not just helping with disease, but
enhancing humans, changing who we are. So yeah, what does
that do to our sense of personal identity? Yeah?
Speaker 2 (40:33):
I think it's definitely something where we have a deep
kind of personal identity obviously in terms of how we think,
how we act, how we dress, and I think long term,
just truly thinking like one hundred years here, maybe we
start to think more of our genomes as our clothing, right,
Like we think of our clothing as representing our personal identity.
(40:54):
And that's fine, and that's something people embrace, and people
of all sorts of different styles and things they do.
But right now, that's not very much how we think
of our genomes. But if genomes become malleable, and they
become something where you really do have this option of
kind of choosing what things you want to keep or change.
Maybe we start to see that more as kind of
extension of ourselves. That's not core in the sense of
(41:17):
it can never change, but core in the sense of
I want that to reflect who I am as an individual,
and I have the choice of how that looks.
Speaker 1 (41:23):
Oh, that's great. Yeah, in the same way that someone
might go off and get blonde hair for a while
and red hair and dark hair and change color their
eyes or whatever. There are ways of doing the stuff now,
and there's can be better ways or more direct ways
of doing it. What do you suppose that means in
terms of motivation and earning something like, for example, I
go to the gym and I lift weights. It's really hard.
But if I could go and.
Speaker 2 (41:44):
Sure you get your miostatin gene blasted and you just
have a huge muscles from setting home on the couch.
I think that's an interesting question at the society level,
because why do we care about muscles? Why do we
care about other things? Like at other times in society,
having pale skin has been something that people value. I
mean still today in many places, and it's because oh,
you don't have to go work in the farms, and
(42:04):
that means you're a high class individual with a lot
of money. Or in some societies even today and in
the past, being very overweight was a sign of high
status because you're not starving. And I think that what
that could mean, and this is just like you know,
purely hypothesizing, is maybe being healthy remains an important thing,
(42:25):
but it's not a reflector of status in the same
way it is today, which would be awesome, Like what
if actually everyone is walking around super healthy, Yeah, amazing,
But maybe that means that there's less of a status
differentiator of oh, this person has time to go to
the gym and they work very hard, so something else.
But you're humans, right, we love Frankly, it seems to
stratify ourselves based on status. So some new thing will
(42:47):
come up and it'll be like, oh, they have a
blue hat. That's the sign of, you know, high status,
and we could pass the judgment on whether that's good
or bad. But I think that's probably what would happen,
is that it just means that a society is better
off overall because everyone's very healthy and has the right
amount of muscle, but there's a different status game being
played in terms of you know, when you go to
the club on a Friday or whatever.
Speaker 1 (43:13):
That was Trevor Martin, co founder and CEO of Mammoth Biosciences,
We talked about the emerging tools that allow us to
edit life at its most fundamental level, the conversation and
the tools he's building. This allows us to look at
the near future in which we can slice out chunks
of the genome, or rewrite individual letters, or even fine
(43:37):
tune the expression of genes without altering the sequence. And
eventually this gives us finer and finer control over our
biological destiny in ways that we're only beginning to understand.
Because these technologies are not going to only give us
the chance to fix mutations, They're going to expand what
(43:58):
is possible. They will read find the relationship between who
we are and who we might become. Where we stand
now is in a field of question marks that no
single thinker can answer alone. Questions about the line between
therapy and enhancement, between responsibility and hubris, between embracing the
(44:21):
malleability of life and respecting everything. We don't understand about it,
Only one thing seems certain. At this point, we are
no longer just passengers on evolution's very long and winding road.
We are taking the wheel, and with that power comes
a great responsibility, the weight of choices that are going
(44:43):
to ripple through generations, the weight of choices that will
shape the genetic landscape of those who come after us.
In the end, our role is going to be to
learn how to annotate the book of life with great care,
to correct its most tragic errors while preserving the poetry
(45:03):
of its imperfections. We now see the genome not as
a finished book, but instead as a draft in progress,
and that compels us to constantly ask ourselves, how much
of the story should we change? What kind of story
do we want to tell? And how can we be
the most careful custodians of the possibilities. Go to Eagleman
(45:31):
dot com slash podcast for more information and to find
further reading. Send me an email at podcast at eagleman
dot com with questions or discussion, and check out and
subscribe to Inner Cosmos on YouTube for videos of each
episode and to leave comments. Until next time. I'm David Eagleman,
and this is Inner Cosmos.
We are defined in large part by the genomes that
we happen to come to the table with. So what
does it mean when we can edit our own genomes?
What does this have to do with viruses or copy pasting,
or whether we are going to modify the story of
our own species. This is in our cosmos, and I'm
(00:29):
David Eagleman. I'm a neuroscientist and author at Stanford And
in these episodes we sail deeply into our three pound
universe to uncover some of the most surprising aspects of
our lives. Today's episode is about the remarkable situation we
(00:54):
find ourselves in, which is that we now know how
to read our biological inheritance. Now, this is very easy
to take for granted because for most of us this
has been true for our whole lives. But it's a
very recent ability for our species. It only began in
the second half of last century. In my postdoctoral fellowship,
(01:17):
I worked with Francis Crick, who was the co discoverer
of the structure of DNA. In April of nineteen fifty three,
he and James Watson published a paper in Nature, and
in just over a page they proposed the double helix
structure of DNA, explaining how genetic information is stored and copied. Now,
(01:41):
there's something about this paper that always makes me tear
up when I read it, because the insight changed our
world and almost certainly the future of our species. What
they realize is that DNA is made of two complimentary
strands wound around each other, and the bases are which
just means A on one strand always links with T
(02:03):
on the other, and C with G. And this gives
a mechanism for making a xerox copy of the whole thing,
because you just unwind the two strands and then each
serves as the template for sticking on new bases in
the right spots. But what I want to emphasize is
how new this is. Nineteen fifty three, isn't that long ago?
