September 23, 2026 • 39 mins
What if the computers of the future are alive? Scientists are growing tiny clusters of human cells called brain organoids, connecting them to electrodes, and training them to perform basic computing tasks. Does anyone remember Pong?
Journalist and musician Claire L. Evans joins Oz to take us inside her reporting on the emerging field of “organoid intelligence.” They discuss whether living cells could one day rival silicon, what organoids could teach us about the human brain, and the thorny ethical questions scientists may need to address in the near future.
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Speaker 1 (00:16):
Welcome to Tech Stuff. I'm Oz Veloshian. There's only one
way to put this. I read one of the craziest
articles in recent memory, recently in Wired. It's called AI
is Dead, Organoids are Alive. And it's a look inside scientists'
attempt to grow computers powered by human cells grown in
a lab. Written by Claire L. Evans, a journalist, a
(00:37):
speculative fiction writer, and a musician with the band Yacht.
who also had some remarkable experiences reporting this piece that
she's here to share with us today. Claire, thank you
for joining.
Speaker 2 (00:47):
Oh, thank you so much for having me.
Speaker 1 (00:49):
So talk about organoids and this quote that you have
early in the piece, I'm going to let you in
on a secret. Every cell in your body has the
potential to get smarter.
Speaker 2 (01:00):
Yes, that's technically true. You can take any cell from
the human body, normally skin cells, but also hair, follicle cells, teeth, blood,
these all work. You can introduce those cells to a
special cocktail of proteins. Those cells will revert to their
embryonic state. They will become stem cells. They will become pluripotent,
(01:20):
which means capable of turning into many other different types
of cells. And you can turn those cells into neurons
and from there build all kinds of interesting things.
Speaker 1 (01:30):
So what is an organoid?
Speaker 2 (01:33):
Okay, well, big picture. An organoid is... essentially a small
spherical glob of human cells that reproduces on some different levels, structural, molecular,
developmental levels, some aspect of the body part from which
those cells were drawn. So you can think of it
as like a mini model of a human organ made
from the cells that constitute that organ. You can make
(01:55):
stomach organoids, for example. You can make cardiac organoids. You
can make tear gland organoids, and you can make brain organoids.
Speaker 1 (02:03):
The brain ones are the most fascinating ones, right?
Speaker 2 (02:05):
The brain ones are very interesting, but let us not
forget the others.
Speaker 1 (02:08):
We need all the organs.
Speaker 2 (02:12):
We need all the organs and it's fascinating. I mean,
heart organoids will beat, you know, tear gland organoids will
cry and brain organoids will, I mean, I wouldn't say
they think, but they definitely create synaptic connections. They crackle
with all kinds of electrical activity. They form these basic
structures that are similar to like a fetal brain. They
do brain things just on a much, much smaller scale.
Speaker 1 (02:34):
But you can take a skin cell and turn it
into a brain organoid?
Speaker 2 (02:37):
You can take a skin cell and turn it into
a neuron and then put enough of those neurons together
in a little dish, keep them warm and happy and well-fed,
and they will do what cells do, which is just divide, multiply, cohere, aggregate,
and form these little structures. There's an upper ceiling on
how big they can get because they don't have vascular system.
They don't have veins. to kind of cycle nutrients in
and clear out toxins. So they can only grow to
(02:59):
about five millimeters in size before they develop what's called
a necrotic core and suffocate from the inside out. But
within that tiny scale, you can have like five million neurons.
And that's about the size of a bee's brain. So
you can do lots of really interesting neuroscience research and
pharmaceutical testing with just that.
Speaker 1 (03:17):
What got you onto this story?
Speaker 2 (03:19):
Oh, there was a big splashy, I mean, I'm following,
you know, all the publications within this sort of space
of the overlap of computation and biology. It's my beat.
I'm very interested in those places where technology touches life
and vice versa. I think that's where technology is headed
because I believe that there is a limit to what
we can do with silicon. And I think there's also
a limit to how much silicon there is left in
(03:42):
the world to build things with. I mean, We're literally
running out of sand. We're running out of minerals. These
things are not renewable. So I'm really interested in where
biology can come in and provide alternative ways of not
just thinking about technology, but also alternative substrates and ways
of building technology that is more resilient, more efficient, more
in line with how the world already works rather than
(04:02):
the sort of artificial construction we call computing. Anyway, that's
neither here nor there. I have been following this intersection
for a long time, and there was a big splashy
press push out of Johns Hopkins University a year and
a half ago, pushing forward this idea of what they
were calling organoid intelligence. So organoids have been around since
like the early 2000, 2008, 2009. And they've been a
(04:23):
staple of basic research. But all of a sudden, there
was this outpouring of research around like, how can we
connect these organoids to computer systems and do computer things
with them? And they were calling it organoid intelligence. They
were trying to make a big swing to kind of
name this field and bring a lot of talent to it. Yeah, OI.
Speaker 3 (04:40):
OI.
Speaker 2 (04:40):
So I was like, this is something interesting. I don't
know how much of this is hype, how much of
this is just scientists trying to get press and funding
by sucking on to the hype around AI, or how
much of it is actually really going to transform how
we think about computing. And that's, yeah, it just nagged
at me for a long time until I finally got
approval from my editors to go figure it out.
Speaker 1 (05:00):
How are they actually used today? I mean, how much
of this is about the future where groups of brain
organoids can replace silicon-based chips to do computing, and how
much of it is more like these have a purpose
for drug testing or for other types of laboratory experiments?
What is the actual use case today, and where's it going?
Speaker 2 (05:20):
Well, obviously, we're a very long way away from living
AI systems. And, you know, there's like in all kind
of biology and basic research, not an enormous amount of
funding in this space compared to the kinds of resources
that are being put towards silicon-based intelligence. But we are
making quite significant strides. So, I mean, currently the state
(05:41):
of the art is we can grow brain organoids very
consistently at scale. We can grow them directly onto microelectrode arrays.
I say we, I mean like humanity. Obviously, I'm not
doing this. Onto these kind of electrode arrays, and then
we can stimulate them with electricity because very conveniently the
human brain responds to electricity as do conventional computing components.
(06:02):
So we can stimulate these neurons and then they will
sort of respond in kind and we can measure those
responses and in that process develop a kind of rudimentary
form of programming. So there are a number of researchers
who are training neural systems, both three-dimensional organoids but also
flat two-dimensional neural cultures, to do basic tasks that would
(06:23):
normally be done by AI, things like image classification, text recognition.
There's a very splashy.
Speaker 1 (06:29):
But that's not happening today already, right? Yeah, yeah, that's
totally doable.
Speaker 2 (06:32):
It's just, it's inconsistent and slow.
Speaker 1 (06:34):
Right.
Speaker 2 (06:36):
But it is absolutely possible.
Speaker 3 (06:37):
Wow.
Speaker 2 (06:38):
Yeah. I mean, obviously, it's not like neurons are using
their eyeballs to look at pictures of text and saying this, this,
or this, but the text is being translated into electrical
signals and then fed to those organoids. The organoids are
responding in kind and translated back. So there's a movement
between analog and digital that happens, you know, with all biological... interfaces.
You have to move from our world of bits and
(06:59):
bytes to their world of biochemistry and electricity and back again.
But we're figuring out how to do that. So it
is possible to do that. There is a startup in Australia.
Speaker 1 (07:08):
I like that you described our world from the point
of view of being a computer and their world from
the point of view of being an organoid.
Speaker 2 (07:14):
Yeah, I mean, the thing that I.
Speaker 1 (07:15):
They inverted us and them, human-machine paradox.
Speaker 2 (07:18):
I know. Honestly, it's so disorienting thinking about this stuff because...
Our cells make us, right? I mean, we're all made
of millions and billions of cells, but also they are
perfectly happy living without us. You can take these neural cultures,
put them in a dish. If you keep them fed
and warm, they will just live essentially forever without any
(07:39):
intervention from us. Like if you make an organoid out
of your own skin, is it you or is it
not you anymore? There's this sort of autonomy that cells have.
And when you sort of separate them from the human
system and let them do their own thing, they have
their own kind of onboard capacities that are unrelated to
the organism they form at scale. It's kind of disorienting
(08:01):
ontologically and bizarre.
Speaker 1 (08:03):
You had this great quote, brain organoids are creepy. They
muddy the line between person and thing, which is like
the difference between humans and animals or the living and
the dead. It's a fundamental distinction. The trend turns culture.
I thought it was a really fascinating way of putting it.
Speaker 3 (08:15):
Yeah, yeah.
Speaker 2 (08:16):
That's something that came from some sociological research on kind
of the way people respond to organoids. An interesting, I think,
actually consequence of this piece is when I was writing it,
I was talking to a lot of sociologists of science
and bioethicists who were really invested in the question of
brain organoids. And they all kind of more or less
told me, yeah, people don't think brain organoids are weird.
(08:37):
people understand that it's for the greater good. It's for science.
