How to make your organs last longer | Quin Wills | TEDxNoVA
Summary
TLDRIn this insightful talk, the speaker introduces 'Betty,' a revolutionary machine that can sustain a human liver outside the body for up to five days, allowing for advanced liver assessments before transplants. The presentation delves into cutting-edge RNA medicines designed to reprogram donor organs, potentially transforming the future of organ transplantation. It also touches on the challenges of developing therapies for chronic liver disease, advocating for a new approach that leverages AI and human collaboration to expedite the discovery and testing of life-saving treatments.
Takeaways
- 🔬 Betty is a machine that can keep a human liver alive outside the body for up to a day, used in clinics to assess liver health before transplants.
- 🏥 The Liver Intensive Care Unit (IU) in Manhattan is a unique facility where scientists, technologists, and clinicians work on extending the life of livers to five days using advanced technology.
- 💊 The project involves injecting livers with RNA medicine, a sophisticated method that can alter gene behavior and target specific liver cells, representing a new approach to liver medicine.
- 👨⚕️ The speaker has early-stage liver disease, highlighting the personal connection to the work and the urgency of finding solutions for liver health.
- 📈 Shocking statistics: one in three people may have liver issues, and one in six of us could live to be a hundred, facing chronic diseases of aging like liver failure.
- 🌐 The aging population is increasing, with one in four people expected to be over 60 in 30 years, raising concerns about the longevity and health of our organs.
- 🔬 The process of creating new medicines involves three steps: generating hypotheses, testing them, and conducting clinical trials, each with its own challenges.
- 🤖 AI and deep learning are used to analyze liver biopsies, creating detailed atlases from genes to cells to tissues, helping understand liver function and dysfunction.
- 🧪 Labs in Oxford and Taipei are working on human liver models, using both bottom-up and top-down approaches to study liver function and develop therapies.
- 💉 The goal is to develop therapies that can repair livers, potentially eliminating the need for transplants by using medicines that target specific liver cells.
- 💻 Computational models and AI avatars are being developed to predict liver responses, accelerating the process of developing new therapies and reducing costs.
Q & A
What is the primary function of the machine called Betty?
-Betty is a machine designed to keep a human liver alive outside the body for up to a day. It is used in clinical settings to assess the health of livers before they are transplanted into another human being.
What is the purpose of the Liver Intensive Care Unit (LICU) in downtown Manhattan?
-The LICU in downtown Manhattan is where a team of scientists, technologists, and clinicians are working to modify the use of liver machines to keep livers alive for not just one day, but up to five days. The goal is to treat organs as patients and improve their viability for transplantation.
What is the significance of the RNA medicine used in the liver machines?
-The RNA medicine is a sophisticated form of treatment that is programmed to change the behavior of specific genes and target only very specific cells in the liver. This represents a new way of thinking about liver medicines, potentially reprogramming donor organs that are too old or diseased to be suitable for transplantation.
Why is there a focus on the liver in this context?
-The focus on the liver is due to the speaker's personal experience with early stages of liver disease. Additionally, liver disease is a common condition that can lead to the need for a liver transplant, which is a critical and often life-saving procedure.
What is the 'scary statistic' mentioned in the script about liver transplants?
-The 'scary statistic' is that if you end up on a liver transplant waiting list, there is a good chance you will die before a healthy enough liver is found for you.
What is the speaker's perspective on the aging population and its implications?
-The speaker views the aging population as a potential 'aging epidemic' that could be as significant as global warming. The challenge is to create a society where people can live healthy lives into their 100s, which involves rethinking healthcare and treatment for chronic diseases of aging.
What are the three steps in developing a therapy to reduce scarring in human livers as described in the script?
-The three steps are: 1) Idea phase (hypothesis generation) where potential genes affecting scarring are identified. 2) Testing the hypothesis and making a medicine, which often involves animal testing and can take many years. 3) Clinical trials in humans, which are lengthy, expensive, and often fail.
How does the speaker propose to address the challenges in developing transformative medicines for chronic diseases of aging?
-The speaker suggests addressing the challenges by learning more about human biology, reducing reliance on animal models, and improving clinical trials to be less time-consuming, less expensive, and less risky.
What role does AI play in the process of studying and treating liver diseases as described in the script?
-AI plays a crucial role in analyzing large and complex datasets from liver biopsies. It uses self-supervised deep neural networks to learn without human supervision, reducing complex data into simpler core elements that can be understood and collaborated on by humans. This helps in building detailed atlases from genes to cells to tissues to organs and whole patients.
What is the ultimate goal of the speaker's research and the use of AI in medicine?
-The ultimate goal is to create a society of healthy 100-year-olds where people can live longer, healthier lives. The speaker hopes that their research and the use of AI will help in developing therapies that can repair organs like the liver, potentially eliminating the need for transplants.