(02:24):
World War Two was over, Eisenhower was president of the US,
and by this point we already had automatic transmission in
cars and color television and microwave ovens. But we had
no idea why your ears look like your father's ears,
or your eyes look like your mother's eyes. Just imagine this,
(02:46):
before the discovery of the DNA code, how difficult it
was to understand how inheritance actually happens biologically. People floated
all kinds of wacky hyppods disease about it, like maybe
each sperm cell contained a super tiny embryo. But everyone
(03:07):
knew these models didn't work. And even while people were
driving cars and watching TV and microwaving, they knew that
inheritance was a total unknown in science. And then that
all changed with that very short paper that laid the
foundation for modern genetics and molecular biology and ultimately technologies
(03:31):
like gene editing, and so that puts us where we
are now. For as long as animals have walked this earth,
we have been shaped by forces beyond our control, by
the slow hand of evolution, by the accidents of mutation,
by the blind winnowing of natural selection. The twisting helix
(03:53):
of our DNA has been sculpted by nature's chisel. But now,
for the first time, we are holding the chisel in
our own hands. Just in the last nanosecond of evolutionary time,
we now command gene editing technologies, things like crisper and
(04:15):
single base pair editing tools and epigenetic editing tools and
tools yet to be imagined, and these give us the
power to rewrite the code of life itself. We can
correct genetic disorders, we can eliminate inherited diseases, and we
can presumably even enhance ourselves, pushing beyond the biological boundaries
(04:41):
that we would have recently assumed are fixed. The rules
of genetic inheritance were once immutable, but now they are revisable.
So obviously, with this power comes deep questions. If we
can edit our genetic destiny, what should we choose to become?
(05:03):
Do we cure only what ails us? Or do we
optimize ourselves enhancing features like intelligence and strength and longevity.
How close are we to doing any of this? Does
anything happen to the meaning of human struggle? When suffering
can be edited away? Will we remain the same species
once we begin sculpting ourselves? And who decides is it
(05:28):
the scientists at the lab bench, the policymakers and government,
the parent holding their newborn in their arms. What are
the ethical and social and existential questions of putting our
genetic future in human hands? So in today's episode, we're
(05:48):
going to step into the frontier of gene editing. What
does it mean to be human when we are no
longer bound by the limits of our biology. What stories
will future generation tell about the choices that we make?
Now the code of life is no longer written in stone,
so what will we write? So I called my friend
(06:10):
Trevor Martin, who is the co founder and CEO of
Mammoth Biosciences, which is based here in the San Francisco
Bay area. They are building the next generation of Crisper
products for editing the genome. If you've never heard of
Crisper or aren't sure what it is, hangtight because we'll
get to that in a minute. But the quick preview is,
how do you build a platform to read and write
(06:34):
the code of life? How do you make tools? So
you get something like a word processor for the genome
where you say, look, I just want to hit control
X to cut a piece of the genome, or control
V to paste it, and control F to find some
sequence inside the genome. So here's my conversation with Trevor Martin.
(07:00):
Technology is some of the most amazing technology we have,
but it wasn't actually invented by humans. It was merely
discovered by us. So tell us about that, tell us
about Crisper.
Speaker 2 (07:08):
Yeah, So, similar to how we have immune systems, actually
bacteria and small microbes and just teny little organisms. They
have to defend themselves against invasion as well. Typically viruses
actually much like us, and one of the ways that
they evolve to do this is this thing called crisper
that has become famous, of course for its ability to
(07:30):
do genetic editing. But fundamentally nature has used these crisper
type systems to protect themselves from viruses, very similar to
how our adaptive immune system protects us from viruses.
Speaker 1 (07:42):
And we've kind of ripped that out.
Speaker 2 (07:44):
Of nature and done a ton of engineering on top
of it to turn it into these technologies that can
do genomic engineering. But that's kind of fundamentally where it
came from. And I think it's this beautiful example of
leveraging billions of years of evolution and combining that with
human ingenuity and a lot of hard work from a
lot of scientists.
Speaker 1 (08:04):
So let me get straight. So, so crisper if fits in,
Let's say a single cell organism, a virus injects some
DNA and it's got to figure out, hey, that's not mine,
and then it cuts it up exactly.
Speaker 2 (08:14):
So there's a bunch of complicated steps there. First, it
has to recognize Hey, that's not mine. Then it has
to cut it up. And then actually there's a third step,
which is, hey, I should remember this came and i'd
want to make sure I protect against it in the future.
And it's actually funny, that's where the name crisper itself
comes from, is that I want to protect against the future.
So CRISPER is actually an acronym stands for clustered regulatory
(08:35):
interspace short palindromic repeats and this is actually kind of
the memory of the cell that the crisper systems used
to say, Hey, these are viruses that have invaded me before,
and I want to make sure they don't do it again.
Speaker 1 (08:48):
And this happens in unicellular organisms. That's so incredible, Okay,
And so you started this company Mammoth with the idea
to take these crisper systems and I prove them from
what nature has done or search for other ways of
doing it. So give me a sense of how you
do that. Yeah.
Speaker 2 (09:06):
So probably the most famous Chrisper system is this thing
called CAST nine. And this was what one of my
co founders, Jennifer Dalna, won the Nobel Prize for a
few years ago. Was the work in terms of really
characterizing and developing this into a geneomic engineering technology. And
CAST nine was just one example from a certain class
of bacteria of this type of crisper technology. And one
(09:30):
of the fundamental insights of Mammoth is that actually, there
are all sorts of Christopher technologies out there, because these
are present and all sorts of microorganisms, bacteria, even large
viruses archaea. And our insight was, hey, we should look
through all of these alternative versions of crisper that are
not CAST nine and do a lot of work to
(09:50):
develop those, and that could actually have a huge benefit
for building genomic medicines, for building diagnostics, for improving agriculture.