They're not unsettling. They're not eerie. They're not that strange.
There's not going to be a lot of pushback against
this technology when it makes the leap to computing because
people kind of understand biomedical research. Everybody was very confident
in that. And then I published this piece and the
response has been across the board, people being like, ah,
(08:58):
you know, freaking out and being kind of horrified on
some fundamental level about the idea of a computer having
some living cells in it, I think people find it
much more morally objectionable than I think the bioethicists would
be comfortable to admit. So that's been an interesting consequence.
Speaker 1 (09:17):
Are they just small human brains?
Speaker 2 (09:20):
Well, if you talk to anyone in this space and
you call these things mini brains, they get really touchy.
They go, these aren't mini brains. These aren't mini brains.
These aren't even brains. I mean, a human brain has
171 billion cells, including both neurons and glial cells, which
are kind of the scaffolding. An organoid has maybe five million.
There's an enormous difference in scale. And what makes a
(09:43):
brain a brain is, I mean, a subject of ongoing debate, obviously. But,
you know, there is the general consensus that some emerging
capacity comes at this scale that is maybe not legible
at such a small scale. There's also long been this
sort of ambivalence, I guess, or even like outright distaste
(10:04):
on the part of the scientific community for talking about
questions of consciousness or sentience or even really intelligence.
Speaker 1 (10:11):
Not from the AI community.
Speaker 2 (10:13):
Well, the AI community is all for it. They think
they're so ready to ascribe sentience to absolutely anything. you know,
put a couple googly eyes on a laptop and all
of a sudden it's a person.
Speaker 1 (10:21):
Let me ask you about the headline of the piece,
AI is dead, organoids are alive. I mean, I guess
your editor chose the headline, but is that, what are
your thoughts on it?
Speaker 2 (10:31):
I mean, I think there is something really interesting about
the way that neurons process information that silicon systems will
never be able to achieve. I mean, neurons have the
capacity to grow and prune their synapses based on their
experience of the world. I mean, In the case of
an organoid, that experience is electrical signals or maybe some
(10:52):
chemical stimulus in a dish. It's not the same thing
that we think of as experience at the human scale.
But it is like an embodied experience, an embedded experience
of the world. And some philosophers call that nano-intentionality. It's
essentially the idea that living matter can respond to its
environment in real time. and yeah i mean ai systems
(11:15):
even the most sophisticated ai systems they're still built on
these sort of static elements which are not you know
self-assembling they're not responsive to the world they're not uh embodied.
Speaker 1 (11:25):
The chips aren't but the models are.
Speaker 2 (11:27):
No yeah i suppose so i mean i just think
there's like a i don't know there's just like a
sort of fundamental i guess sort of philosophical distinction between
these substrates whether you want to call that dead versus
alive i mean that's an editorial choice but I mean,
I do think the comparison between, you know, rocks and cells,
because I mean, computers are just rocks, right? And cells
(11:50):
is an instructive one.
Speaker 1 (11:52):
Talk about the experience of actually reporting the piece. I
want to know about your trip to the UC San
Diego Stem Cell Institute.
Speaker 2 (12:01):
Yes. So I had a great fun reporting this piece,
although I will tell you that like all cell culture
labs pretty much look the same. You know, they're not
like full of like bubbling beakers and brains and jars
like you would imagine. You know, it's incubators that basically
look like mini fridges with trays and trays and trays
of these like nutrient wells that basically look like contact
lens solution and little globs floating in them. Those are
(12:24):
the organoids. You know, it's not hugely glamorous. At UCSD,
they do have some robots. So there are people there
who are working on organoid controlled robots, which is quite interesting.
Speaker 3 (12:34):
Wow.
Speaker 2 (12:35):
They're doing a lot of really kind of strange and
interesting work. They're, for example, creating genetically modified Neanderthal brain
organoids to understand the difference between human and Neanderthal brains.
Speaker 1 (12:45):
Whoa.
Speaker 2 (12:46):
How do they do that? I'm not entirely sure, to
be honest with you.
Speaker 1 (12:49):
Are they from fossils? Are they sequenced DNA?
Speaker 2 (12:52):
Yeah, I think they are just... you know what i
don't know i don't know 100 no but there's an
entire neanderthal organoid department within.
Speaker 1 (12:59):
The ucsd stem cell research crazy.
Speaker 2 (13:02):
Yeah they're also sending organoids to space to understand how
like radiation affects human astronaut brains i mean the thing
is that you know organoids provide a basis for studying
the brain in so many different ways i mean the
obviously the ai stuff is splashy and exciting and we
love robots and we love computers but We know very
little about how the human brain is even formed in utero.
(13:25):
Because of ethical guidelines on research, we don't really know
what happens after about 14 days. Between 14 days and
nine months, we have no idea how the human brain
comes together. Everything we know about it, we've learned from
analogy through studies of rats and fruit flies and stuff.
So an organoid, which is essentially like a fetal mini, mini,
mini brain, allows researchers to understand basic things about human
(13:47):
brain development. And that's a lot of what's being done
in that particular lab. It's like the study of human
brain development. And the AI organoid piece is just one
other way of getting at those questions. Because if you
can train, quote unquote, you know, a wired up organoid
to respond to certain electrical stimulus, to perform certain tasks,
(14:08):
for example, playing a simple video game, then you can,
you know, expose that organoid to different environmental factors, to
different toxins, to different pharmaceuticals. and understand how those things
affect that little nascent brain's capacity to respond to those tasks.
So it's another piece of a toolkit for understanding how
(14:28):
the brain works.
Speaker 1 (14:30):
So who is Alison Mowatry?
Speaker 2 (14:32):
Alison Mowatry? Alison Mowatry, yeah. He's a developmental biologist at UCSD.
He's a leading organoid researcher. He's part of the sort
of larger organoid intelligence effort or cohort, but he's fundamentally
more interested in things like autism, human brain development.
Speaker 1 (14:49):
His son is autistic, right?
Speaker 2 (14:51):
Yeah, his son is autistic. And he actually has created
organoids from his son's cells in order to understand how
his son's brain works, which is really fascinating to me.
And I asked him, is it weird to you to
be looking down a microscope at a miniature brain made
out of your own son? And he told me that
(15:12):
he has to kind of just disassociate in order to
do the research and not get too emotionally invested in it.
Speaker 1 (15:19):
How did actually going to labs change your understanding of
the story?
Speaker 2 (15:22):
I think the most beneficial thing for me about going
to a lab is actually being able to sit down
and talk to scientists face to face and get a
sense of their vibe. Because, I mean, I don't have
a background in neuroscience or computer science for that matter.
So there's only so much I can really get out
of reading academic papers. I mean, I try my darndest,
but at the end of the day, going up to
(15:43):
the scientists and saying, how exactly did you do this
and what does it mean? I mean, of course, I
ask all the important questions like, what happens if you
eat an organoid? And I think it was Alison Mowtri
who told me that nothing happens if you eat an organoid.
You'll just digest it. But if you are working in
a lab with an organoid that was made from your
own cells... That's extremely dangerous because if you get any
(16:06):
part of that organoid back in your body by accident,
your bloodstream, for example, through a cut or a lesion
of some kind, it will reenter your body, having developed
outside of your body, and it will start dividing and
multiplying and it could cause cancer because that's essentially what
cancer is, is cells going rogue and dividing and multiplying
outside of the multicellular project of the body. So it
(16:28):
will have become independent, returned within... And gone rogue, which
I think is just absolutely fascinating and strange. But yeah,
I mean, my favorite thing about this kind of research
is just going into labs and asking the wackiest questions
I could possibly think of to sort of throw these
people off balance. And also, you get really fascinating answers. That,
to me, is such a strange reality of cellular research.
(16:52):
You can't work with your own cells because they might
infect you.
Speaker 1 (16:55):
Is mortuary making progress on the autism question?
Speaker 2 (17:00):
Yeah, I think so. I mean, I think he's studying
how the development of an autistic organoid differs from a
neurotypical organoid. Obviously, it's a really complicated thing to entangle.
But yeah, I think he's definitely making progress, looking at
different kinds of therapies that might emerge from this. And
he seems very optimistic that he can make a real difference.
Speaker 1 (17:19):
Who told you that you don't need permission to torture
as many flies as you want? And what does that mean?
Speaker 2 (17:26):
That was this amazing sociologist, John Evans, who's also at UCSD.
who has made a career of like kind of being
a sociologist of biology and bioethics. So he was a
great outside observer to talk to about this stuff. Yeah.
What he was saying was basically that the regulation around
experimenting with this stuff is a little bit, it's a
little bit unclear. Like there are very specific roles about
(17:47):
working with different kinds of animal models, right? Like if
you're going to do experiments on rats or apes, like
you have to go through all these different, you know,
reporting guidelines and ethical guidelines and You know, there are
ways that you appropriately euthanize an animal after you work
with them, things like that. There's no such regulations in
place for organoids. They're kind of equivalent to working with invertebrates,
which is also kind of unregulated. I mean, that's changing
(18:10):
a little bit now because there's new research about like
pain reception and sentience in insects. But from a legal standpoint,
you don't need to get permission to, you know, torture
as many fruit flies as you want. That's why fruit
flies are very common. in biology labs. And it's the
same thing for organides right now. You don't necessarily need
legal approval. It's not understood that they feel pain, for example.