Outlines
🔬 Advanced Liver Preservation Technology
The script introduces a cutting-edge medical device named Betty, capable of keeping a human liver alive outside the body for an extended period, initially for one day but being developed to last up to five days. This technology is utilized in a unique Intensive Care Unit (ICU) for organs, specifically livers, where scientists, technologists, and clinicians work on enhancing liver preservation. The purpose is to assess liver health before transplantation. The narrative also delves into the innovative use of RNA medicine, which is programmed to target specific cells within the liver, marking a new approach to liver treatment. The speaker shares a personal connection to liver disease and emphasizes the importance of liver health, citing statistics about liver disease prevalence and the challenges of liver transplant waiting lists.
🧬 Rethinking Medicine Development for Liver Scarring
The speaker discusses the traditional process of developing therapies for liver scarring, which involves hypothesis generation, testing on animals, and eventually clinical trials in humans. This process is time-consuming, expensive, and often results in failure. The speaker criticizes the reliance on animal models for predicting human responses and the inefficiency of lengthy clinical trials. To address these issues, the speaker's team is employing a new approach that includes the use of AI algorithms to analyze large datasets from liver biopsies, aiming to understand liver function and dysfunction at a detailed level. This method is compared to the work of artists who simplify complex scenes into core elements, illustrating a similar approach to simplifying complex biological data.
🛠️ Human Models and AI for Liver Therapy Development
The script explains the team's innovative methods for creating human liver models to test hypotheses and develop therapies. They use a combination of bottom-up and top-down approaches, involving detailed analysis of liver biopsies and the creation of miniature liver models. These models are then used to test potential therapies, with the goal of repairing liver function outside the body and potentially eliminating the need for transplants. The process is accelerated by using AI to analyze data and make predictions, which helps to quickly identify promising therapeutic targets. The speaker highlights the success of this approach in significantly reducing the time and cost associated with traditional drug development methods.
🌐 Vision for Global Organ ICUs and Transformative Medicine
The speaker concludes with a vision of a future where organ ICUs are commonplace, not just for livers but for other organs like kidneys, hearts, and lungs. This vision includes the rapid development and testing of therapies without the long wait times associated with current methods. The hope is that these advances will allow for the transformation of millions of lives by improving organ health and potentially eliminating the need for organ transplants. The speaker emphasizes the importance of this work in the face of an aging population and the increasing prevalence of chronic diseases.
Mindmap
Keywords
💡Liver Intensive Care Unit (IU)
💡RNA Medicine
💡Chronic Diseases of Aging
💡Aging Epidemic
💡Self-Supervised Deep Neural Network
💡Hypothesis Generation
💡Clinical Trials
💡Human Data
💡AI Avatar Human Liver Models
💡Organ ICU
Highlights
Introduction of Betty, a machine that can keep a human liver alive outside the body for a day.
Betty is used in the clinic to assess liver health before transplant.
The liver Intensive Care Unit (ICU) is a unique setting where the 'patient' is an organ.
Use of RNA medicine to modify the behavior of specific genes in the liver.
Aim to reprogram donor organs that are too old or diseased for transplantation.
Personal story of the speaker's early stages of liver disease and its unnoticed symptoms.
One in three people may have a liver similar to the speaker's, highlighting the prevalence of liver disease.
The grim reality of liver transplant waiting lists and the high mortality rate.
Projections of increased life expectancy and the implications for organ health and chronic diseases.
The concept of an 'aging epidemic' and its potential parallels to global warming.
The use of sibling mice from a lab to demonstrate the effects of a treatment that removes age-accumulated cells.
The need to rethink medicine as not just curing disease but maximizing health span.
The challenges in creating transformative medicines for chronic diseases of aging.
The three-step process of creating a therapy: idea generation, hypothesis testing, and clinical trials.
The limitations of traditional methods like animal models and the high failure rate of clinical trials.
The innovative approach of using AI and deep neural networks to understand liver function.
Building detailed atlases from genes to cells to tissues to organs for a comprehensive understanding.
The development of human liver models to test hypotheses and therapies more efficiently.
The potential of these models to reduce the time from idea to human data on a new therapy from years to days.
The role of computational models and AI in predicting successful therapies and accelerating the development process.
The vision of organ ICUs worldwide for advanced organ preservation and therapy testing.
The speaker's hope for the transformative impact of this science on millions of lives.