And that was kind of a fundamental insight that was
maybe obvious today, but at the time people were so
focused on CAST nine that people weren't really looking beyond that.
Speaker 1 (10:06):
So you're looking for things that have already been discovered
by nature elsewhere, and you're looking for versions of that
that do what you want in terms of gene editing.
Speaker 2 (10:17):
So the trick there is that you use nature as
a starting point. And the unfortunate truth is that when
you take these things and you rip them out of nature,
actually usually they don't work at all, but they give
you a starting point. And one of the fundamental insights
we had was it's not enough just to go into
nature and to say, ah, okay, what other alternative crispers
are there? You have to do that, and then you
have to do a ton of engineering. And we actually
(10:39):
have a whole floor of our building that has these
liquid handling robots. They're just running tens of thousands of
experiments at a time and you just kind of grind
away and you can use the latest AI techniques combining
it with the latest and microfluid candling is what those
robots are called. And it's only with that combination of
all of that, with this kind of usually very wacky,
kind of natural starting point. That's the secret sauce one
(11:00):
or the other is not enough. You have to really
have both together. And that was the unique insight as well.
Speaker 1 (11:04):
Oh great, okay, And so they're looking for these smaller systems,
and what's the reason to have them smaller?
Speaker 2 (11:11):
Yeah, So one of the giant challenges of the field
is how do you deliver these systems to the cells
that need it the most. So when you and I
think about genetic medicine, what comes to mind, it's going
to be things like Alzheimer's, Parkinson's, Huntington's, you know, these
really debilitating disorders where they can be basically a death
sentence and you something that's kind of known in your
genome from birth. And the big problem though, has been
(11:35):
what the genetic medicine, the crisper field has been focused
on is a tiny subset of diseases that are typically
not that and that's amazing for those patients that have
diseases that are like blood disorders or like certain liver disorders,
and there's amazing progress in this field, like for example,
there's now an approved therapy using Crisper for sickle cell
disease in beta talasmia. Those are overlook diseases with underrepresented
(11:56):
populations and that's a huge win for the field. But
the proms of genetic medicine is not just blood disorders
and liver disorders. The promise is to go to any
cell in the body and do any kind of edit.
And that really is what guides us at Maamath that
means you need to go to the muscle, you need
to go to the brain, you need to get to
the heart. And that has been a gigantic challenge, and
it's because CAST nine is actually a big protein. So
(12:19):
obviously it's small relative to us, like all proteins, but
it's really really big on a kind of molecular scale.
And one of the things that we did is we said, hey,
could we create a crisper system that's not just a
little bit smaller than CAST nine, but it's way smaller.
And that resulted in a thing we called nanocasts nano
and that was really exciting and there's a lot of
(12:40):
skepticism in the field, which is great for our patents,
people like, oh, these will never work. And it required
a ton of work and a lot of these robots
doing a lot of work overtime with our scientists. And
what's cool though, is that now we actually have data
showing that in monkeys, which is a really high bar.
It's not you know, cell lines or mice, we actually
get extremely good editing either equivalent or better than CAST
(13:04):
nine with these really really tiny systems. And these really
tiny systems, unlike CAST nine, can actually be delivered anywhere
in the body, so that's a seed change in terms
of what's possible.
Speaker 1 (13:14):
And they can be delivered by a virus for example.
Speaker 2 (13:17):
Yeah, So a classic way that you can deliver to
muscle or brain, for example, would be with a thing
called AV which is another acronym that stands for adno
associated virus. And one of the big limitations of this
is that it has a very strict size limit. Like
you can think of it as like a semi trailer
truck where you can only fit so much in the
back and cast nine is just way too big to
(13:38):
fit inside it. But these nanocast style systems don't just fit,
but they actually have a ton of room to spare.
And the room to spare is really important as well,
because when you're a scientist you can start to think
really creatively about how do I use that. And one
of the key ways that we use that is to
fit in the machinery to do different types of edits.
So people may have heard of things like base editing
(13:59):
or writing or epigenetic editing. These are all techniques that
take the fundamental Chrisper system and say, hey, what if
instead of editing the genome as this like word document
and only being able to delete sentences, what if we
could add a paragraph, What if we could spell check
a word? What if we could italicize a sentence. These
are all kind of different types of edits you can
(14:21):
do in the genome, and they require delivery have even
more machinery, and that means that Mammoth has really been
the only company that's been able to actually deliver not
just anywhere in the body, but also deliver any kind
of edit anywhere in the body. And I think it's
you have to do both of those if you really
want to address all genetic.
Speaker 1 (14:37):
Disease, and any kind of edit means reading or writing. Yeah.
Speaker 2 (14:42):
So we also had a lot of work we did
on diagnostics as well, and during the pandemic we actually
got emergency use authorization for a Chrisper based COVID test.
So we're super proud of the work we did there.
The focus of the company today is very much on
the writing side, but definitely I think there's huge potential
on the reading side.
Speaker 1 (15:00):
As well. Give us an example of the reading side.