(18:33):
So there's no real concerns around that for now. But
these organides are getting more and more complex. And now
that we're connecting them to these electrode arrays and stimulating them,
you could make an argument that they're having experiences, which
has an effect on how we think about sentience and consciousness.
I mean, there are philosophers of mind who think that
(18:54):
these things sentience and consciousness are a consequence of experience,
of an embodied experience of the world. It's also possible
now to create what are called assembloids, which is where
you take organoid structures from different parts of the body
and kind of glob them together. So you can make
an organoid that can see, for example, or at least,
you know, perceive light. So there's different sort of forms
(19:14):
of input now that we can create. And those, I
think it's getting more and more kind of morally, or
not morally, but ethically gray. in terms of what we
feel is permissible to do with these little human-not-human cellular structures.
Speaker 3 (19:28):
Can they learn, and what does it mean when they learn?
Speaker 1 (19:47):
Can they learn? And what does it mean when they learn?
Speaker 2 (19:50):
Yeah, they can learn for sure. You can kind of
train them. So actually the best, I think, research in
this comes out of this biocomputing startup in Melbourne called
Cortical Labs, who basically did a series of experiments that
have served as a proof of concept for how one
can program these systems. There's a theory in neuroscience called
the free energy principle. It's way above my pay grade,
(20:13):
but I can try in the simplest of terms. It's
essentially just the idea that self-organizing biological systems like predictable stimulus,
they will rearrange themselves to avoid chaos because that way
it is easier to anticipate and predict change. It takes
more energy to respond to a radically changed environment than
(20:34):
it does to one that is regularly stimulating. And so
you can essentially subject, expose neural cultures to chaotic stimulus
and they will do everything they can to avoid that.
So If you pair regularly spaced signals with an input
that you want, like for example, in the case of
this research, it was to play the video game Pong.
(20:57):
So if the electrical signals representing the ball hitting the
paddle are associated with some like regularly pulsing input, the
neurons will rearrange themselves in order to create that outcome
as much as possible. So you essentially reward them with
regular electrical stimulation. It's hard to say, like, do they
like that? Is it something that they enjoy? You know,
(21:20):
these kinds of words are ambiguous at best, but they
will certainly rearrange themselves to create those conditions. So that's
a kind of a proof of concept for this neuroscience theory.
It's also has proven to be a useful way of programming.
I'm told there are other ways that are being developed,
but it's really like very early days. And there are
a number of different companies now who are creating these
(21:42):
kind of networked organoid systems. So they have cultures of
organoids kept alive in these, you know, little kind of
biological computers. Those biological computers are connected to the internet,
you know, a neural server, if you will, which sounds
very sci-fi, but essentially what it means is that it
allows people who are wanting to work with organoids in
this capacity to do it remotely. It's kind of like
(22:04):
actually quite analogous to like the early days of, you know,
the internet when researchers wanted to access resources at computers
and different sites on the ARPANET, they would do that
remotely rather than having to like travel there and do it.
So There are now ways of remotely programming these systems
and studying their responses in all kinds of different ways.
So there's lots of different research being done all over
the world on these networked neural servers to essentially articulate
(22:29):
what the programming language of biology will be. And it's
as yet unknown. I mean, electrical signaling is definitely the
most efficient way, but there's also an enormous amount of
neurotransmitter chemicals in the human brain that neurons use to
communicate with each other. It's possible that we might be
able to do so chemically. That's a little bit slower
and more diffuse, but there could be applications for that
(22:50):
as well.
Speaker 1 (22:51):
And you did this, right? I mean, you interacted with
organoids over the internet.
Speaker 2 (22:56):
Yeah, I played Pong with some neural cultures online. I know,
it's pretty wild. I mean, I needed to be walked
through it by, you know, an engineer at this company
because these neural cultures are addressable in Python. So there
is some programming. It's not like you're just playing online,
you know, as you would like any kind of online game.
But yeah, you run them through these trials repeatedly and
(23:16):
over time they get better and better at hitting the
paddle back and rallying. And over time, yeah, they improve.
They're not very good at it. They're still not very
good at it. And they can play Doom now. That
was like a big viral news story some months ago.
Similar technique, just more complex input. They're also not very
good at that either, but they can do it. And
(23:39):
that's really like a starting point.
Speaker 1 (23:41):
Was it uncanny for you? Or was it like you're
in a Waymo and it's sort of uncanny for the
first 20 seconds and then you go back on your phone?
What was the personal experience for you of interacting with
these organoids?
Speaker 2 (23:53):
It's very surreal because I just felt this weird burden
of responsibility. I mean, I had access to this beta
server system where you could control all the environmental factors.
You could control the CO2 balance and the temperature of
the server in which the neurons were being held. And
I was highly conscious of the fact that if I
just like clicked in the wrong place, I might kill them.
(24:15):
And that is something that, I mean, I say this
in the piece, but it's, that's a new paradigm in computing.
Like you don't normally expect when you do something wrong
on a computer that something dies as a consequence of
that error. And I don't know, I felt very, I was,
I was treading very carefully. I felt like a bull
in a China shop. You know, I was like, I just,
(24:36):
I want to make sure these organoids stay safe and
happy in their little in their little petri dish in
australia yeah strange it's a it's a strange feeling to
interact with something alive online i mean i suppose it's
not the first time i suppose like webcams of nature
you know you have like these portals into the living
world but so rarely do you have the capacity to
actually physically interact with something that is if not sentient
(24:59):
then alive.
Speaker 1 (25:01):
Is the melbourne is that where cl1 is yes yes
and one of the creators of CL1 said CL1 is
the theoretical neuroscience as the Large Hadron Collider was the
theoretical physics. What does that mean?
Speaker 2 (25:16):
Yeah, I mean, that's kind of that thing I was
talking about earlier about how they figured out a way
to program these neurons based on the theory of the
free energy principle, which is this neuroscience theory that they
essentially tested in silico, in utero in silico. I don't
even really know how you would describe what it is.
But I mean, yeah, they were able to kind of
(25:37):
take an idea from theoretical neuroscience, translate it into a
series of commands, interact directly with the living system, and
then see that that theory was in fact true. So
that was a way of using the CL1 to test
basic neuroscience theories, which is really, I think, exciting for
a lot of people. It's a little bit grand of
a claim, of course, but I don't think it's incorrect.
(26:00):
These are self-contained systems for testing theories of mind. It's
truly wild. And it's so interesting to talk to these
people because they have actually like a, you know, I
think some of the response to the Wired piece from
the general readership was kind of like, this is unholy.
These people have no respect for life. You know, there's
a sacred spark in the human mind and we are
(26:23):
befouling it by putting it in computers and instrumentalizing it
or objectifying it. And I think all of that is
absolutely valid and based on the track record of biomedical
industry and the tech industry a very fair assessment. But
I did find that talking to these people, they're all
incredibly sincere about wanting to understand how intelligence works, wanting
(26:46):
to understand the secrets of biology in a kind of
synthetic and constructive manner. I think the history of biology
has been, it's a very reductive science. Scientists have tried
to like understand all the little tiny pieces and how
they fit together. There's been this belief for a long
time that if we could just look in a microscope
small enough, we'll see how it all works. And at
(27:09):
the end of the day, there's certain things you can
only understand through building. You can only understand in a
kind of synthetic way. And in a way, I think
these people are putting together these systems and they're developing
a knowledge of fundamental underlying structure of intelligence that they
could only really get by doing what it is that
they're doing. Now, what comes next, you know, 10 years
(27:31):
from now, 20 years from now, how comfortable we may
be or not be with living systems? Those are other questions.
But right now, at least, I feel like a lot
of the stuff is just driven by a genuine desire
to understand intelligence and a genuine respect for the complexity
of biological intelligence. I mean, a lot of these people,
they're building these hybrid computational living systems, but they know
(27:53):
that AI, as it's currently instantiated, is fairly limited. It's
trying to emulate something that is so much more complex
than most engineers are willing to acknowledge. And only by
starting to kind of work with those living materials are
they really coming to understand just how much biology is
(28:15):
doing that we aren't even conscious of or capturing or
even close to modeling in synthetic systems.
Speaker 1 (28:23):
But is the Holy Grail to replace silicon computing with
neural computing or organoid-based computing because it's so much more
energy efficient? Or is the holy grail to actually truly
understand how the human brain works?
Speaker 2 (28:39):
Can't it be both? No, I don't know. I mean,
I think different people have different intentions. And that was
something that was really clarifying about reporting the piece is that,
you know, I talked to a lot of different scientists.