Transcripts
[Music]
so let's speak about the elephant in the
room this is Betty everyone say hello to
Betty Betty oh they respond this is this
is fantastic uh this is a machine that
can keep a human liver alive outside of
the Body for a day it's really cutting
edge technology the surgeons are already
using in the clinic to assess how well
livers are doing before transplanting
into another human being this is our
liver Intensive Care Unit or IU in
downtown Manhattan here are a very
talented team of scientists
technologists and clinicians are
modifying how we use those five liver
machines to keep livers alive not just
for one day but five days this is a very
different kind of ICU where the patient
is an
organ so why are we doing this
each one of our livers gets injected
with a vial of white powder like this
this is an RNA medicine not exactly like
the co RNA vaccines you'll be familiar
with this is more
sophisticated this medicine is
programmed not only to change the
behavior of any Gene that we want it's
also programmed to only go to very
specific cells in the liver you're
looking at what is in effect a new way
of thinking about liver medicines Where
We Are reprogramming donor organs that
are too old too disease to go to the
patients who really need them why are we
doing the liver
though this is a picture of my
liver not pretty is
it a healthy liver doesn't look quite so
pale or so plump and that's because I
have early stages of liver disease now
you can't tell by looking at me and I
feel absolutely fine and I will keep
feeling absolutely fine I promise for
many many years until at some stage my
liver May scar so badly that it will
fail and when it fails my only option
will be a liver
transplant are you ready for a very
scary
statistic I'm going to ask everybody in
this room to look to the person on your
left are they're so interact oh they
love the audience participation here and
then to your
right no your other
left
one in three of you has a liver that
looks like mine and the sad reality is
that if you end up on a liver transplant
waiting list there is a good chance that
you will die before a healthy enough
liver is found for
you ready for another
statistic one in six of us in many parts
of the world born now can expect to live
to be a hundred what will these healthy
100y olds mostly be dying of cancer
infections no the wear and tear of old
age and disease exactly what's happening
with my
liver Hearts kidneys failing after years
of high blood pressure bones crumbling
joints degrading breathing becoming
difficult after a lifetime of pollution
we call these chronic diseases of Aging
in fact many times we really just mean
it's your parts wearing
out and this isn't a problem we've
always had to face right as a species in
the Middle Ages lucky was reaching in
your mid-30s now lucky is almost three
times that in 30 years time one in four
of us are going to be over the age of 60
and I guarantee you will be expecting
your parts to be living much longer than
they ever
have we are beginning to approach what
some of us refer to as an aging epidemic
and many of us believe could be as
important as global
warming so what do we do how do we
create a society of healthy 100 Ys where
your 60s are about that second career
that you've always wanted and not
retiring what's that real change that we
need you're looking at sibling Mice from
a lab and Mayo Clinic
they are the same age the one on the
left is showing its real age whereas the
one on the right still looks young and
healthy this young one has been given a
treatment that removes unwanted cells
that tend to accumulate with age think
of it as cleaning the rust out of its
mousy
Parts incredible results like this are
really forcing us to I think rethink
what medicines mean to us not just
agents for curing disease but agents for
maximizing Health span this is the real
change that many are advocating for but
I don't believe this is
enough while I do believe it's very
important that we think hard about the
kind of medicines we'd like to make I
believe it's equally important that we
rethink how we make medicines and it's
that belief that brings me here on a
stage standing next to
Betty let me
explain let's say
you want to make a therapy you want to
make a medicine that reduces scarring in
human livers roughly speaking there are
three steps step one this is the ideas
phase this is where we call this
hypothesis generation where you come up
with those that list of genes that you
think could affect scarring and which
could be targets for your
therapy how do we do this well
traditionally one one method has just
been reading a lot of papers looking at
what university scientists play with we
call this the Street Lamp approach
because it's a little like searching for
your lost Keys only near Street lamps
because that's where the light
is thankfully a lot of scientists have
now come together to build incredible
databases like the UK bio bank that has
the genetic and disease information for
half a million
people these databases are definitely
helping illuminate a lot more but the
sad reality is they don't help us
understand a lot about the fun
fundamentals of what our internal organs
are
doing there is so much about liver
function and dysfunction that we just
don't understand and without this
knowledge it becomes very difficult to
make a medicine bringing us to step two
which is test your hypothesis and make a
medicine simple no this stage lasts many
many years I ofer a decade or more
here's the rub we of course can't
experiment in human beings so we do a
lot of work in animals we poison mice we
actually perform very cruel surgeries on
them to make the live a scar all the
while knowing that this is very poorly
predictive of what we can expect in
human beings mice only live for about
two years whereas the scarring we're
talking about can build up over decades
if I'm to be very honest with you about
the mice that I showed you we have no
idea if we'll achieve the same result in
longer lived humans the reality is we
have cured so so many diseases in our
road and friends only to find out that
these therapies are effectively useless
by the time we reach step three which is
Testo therapy in a human
being here's the problem with clinical
trials for chronic diseases of
Aging they take very long are very
expensive and usually
fail you can spend easily $100 million
doing this kind of scarring trial
only to find out the mice got it very