Speaker 2 (15:04):
Yeah, so basically there, instead of using the Chrisper systems
to change the DNA, you can use the Chrispher systems
to send out some signal that there's a certain sequence present,
so to say, hey, I found the word potato and
it'll glow green if it finds potato, and it won't
show any color if it doesn't. And that's a very
(15:24):
powerful kind of concept, and that means you could do
really low cost, high accuracy style molecular testing, and that's
something that we're very bullish on long term. But as
a company, obviously you have to focus on a certain area,
and already, you know, trying to tackle all genetic diseases
a limited set of focus to begin with, So that's
(15:45):
kind of kind of where we're focusing our efforts otherwise.
Speaker 1 (15:48):
Right, So let me come back to something you said. So,
as far as the writing goes, you can write single
base pairs, you can write something longer. You can write
whole genes or collections of genes. Ice.
Speaker 2 (16:00):
Yeah, you could have all insert an entire gene. You
could kind of change a single base pair out of
all the billions of base pairs in your genome. And
that's an important philosophical point as well, because I think
in biotech we often get so enamored with technology, so
we always think in terms of like, ah, this is
a base editing technology, or this is a gene writing technology,
This is like Deuvile's trand break if you're patient. You
(16:22):
don't care, Right, I have a disease and I don't
care how you're doing it. I just want you to
cure or treat my disease. In our case, we can
actually cure it. And I think that's where our philosophy is.
Will actually develop many techniques, all the techniques, and actually
be able to deliver them. And then for any disease,
we might try a couple of different ways of doing it.
(16:42):
We might say, ah, there's like a way to do
it by base editing, there's a way to do it
by epigenetic editing. We're not sure which one's gonna be
the best, but we'll try both and see which one
actually works well. And that's very different from philosophy from
typical biotech, where you try and create like ten companies
whe each company is doing a different method and I
think that's all fine and well in some ways, maybe
also from like how do you maximize like investor involvement
(17:06):
in different companies, But from a I think long term
company building and from a patient perspective, I think that's
very much like the wrong way to go about it.
Speaker 1 (17:14):
Yeah, So tell us about diseases in the brain and
what you're thinking of, is the future of those maybe
in give me a sense of three years, ten years
where we'll be with that. Yeah.
Speaker 2 (17:25):
So to start with a specific example of one that
I think kind of is frankly a condemnation of the
genetic medicine space is Huntington's disease. So this is a
disease that was mapped, Oh my god, not just decades ago,
like half a century ago, like I think in like
the late eighties, and it was mapp They mapped it
with microsatellites, I believe, on giant gels that were in
(17:46):
the lab. Right, this is like, you know, not pre computer,
it's like Wexler, right, Yeah, but you know, very very
early technologies, and we have understood, you know, fundamentally kind
of the genetic base of Huntington's for a very long time,
and still today people die from this every single year,
and it's a horrible disease where basically, if you have
a certain genomic sequence, then you know, typically in your thirties,
(18:10):
you'll have the accumulation of a certain protein and you'll
pass away. And it's infuriating, honestly that we understand the
genetic cause of this and we can do nothing about it.
So I think the genetic medicine space and Crisper in
particular will have arrived and will have really I think,
done a hallmark deliverance of like what the true potential
(18:33):
is the day the last Huntington patient dies?
Speaker 1 (18:35):
Agreed? When is that? Do you think?
Speaker 2 (18:37):
Yeah? So, I think it's definitely within sight. I'm not
going to give a specific.
Speaker 1 (18:42):
Three years or five or ten.
Speaker 2 (18:44):
Yeah, it's probably not three, but it better not be ten. Okay, Yeah,
I think in general, like you can kind of see
the steps that you need to take and it's a
matter of walking down the path.
Speaker 1 (18:55):
Got it? And what has been the problem? Given that
we have Chrisper cast technology and that we have known
the gene for Huntington's it's monogenetic, what has been the
hold up? Yeah?
Speaker 2 (19:05):
So I think there's a lot of things you have
to think about. One is what type of edit are
you going to do? Like can you just knock out
the whole Huntington gene or do you have to think
more creatively about modifying it in a more subtle way.
Then the second one is can you actually get the
editing machinery to the cells of interest? Can you actually
get this into the brain, and those are two of
(19:27):
the most obvious problems. I think that we've really thought
deeply about mammoth and like the general sense, not just
running to the before any brain disease. And I think
that's where the technologies we've developed, like these ultracompact systems
and having all these different editing modalities I think can
make a huge difference.
Speaker 1 (19:43):
Potentially got it and so it sounds like you've got
the can we get it to the right cells? It
sounds like you've got a beat on that. But as
far as what edit to make is that something you're
experimenting with, well, I.
Speaker 2 (19:55):
Think that's definitely something where we have a lot of
great ideas for any about like different types, and that's
where we're very unique because we can actually try different
methods and we can say, hey, this is our hypothesis,
prove it out or not, but not have a hammer
and everything else to look like a nail, which is
very very classic not just a biotype but a deep
tech in general. And you know the classic startup advice
(20:17):
of like find the problem first and then figure out
the solution. There's a lot of reasons why that doesn't
work in deep tech right, Like, sometimes you really do
have to kind of build the thing and then figure
out what the best application is. But that being said,
the more you can mitigate that, that's a very powerful
idea to get away from hammer, you know, squint at
everything until it's a nail.
Speaker 1 (20:36):
Yeah, let me make sure I understand. What's the way
that you can test out these different hypothesies. Do you
(20:57):
have an animal model of Huntington's.
Speaker 2 (20:58):
Yeah, it's gonna so not speaking specifically about Huntington's, but
just generally in terms of different diseases. Some diseases you'll
have an animal model that's really good, and that means
you can actually try it out like in mice or
maybe even monkeys, and like really get a lot of
confidence for others. Honestly, you don't have anything. Maybe there's
no animal models, so like you have to try it
out in cell lines and then kind of make your
(21:19):
best guess about what's going to work.