Some of them, you know, they're interested in this stuff
because they want to understand how the brain works, how
the brain is formed. Others want the stuff to work
so that they can do more accurate Alzheimer's research or
(29:01):
test pharmaceuticals. Some of them are interested in the computational questions.
I mean, there's a wide kind of gamut of approaches.
But I do think that's all kind of grounded in
a healthy respect for the complexity of life. For some,
I think, yes, the end goal is to create AI
systems with living materials that are competitive with AI systems
(29:23):
made from silicon. I think everyone is conscious that that's
a very, very long way away. And in a way,
sometimes the more we learn about biology, the more we
realize that we have yet to learn. So I think
they're all humbled by that. But the hope is perhaps that, yeah,
both those things can be true that we can build
computer systems and in the process learn a lot about
(29:43):
how intelligence works.
Speaker 1 (29:46):
Can you kind of help me understand the difference between
what the researchers hope will eventually happen and what's actually
been demonstrated with organoids to date.
Speaker 2 (29:57):
Yes. Well, I mean, to be fair, I think a
lot of the researchers are pretty measured in their estimations.
And in my experience of talking to biologists is that
they're really any scientists is that they're quite reticent to
be speculative about these things. I mean, they have ideas
about what questions would be cool to ask and what
things they think are going to get them funding. But
none of them is walking around saying, like, in the future,
(30:17):
computers are going to be made out of brains and
it's going to be impossible to tell the difference between
computers and people or whatever. Nobody's making those claims. they're
making much more prescribed and limited claims. So there's not
an enormous gap, frankly. I mean, they're interested in, yeah,
being able to use these computing organoid systems to ask
more pointed questions within their own realms of research, if
(30:42):
that makes sense. But I think all the grand claims
come from, you know, the university PR departments and the
journalists and the people like us who want to kind
of look at this stuff and go, oh, this is
where it's headed rather than kind of sit with the
complexity of where it is.
Speaker 1 (30:59):
And one of the biggest obstacles is blood.
Speaker 3 (31:01):
Yes.
Speaker 2 (31:02):
Blood is really important. Vascularization is really important. There's an
upper ceiling for how big an organoid can get because
they don't have circulatory systems. They don't have veins. They
have no way of filtering out toxins and bringing in nutrients.
So there's some like Preliminary research being done now in
kind of artificial perfusion systems, you know, building these like
(31:23):
tiny microfluidic networks to kind of circulate nutrients throughout the
inside of the organoid. There are people who are building
vascular organoids, so like making organoids from like vein cells
to create these kind of rudimentary vascular structures. So we'll
probably break past that threshold in some way or another soon.
But for the time being... Yeah, they die after a
(31:46):
certain size because the cells on the inside of the
organoid suffocate without access to nutrients.
Speaker 1 (31:53):
And what are the other big obstacles?
Speaker 2 (31:56):
Funding, always, especially in the US.
Speaker 1 (32:00):
So there hasn't been a rush of capital around the
AI stuff that's also funded a lot of this?
Speaker 2 (32:05):
I didn't get the impression that there has been, no.
I mean, there are some startups in this space. there's
this company in Australia, there's a company in Switzerland that's
doing this. I think they are relatively well capitalized, but
not on the scale of like literally any AI company. Funding,
you know, within the kind of biomedical research context, basic
(32:26):
research is a real struggle right now in the US, obviously.
There is, however, like a turn towards organoid-based research in
the US because of a movement away from animal research models.
So the NIH just like basically said that it wouldn't
approve any grants that didn't include a like organoid type
(32:47):
system wow.
Speaker 1 (32:48):
It's a big stimulus yeah because there's.
Speaker 2 (32:51):
Just been this general kind of political and sociocultural move
away from animal testing which i mean organoids are great
in that regard because you know most especially like neurochemical
drugs uh psychiatric drugs fail in human trials because they're
tested on rats and you know rats don't get depressed
as far as we know so there is a limit
(33:12):
to what we can learn from animal models. And organoids
tend to be like a lot more representative chemically and
molecularly of what's happening in the human brain. So that's
a good thing. But yeah, I mean, funding is always
a constraint. I think, you know, the ethical questions are constraining.
I think for like basic organoid research, not so much,
but for this kind of computational stuff, I think there
(33:34):
is a lot of trepidation A lot of the, like
the Johns Hopkins team, for example, works with embedded ethicists
and is always touting the fact that they work with
embedded ethicists because I think they're sensitive to the fact
that people might get kind of squicked out by this
stuff and that could imperil their position. And so they
take everything really incrementally and, you know, they have regular
(33:56):
meetings between the people who are working in the wet
labs and the people who have, you know, who are
asking these kind of ethical sociological questions. They're very earnest
about that. It seems that they very much enjoy these
conversations and have this kind of constructive way of approaching it.
That being said, I mean, the bioethicists, you know, they're
embedded within these same biomedical institutions. So they might not
(34:19):
have the most clear outside perspective on how people in
the real world are going to respond to these things.
So that's a limitation for sure.
Speaker 3 (34:25):
Yeah.
Speaker 2 (34:28):
Those are the major ones, I would say.
Speaker 1 (34:30):
Just before we wrap, can you quickly explain the nature
of consciousness and how... i have to ask you the
consciousness question yeah.
Speaker 2 (34:41):
I mean the consciousness question is the question right and
it's one that absolutely none of the scientists want to
talk about i mean every single scientist i asked it's
like i was very careful to ask that question last
after i had proved my competency and all the kind
of bio biomedical aspects of this because they really don't
like talking about it not because they're not interested or
they don't like believe it's important because i think it's
all anyone ever asked them about you know and i
(35:02):
think they have a very different understanding of what consciousness is.
They're much more reluctant to label anything as being conscious
because they, I don't know, I think they work with
living matter all the time. They work with cells all
the time. They know what cells can do and can't do.
They're not precious about it. But yeah, I think the
(35:24):
question is they're, you know, somewhere between 5 million cells
and 170 billion cells, like something happens, right? Something called
consciousness dies. emerges. Whether that's possible in a dish alone
without external stimulus from the world, without an embodied experience
of the world, without parents or an upbringing or relation
with other animals and people and sensory experience, whether that's
(35:48):
possible in isolation is like an open question in philosophy
and in biology. Nobody really knows. I think a lot
of the reluctance that I encountered with talking to biologists
about this question is that there's no like quantifiable definition
of consciousness. You know, it's something we've been debating since
ancient times and nobody really knows how to name it.
(36:12):
And that makes it really difficult to say whether something
is conscious or not conscious. I mean, for example, an
organoid is about the size of a bee's brain. Do
you think of a bee as a sentient organism, a
conscious organism? Even within science, there's a huge gamma of
responses to that question. I personally would think a bee
is sentient. but others might not. So where we draw
(36:34):
those lines is ultimately quite personal and socially prescribed and philosophical,
and it's going to make it really difficult to guide
this research ethically. I mean, I think everybody's keen to
err on the side of caution with this stuff, but
it does feel inevitable that at some point along the road,
(36:55):
as these things get older, more mature, more complex, As
we start stimulating them and giving them sensory experience, some
thresholds will be crossed. And in the absence of any
way to infer conscious experience from the outside, we have
to be very careful. For the time being, I don't know.
(37:18):
I really don't know. It does seem to me, though,
that when you are giving these cells experience, you're putting
them well on the path towards something like consciousness even
if it's like a micro shade of that it's got
to be a piece of that puzzle and.
Speaker 1 (37:37):
One of the most fascinating things in your piece i
think is that these organoids and cells their primary motivation
is to connect apparently.
Speaker 2 (37:47):
Yeah yeah well neurons that's what they do right they
forge connections with each other every neuron has many many
connections with every other neuron it's it's their cellular imperative
so you put them together That's what they do. They
form these kinds of aggregations in the absence of a body,
in the absence of a brain, they'll still do what
(38:08):
they do. And I find that really beautiful. Like the
fact that all of our cells have these, I mean,
this is kind of like loaded language, but have these drives,
have these capacities, I guess, that kind of don't even
require us to be there in order to transpire. They
just do what they do. They're unfailingly resilient in that way.
And that's why life has been so successful. That's why
(38:30):
we're here talking about it is because all the cells
that make us and all the cells that have made
everything around us are plodding away relentlessly doing their thing.
And that's something that scientists can now kind of take
advantage of in order to observe ourselves from the outside
and to see what it is that makes them so special. Yeah,
(38:50):
I don't know. I'm very touched by that in a way.
I think there's something... comforting, I suppose, about it. That
life is, life literally finds a way, right? That life
is just unstoppable.
Speaker 1 (39:04):
Claire Evans, thank you.
Speaker 2 (39:05):
Thank you so much for having me.