wrong isn't that crazy no wonder it is
so difficult to make the kind of
transformative medicines that we need so
that you can look forward to your
60s so what do we do then well we solve
this by taking on the challenges in
those three steps we don't know enough
human biology we're overly reliant on
animal models and clinical trials that
are too long too expensive and too high
risk
this is the challenge the team and I set
ourselves when we decided to make
medicines in a very different way and
I'd like to walk you through just the
first Two
Steps step one learn about how the liver
actually works at
scale to do this we've set up labs in
Europe Asia and the us where we are
sequencing and studying livers in
incredible
detail here's one example of how we do
things you're look looking at an image
of a biopsy this is a biopsy from a
single liver one of a thousand livers
that we studied in the
UK we take that image and we break it up
into the smaller images you see there we
then feed those images into an AI
algorithm that we call a self-supervised
deep neural network this algorithm can
learn without human
supervision and when it does that it's
able to paint an image like this
this image this abstraction is how the
algorithm is actually making sense of
very big very complex data across very
many livers is taking all of that and
reducing it down to what it sees as
simpler core
elements this is very similar to how
artists such as mandrian looked at the
world around them and reduced it to
simpler core
elements this is mandan's depiction of
New York City
which has famously been hanging upside
down all of these years it's pretty
obvious which way up is
no our algorithm does exactly this it
takes very big ideas and reduces it down
to something that simpler human Minds
can collaborate with and we're doing
just that so for example that element
over there is something that we
recognize as fat buildup inside the
liver which I'm showing you here is the
light Parts in this biopsy
we can also map these elements to every
Gene and here I'm showing you the very
beautiful spatial expression of one gene
in green we then can map all of these to
Patient traits and we've done that for
blood patient histories uh and even
General features like body weight in
doing this we're building up very
detailed atlases from genes to cells to
tissue to organs and then whole patients
but that's not enough we want to be able
to test our hypotheses step two in human
models our lab and Ox takes a bottom up
approach and by that I mean we take lots
of different types of cells from
different donor livers and we bring them
back together to build little models of
what we see as liver function and
dysfunction our lab in taipe takes a
more top- down approach this is the only
lab in the world that has set up a
clinical Network to receive biopsies
from disease livers turning each biopsy
into about 50 slices and then culturing
culturing these slices in the lab as
many diseased
microl using these approaches we're
learning a lot about human biology and
making therapies to change the biologies
that we see bringing us to the final
stage that is testing our Therapies in
whole human livers here we look at how
we can improve the function in the
livers so in effect during the clinical
trial before the clinic
trial here's a really cool thing so yes
we are repairing livers outside of the
body but remember I said to you that
these medicines are programmed to go to
certain cells in the liver that's
because once we've learned how to do
that these medicines become a shot in
the arm of patients with liver disease
going directly to their livers to repair
their livers inside their body hopefully
one day doing away with the need for
transplant all
together here's another really cool
thing so remember I said that step two
from ideas to step three clinical trials
that part often takes 10 years or more
using these kind of approaches we're
able to go from Step One to a new
therapy to generating human data on a
new therapy in days not yours so sure I
mean I will agree these aren't perfect
models no model ever is but what this is
helping us to do is learn to fail fast
so that we can be a lot more sure about
the therapies we want to take forward to
step
three I want to share one more thing
that I think is super cool so we're not
just generating a lot of data genes and
cells and livers we're actually building
computational models our goal here is
that AI Avatar human liver models make
such good predictions that they start
helping our scientists come to the right
conclusion even quicker and we're doing
just that so this is actual data from
our
lab here I'm showing you the low success
rate you can expect using traditional
experimental approaches so if we take
randomly take genes we take 100 genes
250 genes and then 500 genes at most we
can expect to capture about just over 3%
of the really interesting genes out
there if we take these experimental
results the data and feed it back to an
algorithm the algorithm can have a look
at what's worked and what hasn't and
then make suggestions about which genes
we really want to be looking at when we
do that and go back to the lab our
success immediately jumps
up so in a single step from humans
talking to algorithms talking back to
humans we've already dramatically
increased our success and crucially at a
fraction of the price it would have cost
us if we just used traditional
experimental approaches what I really
like about this kind of story is that in
an age where frankly I feel there's a
lot of hype around AI what it will do
and how it might Supply to all of us
we're coming to a more pragmatic
conclusion that algorithms and humans
actually make for really great
collaborators and it's this lesson that
I believe has very deep implications
Beyond just chronic liver disease to
other diseases so for example machines
exist s that not only keep your liver
alive but kidneys heart
lungs imagine when one day this is not a
liver ICU but an organ
ICU imagine these organ icus all over
the world where donor organs that AR
transplanted can
go imagine scientists being able to
really form ideas and quickly test out
therapies without having to wait for
years the current hope in transplant
medicine is that each one of your organs
may get to save
aif my hope with this kind of science is
that the gift of my organs will get to
transform millions of lives thank
you
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