Speaker 1 (21:20):
Well.
Speaker 2 (21:21):
So it's very varied, i'd say, across different diseases and
across different tissues, but you want to have as many
shots on goal I think as possible because then when
you go to humans, maybe you'll find something surprising, Like
you only had cell line work and then it doesn't
work in humans. And if you only have one technique,
you're kind of out of luck. But if you have,
like you know, a backup or a backup to the backup,
(21:43):
that means you can actually go in and you know,
do something for patients after that.
Speaker 1 (21:47):
Got it. So that gives us a good sense of
what the challenge is with something like Huntington's. Now, Huntington's
is one gene. If you got it, you're getting Huntington's.
But what about other diseases, whether it's Alzheimer's or schizophreny
or whatever, that are polygenic, I can involve lots of machines.
Does that make the problem exponentially harder.
Speaker 2 (22:05):
Yeah, so that's a really really good question. So kind
of building on your point about monogenic disease, the diseases
where there's a single gene that causes it, there's depending
on how you count, let's say about four thousand of
those that we kind of are well understood, and that
means you have a lot of you have your work
cut out for you just in monogenic disease, and you know,
there's a lot of work to be done there. And
(22:28):
the one thing I'll mention before moving on to the
polygenic is that one of the beauties of the kind
of crisper technology is that, unlike a lot of previous
things that have happened in biotech, the first therapy you
build with a crisper technology is the hardest, and then
the second one gets easier, and the third one gets easier,
and the fourth one gets easier. And that's very different
from a lot of things, like you know, small molecule development,
(22:49):
where every drug you kind of go back to the
starting board and you're like, Okay, well I got to
kind of go through the whole process again, and I
haven't you know, obviously I've learned something, but I'm not
going to like shorten the process for the second small
male the third small molecule I make. And with Christopher,
that's very very different because you're using the same technology
and you're switching out this thing that's called a guide RNA.
You can kind of think of it as like you
go to Google and you type into the search engine
(23:11):
and the guide RNA is what you're typing. So it's
very kind of facile to switch these things out. And
I think that means that even though there are four thousand,
you know where monogenetic diseases, I think we have a
real shot at tackling them all because the first one
is the hardest and it only gets easier from there.
And that's very different from classic biottech.
Speaker 1 (23:30):
Now, how about the polygenetic diseases.
Speaker 2 (23:32):
Right So on the polygenic side, I think the main
challenge there is in an exciting way, going to become
what to edit. So there are limitations to what we
call multiplex editing. Right now, I think the state of
the art would be, you know, you could reasonably do
maybe three to five edits in one go, depending on
(23:52):
which lab you want to kind of take a queue from,
And there's a lot of progress that can be made there,
of course, But even for these things where you're trying
to edit multiple genes, it's often very unclear. Even if
you want to edit five things and you said, hey,
I can go edit five things, like which five you
should edit can be very very tricky, like schizophrenia being
a classic example, even things like type two diabetes, and
(24:15):
there I think there's a lot of progress that could
potentially be made in terms of mapping these diseases and
really understanding even like are these edits additive, Like if
I edit five things, am I getting just the full
benefit of every edit? Or maybe is there a sequence
of edits that's going to be more beneficial if I
do them in a certain kind of cohort together. And
these are very complicated statistical questions, right, and it's very
(24:38):
non obvious kind of what the answer is for many
of these diseases. And that's where I think there's a
lot of additional kind of statistical work that could be done.
Speaker 1 (24:47):
Okay, got it, But you've got the technology now to
go in there and do these experiments. What do you
see as the ethical issues about a society that knows
how to edit genes? As we move forward, Let's say
we're thinking ten years in the future, two twenty years,
what do you see is the issues there? Yeah?
Speaker 2 (25:02):
Well, I think the exciting thing is that we're quickly
going to live in a society where we're better at
making edits in any cell in the human genome than
we are understanding what to edit, which also has to
read out on. Yeah, your question about the ethics of like, Okay,
let's move beyond monogenetic disease. Let's even move beyond like
the classic polygenetic diseases like schizophrena, type two diabetes. I
(25:25):
think these are relatively non controversial things where of course,
if you have an ability to cure people, yeah, you
probably should, or at least I feel very strongly personally
that you should. And then it gets into the realm
of I think, you know, people like to think about, oh, well,
what about things that are not necessarily diseases, but maybe
you want to improve, like whether that's uh, you know, kids,
(25:46):
athleticism or intelligentism and intelligence.
Speaker 1 (25:48):
These are the classic ones.
Speaker 2 (25:49):
And as someone that did a lot of work on
the kind of genetic side of the equation, I think
one thing that's often lost here is that there's no intelligence.
Just to be clear, Like the gains you can get
even from doing a lot of it, it's on the
intelligence side are kind of shockingly minimal.
Speaker 1 (26:08):
Agreed. Although, although if we fast forward twenty years and
you've figured out, hey, polygenetically, here's some very clever AI
way to test this and try that, maybe we'll find
out Oh it's.
Speaker 2 (26:18):
Yeah, it's definitely definitely possible. I think there's a bit
of a holy war in terms of, you know, the
environmental component versus the innate genetic component.
Speaker 1 (26:25):
But the innate genetics doesn't hurt right.