Speaker 1 (39:24):
For Tech Stuff, I'm Osvald Oschin. This episode was produced
by Eliza Dennis and Tyler Hill. It was executive produced
by me and Julian Nutter for Kaleidoscope and Katrina Norvell
for iHeart Podcasts. Jack Inslee mixed this episode and Kyle
Murdoch wrote our theme song. A special thank you to
all our listeners. Please rate, review and reach out to
us at techstuffpodcasts at gmail.com. We love hearing from you.
Welcome to Tech Stuff. I'm Oz Veloshian. There's only one
way to put this. I read one of the craziest
articles in recent memory, recently in Wired. It's called AI
is Dead, Organoids are Alive. And it's a look inside scientists'
attempt to grow computers powered by human cells grown in
a lab. Written by Claire L. Evans, a journalist, a
(00:37):
speculative fiction writer, and a musician with the band Yacht.
who also had some remarkable experiences reporting this piece that
she's here to share with us today. Claire, thank you
for joining.
Speaker 2 (00:47):
Oh, thank you so much for having me.
Speaker 1 (00:49):
So talk about organoids and this quote that you have
early in the piece, I'm going to let you in
on a secret. Every cell in your body has the
potential to get smarter.
Speaker 2 (01:00):
Yes, that's technically true. You can take any cell from
the human body, normally skin cells, but also hair, follicle cells, teeth, blood,
these all work. You can introduce those cells to a
special cocktail of proteins. Those cells will revert to their
embryonic state. They will become stem cells. They will become pluripotent,
(01:20):
which means capable of turning into many other different types
of cells. And you can turn those cells into neurons
and from there build all kinds of interesting things.
Speaker 1 (01:30):
So what is an organoid?
Speaker 2 (01:33):
Okay, well, big picture. An organoid is... essentially a small
spherical glob of human cells that reproduces on some different levels, structural, molecular,
developmental levels, some aspect of the body part from which
those cells were drawn. So you can think of it
as like a mini model of a human organ made
from the cells that constitute that organ. You can make
(01:55):
stomach organoids, for example. You can make cardiac organoids. You
can make tear gland organoids, and you can make brain organoids.
Speaker 1 (02:03):
The brain ones are the most fascinating ones, right?
Speaker 2 (02:05):
The brain ones are very interesting, but let us not
forget the others.
Speaker 1 (02:08):
We need all the organs.
Speaker 2 (02:12):
We need all the organs and it's fascinating. I mean,
heart organoids will beat, you know, tear gland organoids will
cry and brain organoids will, I mean, I wouldn't say
they think, but they definitely create synaptic connections. They crackle
with all kinds of electrical activity. They form these basic
structures that are similar to like a fetal brain. They
do brain things just on a much, much smaller scale.
Speaker 1 (02:34):
But you can take a skin cell and turn it
into a brain organoid?
Speaker 2 (02:37):
You can take a skin cell and turn it into
a neuron and then put enough of those neurons together
in a little dish, keep them warm and happy and well-fed,
and they will do what cells do, which is just divide, multiply, cohere, aggregate,
and form these little structures. There's an upper ceiling on
how big they can get because they don't have vascular system.
They don't have veins. to kind of cycle nutrients in
and clear out toxins. So they can only grow to
(02:59):
about five millimeters in size before they develop what's called
a necrotic core and suffocate from the inside out. But
within that tiny scale, you can have like five million neurons.
And that's about the size of a bee's brain. So
you can do lots of really interesting neuroscience research and
pharmaceutical testing with just that.
Speaker 1 (03:17):
What got you onto this story?
Speaker 2 (03:19):
Oh, there was a big splashy, I mean, I'm following,
you know, all the publications within this sort of space
of the overlap of computation and biology. It's my beat.
I'm very interested in those places where technology touches life
and vice versa. I think that's where technology is headed
because I believe that there is a limit to what
we can do with silicon. And I think there's also
a limit to how much silicon there is left in
(03:42):
the world to build things with. I mean, We're literally
running out of sand. We're running out of minerals. These
things are not renewable. So I'm really interested in where
biology can come in and provide alternative ways of not
just thinking about technology, but also alternative substrates and ways
of building technology that is more resilient, more efficient, more
in line with how the world already works rather than
(04:02):
the sort of artificial construction we call computing. Anyway, that's
neither here nor there. I have been following this intersection
for a long time, and there was a big splashy
press push out of Johns Hopkins University a year and
a half ago, pushing forward this idea of what they
were calling organoid intelligence. So organoids have been around since
like the early 2000, 2008, 2009. And they've been a
(04:23):
staple of basic research. But all of a sudden, there
was this outpouring of research around like, how can we
connect these organoids to computer systems and do computer things
with them? And they were calling it organoid intelligence. They
were trying to make a big swing to kind of
name this field and bring a lot of talent to it. Yeah, OI.
Speaker 3 (04:40):
OI.
Speaker 2 (04:40):
So I was like, this is something interesting. I don't
know how much of this is hype, how much of
this is just scientists trying to get press and funding
by sucking on to the hype around AI, or how
much of it is actually really going to transform how
we think about computing. And that's, yeah, it just nagged
at me for a long time until I finally got
approval from my editors to go figure it out.
Speaker 1 (05:00):
How are they actually used today? I mean, how much
of this is about the future where groups of brain
organoids can replace silicon-based chips to do computing, and how
much of it is more like these have a purpose
for drug testing or for other types of laboratory experiments?
What is the actual use case today, and where's it going?
Speaker 2 (05:20):
Well, obviously, we're a very long way away from living
AI systems. And, you know, there's like in all kind
of biology and basic research, not an enormous amount of
funding in this space compared to the kinds of resources
that are being put towards silicon-based intelligence. But we are
making quite significant strides. So, I mean, currently the state
(05:41):
of the art is we can grow brain organoids very
consistently at scale. We can grow them directly onto microelectrode arrays.
I say we, I mean like humanity. Obviously, I'm not
doing this. Onto these kind of electrode arrays, and then
we can stimulate them with electricity because very conveniently the
human brain responds to electricity as do conventional computing components.
(06:02):
So we can stimulate these neurons and then they will
sort of respond in kind and we can measure those
responses and in that process develop a kind of rudimentary
form of programming. So there are a number of researchers
who are training neural systems, both three-dimensional organoids but also
flat two-dimensional neural cultures, to do basic tasks that would
(06:23):
normally be done by AI, things like image classification, text recognition.
There's a very splashy.
Speaker 1 (06:29):
But that's not happening today already, right? Yeah, yeah, that's
totally doable.
Speaker 2 (06:32):
It's just, it's inconsistent and slow.
Speaker 1 (06:34):
Right.
Speaker 2 (06:36):
But it is absolutely possible.
Speaker 3 (06:37):
Wow.
Speaker 2 (06:38):
Yeah. I mean, obviously, it's not like neurons are using
their eyeballs to look at pictures of text and saying this, this,
or this, but the text is being translated into electrical
signals and then fed to those organoids. The organoids are
responding in kind and translated back. So there's a movement
between analog and digital that happens, you know, with all biological... interfaces.
You have to move from our world of bits and
(06:59):
bytes to their world of biochemistry and electricity and back again.
But we're figuring out how to do that. So it
is possible to do that. There is a startup in Australia.
Speaker 1 (07:08):
I like that you described our world from the point
of view of being a computer and their world from
the point of view of being an organoid.
Speaker 2 (07:14):
Yeah, I mean, the thing that I.
Speaker 1 (07:15):
They inverted us and them, human-machine paradox.
Speaker 2 (07:18):
I know. Honestly, it's so disorienting thinking about this stuff because...
Our cells make us, right? I mean, we're all made
of millions and billions of cells, but also they are
perfectly happy living without us. You can take these neural cultures,
put them in a dish. If you keep them fed
and warm, they will just live essentially forever without any
(07:39):
intervention from us. Like if you make an organoid out
of your own skin, is it you or is it
not you anymore? There's this sort of autonomy that cells have.
And when you sort of separate them from the human
system and let them do their own thing, they have
their own kind of onboard capacities that are unrelated to
the organism they form at scale. It's kind of disorienting
(08:01):
ontologically and bizarre.
Speaker 1 (08:03):
You had this great quote, brain organoids are creepy. They
muddy the line between person and thing, which is like
the difference between humans and animals or the living and
the dead. It's a fundamental distinction. The trend turns culture.
I thought it was a really fascinating way of putting it.
Speaker 3 (08:15):
Yeah, yeah.
Speaker 2 (08:16):
That's something that came from some sociological research on kind
of the way people respond to organoids. An interesting, I think,
actually consequence of this piece is when I was writing it,
I was talking to a lot of sociologists of science
and bioethicists who were really invested in the question of
brain organoids. And they all kind of more or less
told me, yeah, people don't think brain organoids are weird.
(08:37):
people understand that it's for the greater good. It's for science.
They're not unsettling. They're not eerie. They're not that strange.