Speaker 2 (26:27):
Right, So let's put that aside for a second and say, okay,
let's just same. There's been progress made, and we have
some better understanding maybe of at least what are the
best possible dits you could make. I think there it's
going to be really interesting because if you zoom out,
I feel like this is, first of all, this is
a question beyond any individual and beyond any company. It's
really kind of a society level question where there's you know,
(26:49):
religious and you know, ethical and kind of personal and
of course corporate kind of viewpoints here. But I think
you've seen this in other deep tech areas. You see
it with AI right now, every country is going to
have kind of a different view on this. And I
think the really interesting thing when you start thinking about
human biology, which we all share, of course, is that
(27:12):
these decisions very much are not in isolation, right, And
it does make you wonder if one country is more
willing to kind of go down some of these paths
that other countries might find less ethical, does that create
an imperative for other countries just to fall along to
stay competitive. And I don't know what The answer to
that is, but I think that's the part that seems
(27:35):
like it might be most complicated, honestly, is different countries
will come to different conclusions, and there's definitely been a
lot of work to try and come to like international
consensus around these things. But in general, I think that's
going to be the trickiest pressure is that even if
let's say in the United States, we make, you know,
certain decisions around this is the line, We're not going
to do edits for intelligence, but we are going to
(27:56):
do edits for anything that's you know, classified as a disease.
Maybe another country decides, hey, actually I want to give
my population super charging powers to whatever extent I can,
and maybe it's a minimal extent, but we're going to
try our vest I think that creates a pretty interesting
situation geopolitically about like how do you handle that?
Speaker 1 (28:15):
Yeah, agreed, once we're a species that knows how to
modify our code. Yes, So the geopolitical things, what do
you think it means just in terms of what it
means to be a human? How does that change? I mean,
let's say we're thinking fifty years in the future here,
and you get to choose everything about your kids and
(28:38):
perhaps yourself in some ways. But how does that change society?
Speaker 2 (28:42):
Yeah, I think it brings to mind one of my
favorite movies, Gatica. I'm sure you've seen it.
Speaker 1 (28:49):
I have seen it, but I thought that was it
was silly in the sense that, just as a reminder
to the listeners, your genes predispose you to some particular
career in that movie, and if you have these genes,
are going to be this kind of janitor or whatever
as opposed to the astronaut. And of course, with the
nature nurture debate, that's totally dead because it's always both so,
(29:13):
but yeah, tell me why it reminded you of Ghika.
Speaker 2 (29:15):
Yeah, because the part there was most salient to me,
I think was this idea that let's say one child
was kind of quote unquote natural born, the other child
was given these certain advantages to whatever degree at birth,
and more to the point, being natural born was just
a disadvantage you weren't allowed to apply to be like
an astronaut, like doors were just closed to you, basically,
(29:35):
And I think that is a very kind of concerning
world to live. I don't want to live in that
world in all honesty and I think you could maybe
have like some rationalist argument about why maybe you should
do that, but I think just morally and ethically, that
feels just really horrible to me. And the whole point
of the movie was that actually, no matter how good
the sciences at that point, there's just certain factors that
(29:58):
make that a silly choice, just the resilience of the
individual and their ability to overcome the challenges they had genetically.
And I think that's a very that's a message that
really resonates with me, because I think even fifty years
from now, there's gonna be many things we don't understand
about our biology. And I think if you try and
overrationalize these things and shut doors because like oh, someone
had this genotype and not that one, just inherently you're
(30:19):
going to be missing things and you're not going to
be actually as rational as you think.
Speaker 1 (30:23):
Well, that's true, but maybe one hundred and two years
from now will be less bad at that. It would
be just by Devil's advocate. It would be like saying,
you know, athletes are on anabolic steroids won't ever be
better than natural athletes, but they will be they can
lift more and so on. Well, yeah, now, there's gonna
be the Enhanced Olympics. I suppose, yeah, exactly so. But
(30:46):
but that doesn't affect the career choices like in Gatica.
Speaker 2 (30:51):
Yeah, I think it's where I think where I get
missed squeamashes when it comes down to like the individual choice,
because going on the athletics example, you can choose to
take performs enhancing drugs or not, right, and that either
shuts through a pensors for you. I think the thing
that's more human to me is you don't choose how
you're born, right, That's a choice that's made for you
in a lot of different ways. And I think that's
(31:11):
where the type of world that I don't want to
live in is where things that are truly outside of
your control in terms of like your your genome before
you even born, determine kind of how you live. And
that's that's not something where I can reconcile personally.
Speaker 1 (31:29):
I mean, interestingly, we're already in that situation, right, which
is that there's a genetic lottery and you show up
in the world with advantages or disadvantages. But now it's
just a matter of whether your parents did the right
payments and edited.
Speaker 2 (31:43):
Well and I think that's an important point as well.
I don't want to live in a world where there's
a massive stratification between the rich and the poort, not
just from like a starting point of like, okay, these
are the opportunities available to you in terms of schooling,
but oh, this is the starting point for you in
terms of your genome. Yeah, and that's something that we
talk about the inheritance of wealth. Well, you literally inherit
(32:05):
your genes. Yes, So that's something that could be a
very durable advantage in some ways if it's not, you know,
something that we think about very deeply before we go
down that path. If we go down that path.
Speaker 1 (32:17):
So following up on that, can we change features in
adults as in you make a change again in the
future where you decide, hey, now I want to be
like the equivalent of performance enhancing drugs and do that
at any age.
Speaker 2 (32:29):
Yeah, And I think that's kind of where the most
of the focus is now, is like, well, first of all,
for disease, of course, you know, let's say someone was
born with Huntington's and now they're in their twenties, like
you want to help them out and really, you know,
prevent them from how any problems in their thirties. I
think for a lot of diseases, one of the key
questions you have to answer is like when do you
have to intervene For some diseases, maybe it could be
(32:51):
very early in life. Maybe there's certain biological processes that
just take place early in life and you need to
do the edit before then, or else maybe you have
to come up with some other way of reversing the disease.
I think, fortunately for seems like maybe most diseases you
can edit an adulthood and that can actually have a
very material effect on the disease. But that isn't going
to necessarily always be true.
Speaker 1 (33:12):
Okay, got it. And so coming back to this conversation
about what society will become, it may be that some
of it is not an issue that you're born with
and you have to deal with, but that you make
a choice, just like anibolic steroids, that people are doing
it that way. Do you suppose that people are going
to be looking for things that involve longevity as one
(33:34):
of their first aims with this.
Speaker 2 (33:36):
Yeah, I mean, obviously there's a huge amount of interest
in longevity. I have a personal interest in living a
healthy life. For a long time anyway. I think I'm
definitely fall more on the spectrum of like health span
versus life span. If I'm living to be two hundred,
but i'm you know, de crefit and can't remember my kids,
that's not a life I personally wanted to live. But
if I live to a very healthy one hundred and
ten and where you know, I die in my sleep,
(33:58):
that sounds great to me. So I think longevity is
definitely an area where gene editing could play a huge
role in terms of you know, what are the processes
is like, you know, some sort of mutation accumulation in
certain areas that's like causing these cells to age in
the way they are, and could we reverse that with
genetic editing approaches. I think that is a very reasonable
(34:18):
and potentially promising line of research. I think that in general,
some of the biggest longevity things we can do though
today is like, you know, heart disease like cancer obviously
being a big one, and those are of course directly
addressable by genetic editing as well. And it goes to
interesting questions of like, should we edit millions of people
(34:39):
in the US to reduce their risk of heart disease
by thirty percent. That could say tons and tons of lives.
It's a relatively large in invention for them. So obviously
you'd have questions about safety. So far, crisper seems to
be very very safe at least based on the trials
and humans so far. So that's something we could do.
Is that something we want to do as a society?
Speaker 1 (34:58):
What would be the pros and cons?
Speaker 2 (35:00):
So the pro would be you reduce let's say hard
tech and it all cause mortality essentially and a huge
segment of the population. The con would be there's going
to be some expense associated with that. Do we want
to pay that expense as a society? Maybe it saves
us money in the long term because both people are
more productive and you're also spending less and kind of
in stage care in the hospital.
Speaker 1 (35:21):
And then see that as a government program that's paid
for as opposed to individuals saying, hey, I'm going to
pay for this.
Speaker 2 (35:26):
Well, I think that's a very interesting question as well,
and I think you could see stratification there of maybe
you know, frankly wealthier individuals choosing to get a lot
of these types of technologies, whereas you know, is that
available to everyone. That's the kind of choice for society.
And then of course the big one would be safety.
You only want to do that if it's extremely safe, right,
because you're trying to prevent disease kind of an aggregate,
(35:49):
so it needs to be extraordinarily safe for each individual.
Speaker 1 (36:10):
Do you think if you're interested in longevity, do you
think you're going to see this in your lifetime where
there are edits that can be made Let's say forty
years from now, where you say, hey, this is great,
I'm going to live longer. I'm going to expand this.
Speaker 2 (36:23):
Yeah, it's an interesting question. I wouldn't be surprised if
there's things that can maybe get you ten to twenty
percent further along. Are we going to see like a doubling.
I mean, that'd be great. Sure, I'm not going to
be root against it. I would be surprised. Frankly, we've
run a natural experiment. There's billions of humans on Earth
with all sorts of genomes. No one seems to live
(36:46):
over one hundred and ten hundred and twenty. Let's say
that doesn't mean you know, it's not possible, but I
think that one of the areas where I think we'll
see way more progress on is like health span within
that period. So like if you can live to an
extraordinarily healthy one hundred ten where you're hiking mountains and
you're having fun with your kids, that's already a huge
extension of that's like a twofold extension of life relative
(37:08):
to what a lot of people really kind of practically experience.
And I think glip ones and things like that, the
obesity drugs from the Lili and Novo and others, I
think that that's also kind of u shown that there
can be these kind of giant mass markets in biottech.
And longevity is the other one that everyone always kind
of thinks about, but there's others as well. You can
(37:30):
imagine things that mitigate like alcohol consumption or you know,
other areas. I don't I don't think glip ones are
going to be the only kind of trillion dollar drug
in biotech, but I think it's the first, and I
think hopefully that kind of inspires everyone else in biotech,
including us at Mammoth, to really think more broadly and
more fundamentally about, Okay, what are the things we can
do that actually change society for the better overall, not
(37:51):
just necessarily for specifical you got to start with specific
things and knock out rere diseases. But I think in
terms of like the long term vision of Mammoth, I
think that becomes very very exciting.
Speaker 1 (38:01):
And I've been throwing out numbers like three years, five years, ten,
But what you see, given your incredibly specific view on
what is happening right now, what you're capable of doing,
what is that time scale that we're talking about.
Speaker 2 (38:16):
Yeah, so I mean, going back to the beginning of
the conversation, Already, today people are being treated for sickle
cell disease using crispers.
Speaker 1 (38:24):
That's today.
Speaker 2 (38:25):
I think over the next five years, for the tissues
that are kind of most easily accessible, like blood and liver,
people are going to be shocked at how much progress
is made at curing rare diseases in those areas. And
these are kind of things where it's like it happens
slowly and then it happens all at once. It's very
much like that. And then I think over the next
ten years, you're gonna, because of you know, Mammoth, be
(38:49):
able to see us knocking out diseases and like muscle
and brain and all the other tissues of the body,
and I think it's going to take time, and there's
a lot.
Speaker 1 (38:58):
Of diseases to go through.