There's not going to be a lot of pushback against
this technology when it makes the leap to computing because
people kind of understand biomedical research. Everybody was very confident
in that. And then I published this piece and the
response has been across the board, people being like, ah,
(08:58):
you know, freaking out and being kind of horrified on
some fundamental level about the idea of a computer having
some living cells in it, I think people find it
much more morally objectionable than I think the bioethicists would
be comfortable to admit. So that's been an interesting consequence.
Speaker 1 (09:17):
Are they just small human brains?
Speaker 2 (09:20):
Well, if you talk to anyone in this space and
you call these things mini brains, they get really touchy.
They go, these aren't mini brains. These aren't mini brains.
These aren't even brains. I mean, a human brain has
171 billion cells, including both neurons and glial cells, which
are kind of the scaffolding. An organoid has maybe five million.
There's an enormous difference in scale. And what makes a
(09:43):
brain a brain is, I mean, a subject of ongoing debate, obviously. But,
you know, there is the general consensus that some emerging
capacity comes at this scale that is maybe not legible
at such a small scale. There's also long been this
sort of ambivalence, I guess, or even like outright distaste
(10:04):
on the part of the scientific community for talking about
questions of consciousness or sentience or even really intelligence.
Speaker 1 (10:11):
Not from the AI community.
Speaker 2 (10:13):
Well, the AI community is all for it. They think
they're so ready to ascribe sentience to absolutely anything. you know,
put a couple googly eyes on a laptop and all
of a sudden it's a person.
Speaker 1 (10:21):
Let me ask you about the headline of the piece,
AI is dead, organoids are alive. I mean, I guess
your editor chose the headline, but is that, what are
your thoughts on it?
Speaker 2 (10:31):
I mean, I think there is something really interesting about
the way that neurons process information that silicon systems will
never be able to achieve. I mean, neurons have the
capacity to grow and prune their synapses based on their
experience of the world. I mean, In the case of
an organoid, that experience is electrical signals or maybe some
(10:52):
chemical stimulus in a dish. It's not the same thing
that we think of as experience at the human scale.
But it is like an embodied experience, an embedded experience
of the world. And some philosophers call that nano-intentionality. It's
essentially the idea that living matter can respond to its
environment in real time. and yeah i mean ai systems
(11:15):
even the most sophisticated ai systems they're still built on
these sort of static elements which are not you know
self-assembling they're not responsive to the world they're not uh embodied.
Speaker 1 (11:25):
The chips aren't but the models are.
Speaker 2 (11:27):
No yeah i suppose so i mean i just think
there's like a i don't know there's just like a
sort of fundamental i guess sort of philosophical distinction between
these substrates whether you want to call that dead versus
alive i mean that's an editorial choice but I mean,
I do think the comparison between, you know, rocks and cells,
because I mean, computers are just rocks, right? And cells
(11:50):
is an instructive one.
Speaker 1 (11:52):
Talk about the experience of actually reporting the piece. I
want to know about your trip to the UC San
Diego Stem Cell Institute.
Speaker 2 (12:01):
Yes. So I had a great fun reporting this piece,
although I will tell you that like all cell culture
labs pretty much look the same. You know, they're not
like full of like bubbling beakers and brains and jars
like you would imagine. You know, it's incubators that basically
look like mini fridges with trays and trays and trays
of these like nutrient wells that basically look like contact
lens solution and little globs floating in them. Those are
(12:24):
the organoids. You know, it's not hugely glamorous. At UCSD,
they do have some robots. So there are people there
who are working on organoid controlled robots, which is quite interesting.
Speaker 3 (12:34):
Wow.
Speaker 2 (12:35):
They're doing a lot of really kind of strange and
interesting work. They're, for example, creating genetically modified Neanderthal brain
organoids to understand the difference between human and Neanderthal brains.
Speaker 1 (12:45):
Whoa.
Speaker 2 (12:46):
How do they do that? I'm not entirely sure, to
be honest with you.
Speaker 1 (12:49):
Are they from fossils? Are they sequenced DNA?
Speaker 2 (12:52):
Yeah, I think they are just... you know what i
don't know i don't know 100 no but there's an
entire neanderthal organoid department within.
Speaker 1 (12:59):
The ucsd stem cell research crazy.
Speaker 2 (13:02):
Yeah they're also sending organoids to space to understand how
like radiation affects human astronaut brains i mean the thing
is that you know organoids provide a basis for studying
the brain in so many different ways i mean the
obviously the ai stuff is splashy and exciting and we
love robots and we love computers but We know very
little about how the human brain is even formed in utero.
(13:25):
Because of ethical guidelines on research, we don't really know
what happens after about 14 days. Between 14 days and
nine months, we have no idea how the human brain
comes together. Everything we know about it, we've learned from
analogy through studies of rats and fruit flies and stuff.
So an organoid, which is essentially like a fetal mini, mini,
mini brain, allows researchers to understand basic things about human
(13:47):
brain development. And that's a lot of what's being done
in that particular lab. It's like the study of human
brain development. And the AI organoid piece is just one
other way of getting at those questions. Because if you
can train, quote unquote, you know, a wired up organoid
to respond to certain electrical stimulus, to perform certain tasks,
(14:08):
for example, playing a simple video game, then you can,
you know, expose that organoid to different environmental factors, to
different toxins, to different pharmaceuticals. and understand how those things
affect that little nascent brain's capacity to respond to those tasks.
So it's another piece of a toolkit for understanding how
(14:28):
the brain works.
Speaker 1 (14:30):
So who is Alison Mowatry?
Speaker 2 (14:32):
Alison Mowatry? Alison Mowatry, yeah. He's a developmental biologist at UCSD.
He's a leading organoid researcher. He's part of the sort
of larger organoid intelligence effort or cohort, but he's fundamentally
more interested in things like autism, human brain development.
Speaker 1 (14:49):
His son is autistic, right?
Speaker 2 (14:51):
Yeah, his son is autistic. And he actually has created
organoids from his son's cells in order to understand how
his son's brain works, which is really fascinating to me.
And I asked him, is it weird to you to
be looking down a microscope at a miniature brain made
out of your own son? And he told me that
(15:12):
he has to kind of just disassociate in order to
do the research and not get too emotionally invested in it.
Speaker 1 (15:19):
How did actually going to labs change your understanding of
the story?
Speaker 2 (15:22):
I think the most beneficial thing for me about going
to a lab is actually being able to sit down
and talk to scientists face to face and get a
sense of their vibe. Because, I mean, I don't have
a background in neuroscience or computer science for that matter.
So there's only so much I can really get out
of reading academic papers. I mean, I try my darndest,
but at the end of the day, going up to
(15:43):
the scientists and saying, how exactly did you do this
and what does it mean? I mean, of course, I
ask all the important questions like, what happens if you
eat an organoid? And I think it was Alison Mowtri
who told me that nothing happens if you eat an organoid.
You'll just digest it. But if you are working in
a lab with an organoid that was made from your
own cells... That's extremely dangerous because if you get any
(16:06):
part of that organoid back in your body by accident,
your bloodstream, for example, through a cut or a lesion
of some kind, it will reenter your body, having developed
outside of your body, and it will start dividing and
multiplying and it could cause cancer because that's essentially what
cancer is, is cells going rogue and dividing and multiplying
outside of the multicellular project of the body. So it
(16:28):
will have become independent, returned within... And gone rogue, which
I think is just absolutely fascinating and strange. But yeah,
I mean, my favorite thing about this kind of research
is just going into labs and asking the wackiest questions
I could possibly think of to sort of throw these
people off balance. And also, you get really fascinating answers. That,
to me, is such a strange reality of cellular research.
(16:52):
You can't work with your own cells because they might
infect you.
Speaker 1 (16:55):
Is mortuary making progress on the autism question?
Speaker 2 (17:00):
Yeah, I think so. I mean, I think he's studying
how the development of an autistic organoid differs from a
neurotypical organoid. Obviously, it's a really complicated thing to entangle.
But yeah, I think he's definitely making progress, looking at
different kinds of therapies that might emerge from this. And
he seems very optimistic that he can make a real difference.
Speaker 1 (17:19):
Who told you that you don't need permission to torture
as many flies as you want? And what does that mean?
Speaker 2 (17:26):
That was this amazing sociologist, John Evans, who's also at UCSD.
who has made a career of like kind of being
a sociologist of biology and bioethics. So he was a
great outside observer to talk to about this stuff. Yeah.
What he was saying was basically that the regulation around
experimenting with this stuff is a little bit, it's a
little bit unclear. Like there are very specific roles about
(17:47):
working with different kinds of animal models, right? Like if
you're going to do experiments on rats or apes, like
you have to go through all these different, you know,
reporting guidelines and ethical guidelines and You know, there are
ways that you appropriately euthanize an animal after you work
with them, things like that. There's no such regulations in
place for organoids. They're kind of equivalent to working with invertebrates,
which is also kind of unregulated. I mean, that's changing
(18:10):
a little bit now because there's new research about like
pain reception and sentience in insects. But from a legal standpoint,
you don't need to get permission to, you know, torture
as many fruit flies as you want. That's why fruit
flies are very common. in biology labs. And it's the
same thing for organides right now. You don't necessarily need
legal approval. It's not understood that they feel pain, for example.
(18:33):
So there's no real concerns around that for now. But
these organides are getting more and more complex. And now
that we're connecting them to these electrode arrays and stimulating them,
you could make an argument that they're having experiences, which
has an effect on how we think about sentience and consciousness.
I mean, there are philosophers of mind who think that
(18:54):
these things sentience and consciousness are a consequence of experience,
of an embodied experience of the world. It's also possible
now to create what are called assembloids, which is where
you take organoid structures from different parts of the body
and kind of glob them together. So you can make
an organoid that can see, for example, or at least,
you know, perceive light. So there's different sort of forms
(19:14):
of input now that we can create. And those, I
think it's getting more and more kind of morally, or
not morally, but ethically gray. in terms of what we
feel is permissible to do with these little human-not-human cellular structures.
Speaker 3 (19:28):
Can they learn, and what does it mean when they learn?
Speaker 1 (19:47):
Can they learn? And what does it mean when they learn?
Speaker 2 (19:50):
Yeah, they can learn for sure. You can kind of
train them. So actually the best, I think, research in
this comes out of this biocomputing startup in Melbourne called
Cortical Labs, who basically did a series of experiments that
have served as a proof of concept for how one
can program these systems. There's a theory in neuroscience called
the free energy principle. It's way above my pay grade,
(20:13):
but I can try in the simplest of terms. It's
essentially just the idea that self-organizing biological systems like predictable stimulus,
they will rearrange themselves to avoid chaos because that way
it is easier to anticipate and predict change. It takes
more energy to respond to a radically changed environment than
(20:34):
it does to one that is regularly stimulating. And so
you can essentially subject, expose neural cultures to chaotic stimulus
and they will do everything they can to avoid that.
So If you pair regularly spaced signals with an input
that you want, like for example, in the case of
this research, it was to play the video game Pong.
(20:57):
So if the electrical signals representing the ball hitting the
paddle are associated with some like regularly pulsing input, the
neurons will rearrange themselves in order to create that outcome
as much as possible. So you essentially reward them with
regular electrical stimulation. It's hard to say, like, do they
like that? Is it something that they enjoy? You know,
(21:20):
these kinds of words are ambiguous at best, but they
will certainly rearrange themselves to create those conditions. So that's
a kind of a proof of concept for this neuroscience theory.
It's also has proven to be a useful way of programming.
I'm told there are other ways that are being developed,
but it's really like very early days. And there are
a number of different companies now who are creating these
(21:42):
kind of networked organoid systems. So they have cultures of
organoids kept alive in these, you know, little kind of
biological computers. Those biological computers are connected to the internet,
you know, a neural server, if you will, which sounds
very sci-fi, but essentially what it means is that it
allows people who are wanting to work with organoids in
this capacity to do it remotely. It's kind of like
(22:04):
actually quite analogous to like the early days of, you know,
the internet when researchers wanted to access resources at computers
and different sites on the ARPANET, they would do that
remotely rather than having to like travel there and do it.
So There are now ways of remotely programming these systems
and studying their responses in all kinds of different ways.
So there's lots of different research being done all over
the world on these networked neural servers to essentially articulate
(22:29):
what the programming language of biology will be. And it's
as yet unknown. I mean, electrical signaling is definitely the
most efficient way, but there's also an enormous amount of
neurotransmitter chemicals in the human brain that neurons use to
communicate with each other. It's possible that we might be
able to do so chemically. That's a little bit slower
and more diffuse, but there could be applications for that
(22:50):
as well.
Speaker 1 (22:51):
And you did this, right? I mean, you interacted with
organoids over the internet.
Speaker 2 (22:56):
Yeah, I played Pong with some neural cultures online. I know,
it's pretty wild. I mean, I needed to be walked
through it by, you know, an engineer at this company
because these neural cultures are addressable in Python. So there
is some programming. It's not like you're just playing online,
you know, as you would like any kind of online game.
But yeah, you run them through these trials repeatedly and
(23:16):
over time they get better and better at hitting the
paddle back and rallying. And over time, yeah, they improve.
They're not very good at it. They're still not very
good at it. And they can play Doom now. That
was like a big viral news story some months ago.
Similar technique, just more complex input. They're also not very
good at that either, but they can do it. And
(23:39):
that's really like a starting point.
Speaker 1 (23:41):
Was it uncanny for you? Or was it like you're
in a Waymo and it's sort of uncanny for the
first 20 seconds and then you go back on your phone?
What was the personal experience for you of interacting with
these organoids?
Speaker 2 (23:53):
It's very surreal because I just felt this weird burden
of responsibility. I mean, I had access to this beta
server system where you could control all the environmental factors.
You could control the CO2 balance and the temperature of
the server in which the neurons were being held. And
I was highly conscious of the fact that if I
just like clicked in the wrong place, I might kill them.
(24:15):
And that is something that, I mean, I say this
in the piece, but it's, that's a new paradigm in computing.
Like you don't normally expect when you do something wrong
on a computer that something dies as a consequence of
that error. And I don't know, I felt very, I was,
I was treading very carefully. I felt like a bull
in a China shop. You know, I was like, I just,
(24:36):
I want to make sure these organoids stay safe and
happy in their little in their little petri dish in
australia yeah strange it's a it's a strange feeling to
interact with something alive online i mean i suppose it's
not the first time i suppose like webcams of nature
you know you have like these portals into the living
world but so rarely do you have the capacity to
actually physically interact with something that is if not sentient
(24:59):
then alive.
Speaker 1 (25:01):
Is the melbourne is that where cl1 is yes yes
and one of the creators of CL1 said CL1 is
the theoretical neuroscience as the Large Hadron Collider was the
theoretical physics. What does that mean?
Speaker 2 (25:16):
Yeah, I mean, that's kind of that thing I was
talking about earlier about how they figured out a way
to program these neurons based on the theory of the
free energy principle, which is this neuroscience theory that they
essentially tested in silico, in utero in silico. I don't
even really know how you would describe what it is.
But I mean, yeah, they were able to kind of
(25:37):
take an idea from theoretical neuroscience, translate it into a
series of commands, interact directly with the living system, and
then see that that theory was in fact true. So
that was a way of using the CL1 to test
basic neuroscience theories, which is really, I think, exciting for
a lot of people. It's a little bit grand of
a claim, of course, but I don't think it's incorrect.
(26:00):
These are self-contained systems for testing theories of mind. It's
truly wild. And it's so interesting to talk to these
people because they have actually like a, you know, I
think some of the response to the Wired piece from
the general readership was kind of like, this is unholy.
These people have no respect for life. You know, there's
a sacred spark in the human mind and we are
(26:23):
befouling it by putting it in computers and instrumentalizing it
or objectifying it. And I think all of that is
absolutely valid and based on the track record of biomedical
industry and the tech industry a very fair assessment. But
I did find that talking to these people, they're all
incredibly sincere about wanting to understand how intelligence works, wanting
(26:46):
to understand the secrets of biology in a kind of
synthetic and constructive manner. I think the history of biology
has been, it's a very reductive science. Scientists have tried
to like understand all the little tiny pieces and how
they fit together. There's been this belief for a long
time that if we could just look in a microscope
small enough, we'll see how it all works. And at
(27:09):
the end of the day, there's certain things you can
only understand through building. You can only understand in a
kind of synthetic way. And in a way, I think
these people are putting together these systems and they're developing
a knowledge of fundamental underlying structure of intelligence that they
could only really get by doing what it is that
they're doing. Now, what comes next, you know, 10 years
(27:31):
from now, 20 years from now, how comfortable we may
be or not be with living systems? Those are other questions.
But right now, at least, I feel like a lot
of the stuff is just driven by a genuine desire
to understand intelligence and a genuine respect for the complexity
of biological intelligence. I mean, a lot of these people,
they're building these hybrid computational living systems, but they know
(27:53):
that AI, as it's currently instantiated, is fairly limited. It's
trying to emulate something that is so much more complex
than most engineers are willing to acknowledge. And only by
starting to kind of work with those living materials are
they really coming to understand just how much biology is
(28:15):
doing that we aren't even conscious of or capturing or
even close to modeling in synthetic systems.
Speaker 1 (28:23):
But is the Holy Grail to replace silicon computing with
neural computing or organoid-based computing because it's so much more
energy efficient? Or is the holy grail to actually truly
understand how the human brain works?
Speaker 2 (28:39):
Can't it be both? No, I don't know. I mean,
I think different people have different intentions. And that was
something that was really clarifying about reporting the piece is that,
you know, I talked to a lot of different scientists.
Some of them, you know, they're interested in this stuff
because they want to understand how the brain works, how
the brain is formed. Others want the stuff to work
so that they can do more accurate Alzheimer's research or
(29:01):
test pharmaceuticals. Some of them are interested in the computational questions.