Speaker 2 (38:59):
But I think if we're sitting here a couple decades
from now and people are still suffering from rare disease,
we've done something incredibly wrong, Like things have gone off
the rail somewhere, and that's insane. Like to live in
a world where genetic disease is really a thing of
the past would be transformative for those patients, but also
I think for society generally. And I think once you've
(39:20):
done that, that's when you in parallel, because now you're
showing the safety, Now you're showing that this is an
effective technology. I think you can start to dream even bigger.
You can start to think about, like, you know, how
do you go after reducing cardiovascular risk, how do you
go after even more esoteric things like thinking about health span,
Like there's certain people that have short sleep and they
(39:41):
actually only need to sleep like three to four hours
a night, Like what if we could all do that?
Speaker 1 (39:45):
Right?
Speaker 2 (39:45):
Like just really thinking about how do we transform society
for the better and kind of more aggregate ways. That's
really long term where I get very excited.
Speaker 1 (39:55):
Unlike traditional medicine, which addresses symptoms of disease, gene editing
technology in general could change really fundamental aspects of who
we are. And so what do you think this does
to personal identity? Yeah?
Speaker 2 (40:09):
I think to your point, this is a very different
way of doing medicine. Like often medicine is treating symptoms,
often very effectively, but really treating symptoms, whereas this is
going into the core, into your DNA and really solving
the problem at it.
Speaker 1 (40:24):
Right, But I mean not just helping with disease, but
enhancing humans, changing who we are. So yeah, what does
that do to our sense of personal identity? Yeah?
Speaker 2 (40:33):
I think it's definitely something where we have a deep
kind of personal identity obviously in terms of how we think,
how we act, how we dress, and I think long term,
just truly thinking like one hundred years here, maybe we
start to think more of our genomes as our clothing, right,
Like we think of our clothing as representing our personal identity.
(40:54):
And that's fine, and that's something people embrace, and people
of all sorts of different styles and things they do.
But right now, that's not very much how we think
of our genomes. But if genomes become malleable, and they
become something where you really do have this option of
kind of choosing what things you want to keep or change.
Maybe we start to see that more as kind of
extension of ourselves. That's not core in the sense of
(41:17):
it can never change, but core in the sense of
I want that to reflect who I am as an individual,
and I have the choice of how that looks.
Speaker 1 (41:23):
Oh, that's great. Yeah, in the same way that someone
might go off and get blonde hair for a while
and red hair and dark hair and change color their
eyes or whatever. There are ways of doing the stuff now,
and there's can be better ways or more direct ways
of doing it. What do you suppose that means in
terms of motivation and earning something like, for example, I
go to the gym and I lift weights. It's really hard.
But if I could go and.
Speaker 2 (41:44):
Sure you get your miostatin gene blasted and you just
have a huge muscles from setting home on the couch.
I think that's an interesting question at the society level,
because why do we care about muscles? Why do we
care about other things? Like at other times in society,
having pale skin has been something that people value. I
mean still today in many places, and it's because oh,
you don't have to go work in the farms, and
(42:04):
that means you're a high class individual with a lot
of money. Or in some societies even today and in
the past, being very overweight was a sign of high
status because you're not starving. And I think that what
that could mean, and this is just like you know,
purely hypothesizing, is maybe being healthy remains an important thing,
(42:25):
but it's not a reflector of status in the same
way it is today, which would be awesome, Like what
if actually everyone is walking around super healthy, Yeah, amazing,
But maybe that means that there's less of a status
differentiator of oh, this person has time to go to
the gym and they work very hard, so something else.
But you're humans, right, we love Frankly, it seems to
stratify ourselves based on status. So some new thing will
(42:47):
come up and it'll be like, oh, they have a
blue hat. That's the sign of, you know, high status,
and we could pass the judgment on whether that's good
or bad. But I think that's probably what would happen,
is that it just means that a society is better
off overall because everyone's very healthy and has the right
amount of muscle, but there's a different status game being
played in terms of you know, when you go to
the club on a Friday or whatever.
Speaker 1 (43:13):
That was Trevor Martin, co founder and CEO of Mammoth Biosciences,
We talked about the emerging tools that allow us to
edit life at its most fundamental level, the conversation and
the tools he's building. This allows us to look at
the near future in which we can slice out chunks
of the genome, or rewrite individual letters, or even fine
(43:37):
tune the expression of genes without altering the sequence. And
eventually this gives us finer and finer control over our
biological destiny in ways that we're only beginning to understand.
Because these technologies are not going to only give us
the chance to fix mutations, They're going to expand what
(43:58):
is possible. They will read find the relationship between who
we are and who we might become. Where we stand
now is in a field of question marks that no
single thinker can answer alone. Questions about the line between
therapy and enhancement, between responsibility and hubris, between embracing the
(44:21):
malleability of life and respecting everything. We don't understand about it,
Only one thing seems certain. At this point, we are
no longer just passengers on evolution's very long and winding road.
We are taking the wheel, and with that power comes
a great responsibility, the weight of choices that are going
(44:43):
to ripple through generations, the weight of choices that will
shape the genetic landscape of those who come after us.
In the end, our role is going to be to
learn how to annotate the book of life with great care,
to correct its most tragic errors while preserving the poetry
(45:03):
of its imperfections. We now see the genome not as
a finished book, but instead as a draft in progress,
and that compels us to constantly ask ourselves, how much
of the story should we change? What kind of story
do we want to tell? And how can we be
the most careful custodians of the possibilities. Go to Eagleman
(45:31):
dot com slash podcast for more information and to find
further reading. Send me an email at podcast at eagleman
dot com with questions or discussion, and check out and
subscribe to Inner Cosmos on YouTube for videos of each
episode and to leave comments. Until next time. I'm David Eagleman,
and this is Inner Cosmos.
Host
David Eagleman
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