I mean, there's a wide kind of gamut of approaches.
But I do think that's all kind of grounded in
a healthy respect for the complexity of life. For some,
I think, yes, the end goal is to create AI
systems with living materials that are competitive with AI systems
(29:23):
made from silicon. I think everyone is conscious that that's
a very, very long way away. And in a way,
sometimes the more we learn about biology, the more we
realize that we have yet to learn. So I think
they're all humbled by that. But the hope is perhaps that, yeah,
both those things can be true that we can build
computer systems and in the process learn a lot about
(29:43):
how intelligence works.
Speaker 1 (29:46):
Can you kind of help me understand the difference between
what the researchers hope will eventually happen and what's actually
been demonstrated with organoids to date.
Speaker 2 (29:57):
Yes. Well, I mean, to be fair, I think a
lot of the researchers are pretty measured in their estimations.
And in my experience of talking to biologists is that
they're really any scientists is that they're quite reticent to
be speculative about these things. I mean, they have ideas
about what questions would be cool to ask and what
things they think are going to get them funding. But
none of them is walking around saying, like, in the future,
(30:17):
computers are going to be made out of brains and
it's going to be impossible to tell the difference between
computers and people or whatever. Nobody's making those claims. they're
making much more prescribed and limited claims. So there's not
an enormous gap, frankly. I mean, they're interested in, yeah,
being able to use these computing organoid systems to ask
more pointed questions within their own realms of research, if
(30:42):
that makes sense. But I think all the grand claims
come from, you know, the university PR departments and the
journalists and the people like us who want to kind
of look at this stuff and go, oh, this is
where it's headed rather than kind of sit with the
complexity of where it is.
Speaker 1 (30:59):
And one of the biggest obstacles is blood.
Speaker 3 (31:01):
Yes.
Speaker 2 (31:02):
Blood is really important. Vascularization is really important. There's an
upper ceiling for how big an organoid can get because
they don't have circulatory systems. They don't have veins. They
have no way of filtering out toxins and bringing in nutrients.
So there's some like Preliminary research being done now in
kind of artificial perfusion systems, you know, building these like
(31:23):
tiny microfluidic networks to kind of circulate nutrients throughout the
inside of the organoid. There are people who are building
vascular organoids, so like making organoids from like vein cells
to create these kind of rudimentary vascular structures. So we'll
probably break past that threshold in some way or another soon.
But for the time being... Yeah, they die after a
(31:46):
certain size because the cells on the inside of the
organoid suffocate without access to nutrients.
Speaker 1 (31:53):
And what are the other big obstacles?
Speaker 2 (31:56):
Funding, always, especially in the US.
Speaker 1 (32:00):
So there hasn't been a rush of capital around the
AI stuff that's also funded a lot of this?
Speaker 2 (32:05):
I didn't get the impression that there has been, no.
I mean, there are some startups in this space. there's
this company in Australia, there's a company in Switzerland that's
doing this. I think they are relatively well capitalized, but
not on the scale of like literally any AI company. Funding,
you know, within the kind of biomedical research context, basic
(32:26):
research is a real struggle right now in the US, obviously.
There is, however, like a turn towards organoid-based research in
the US because of a movement away from animal research models.
So the NIH just like basically said that it wouldn't
approve any grants that didn't include a like organoid type
(32:47):
system wow.
Speaker 1 (32:48):
It's a big stimulus yeah because there's.
Speaker 2 (32:51):
Just been this general kind of political and sociocultural move
away from animal testing which i mean organoids are great
in that regard because you know most especially like neurochemical
drugs uh psychiatric drugs fail in human trials because they're
tested on rats and you know rats don't get depressed
as far as we know so there is a limit
(33:12):
to what we can learn from animal models. And organoids
tend to be like a lot more representative chemically and
molecularly of what's happening in the human brain. So that's
a good thing. But yeah, I mean, funding is always
a constraint. I think, you know, the ethical questions are constraining.
I think for like basic organoid research, not so much,
but for this kind of computational stuff, I think there
(33:34):
is a lot of trepidation A lot of the, like
the Johns Hopkins team, for example, works with embedded ethicists
and is always touting the fact that they work with
embedded ethicists because I think they're sensitive to the fact
that people might get kind of squicked out by this
stuff and that could imperil their position. And so they
take everything really incrementally and, you know, they have regular
(33:56):
meetings between the people who are working in the wet
labs and the people who have, you know, who are
asking these kind of ethical sociological questions. They're very earnest
about that. It seems that they very much enjoy these
conversations and have this kind of constructive way of approaching it.
That being said, I mean, the bioethicists, you know, they're
embedded within these same biomedical institutions. So they might not
(34:19):
have the most clear outside perspective on how people in
the real world are going to respond to these things.
So that's a limitation for sure.
Speaker 3 (34:25):
Yeah.
Speaker 2 (34:28):
Those are the major ones, I would say.
Speaker 1 (34:30):
Just before we wrap, can you quickly explain the nature
of consciousness and how... i have to ask you the
consciousness question yeah.
Speaker 2 (34:41):
I mean the consciousness question is the question right and
it's one that absolutely none of the scientists want to
talk about i mean every single scientist i asked it's
like i was very careful to ask that question last
after i had proved my competency and all the kind
of bio biomedical aspects of this because they really don't
like talking about it not because they're not interested or
they don't like believe it's important because i think it's
all anyone ever asked them about you know and i
(35:02):
think they have a very different understanding of what consciousness is.
They're much more reluctant to label anything as being conscious
because they, I don't know, I think they work with
living matter all the time. They work with cells all
the time. They know what cells can do and can't do.
They're not precious about it. But yeah, I think the
(35:24):
question is they're, you know, somewhere between 5 million cells
and 170 billion cells, like something happens, right? Something called
consciousness dies. emerges. Whether that's possible in a dish alone
without external stimulus from the world, without an embodied experience
of the world, without parents or an upbringing or relation
with other animals and people and sensory experience, whether that's
(35:48):
possible in isolation is like an open question in philosophy
and in biology. Nobody really knows. I think a lot
of the reluctance that I encountered with talking to biologists
about this question is that there's no like quantifiable definition
of consciousness. You know, it's something we've been debating since
ancient times and nobody really knows how to name it.
(36:12):
And that makes it really difficult to say whether something
is conscious or not conscious. I mean, for example, an
organoid is about the size of a bee's brain. Do
you think of a bee as a sentient organism, a
conscious organism? Even within science, there's a huge gamma of
responses to that question. I personally would think a bee
is sentient. but others might not. So where we draw
(36:34):
those lines is ultimately quite personal and socially prescribed and philosophical,
and it's going to make it really difficult to guide
this research ethically. I mean, I think everybody's keen to
err on the side of caution with this stuff, but
it does feel inevitable that at some point along the road,
(36:55):
as these things get older, more mature, more complex, As
we start stimulating them and giving them sensory experience, some
thresholds will be crossed. And in the absence of any
way to infer conscious experience from the outside, we have
to be very careful. For the time being, I don't know.
(37:18):
I really don't know. It does seem to me, though,
that when you are giving these cells experience, you're putting
them well on the path towards something like consciousness even
if it's like a micro shade of that it's got
to be a piece of that puzzle and.
Speaker 1 (37:37):
One of the most fascinating things in your piece i
think is that these organoids and cells their primary motivation
is to connect apparently.
Speaker 2 (37:47):
Yeah yeah well neurons that's what they do right they
forge connections with each other every neuron has many many
connections with every other neuron it's it's their cellular imperative
so you put them together That's what they do. They
form these kinds of aggregations in the absence of a body,
in the absence of a brain, they'll still do what
(38:08):
they do. And I find that really beautiful. Like the
fact that all of our cells have these, I mean,
this is kind of like loaded language, but have these drives,
have these capacities, I guess, that kind of don't even
require us to be there in order to transpire. They
just do what they do. They're unfailingly resilient in that way.
And that's why life has been so successful. That's why
(38:30):
we're here talking about it is because all the cells
that make us and all the cells that have made
everything around us are plodding away relentlessly doing their thing.
And that's something that scientists can now kind of take
advantage of in order to observe ourselves from the outside
and to see what it is that makes them so special. Yeah,
(38:50):
I don't know. I'm very touched by that in a way.
I think there's something... comforting, I suppose, about it. That
life is, life literally finds a way, right? That life
is just unstoppable.
Speaker 1 (39:04):
Claire Evans, thank you.
Speaker 2 (39:05):
Thank you so much for having me.
Speaker 1 (39:24):
For Tech Stuff, I'm Osvald Oschin. This episode was produced
by Eliza Dennis and Tyler Hill. It was executive produced
by me and Julian Nutter for Kaleidoscope and Katrina Norvell
for iHeart Podcasts. Jack Inslee mixed this episode and Kyle
Murdoch wrote our theme song. A special thank you to
all our listeners. Please rate, review and reach out to
us at techstuffpodcasts at gmail.com. We love hearing from you.
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